ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: PROJECT NARRATIVE  A class of drugs known as mTOR antagonists has recently emerged as a promising treatment for epilepsy, but these antagonists are not effective in all patients, and preclinical studies have found mixed effects in models of epilepsy. We hypothesize that the utility of these drugs is limited because they have opposing effects in excitatory and inhibitory brain cells - they restrict abnormal growth of excitatory cells, which limits epilepsy, but they also restrict the growth of inhibitory cells, which makes epilepsy worse. We propose a series of experiments that will test this hypothesis that, if correct, will provide new guidance on how to develop and improve the efficacy of this promising drug class.

PI_NAMEs: DANZER, STEVE C (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: acquired epilepsy;Adaptor Signaling Protein;Affect;Animal Model;Animals;antagonist;Anticonvulsants;Antiepileptogenic;arm;Benchmarking;Bilateral;Brain;brain cell;calmodulin-dependent protein kinase II;cell growth;Cells;Clinical;Dependovirus;design;Development;Disease;disease model;Enterobacteria phage P1 Cre recombinase;Epilepsy;Epileptogenesis;excitatory neuron;experience;experimental study;Feedback;FRAP1 gene;Frequencies;Genetic;genetic approach;Genetic Models;genetic regulatory protein;Goals;Growth;Hippocampus;Impairment;improved;improved outcome;inhibitor;inhibitory neuron;Injections;innovation;Interneuron function;Interneurons;Kainic Acid;LoxP-flanked allele;Metabolism;Modeling;Mus;Mutation;National Institute of Neurological Disorders and Stroke;Neurons;neuroprotection;Parvalbumins;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Phenotype;Pilocarpine;preclinical study;prevent;preventable epilepsy;Preventive treatment;Process;promoter;protective effect;recombinase;Reporter;Rodent;Rodent Model;Role;SDZ RAD;Seizures;Series;Severities;Signal Transduction;Sirolimus;Somatostatin;Testing;Transgenic Organisms;Tuberous Sclerosis;United States;vector;vesicular GABA transporter

PROJECT_TITLE: Anti-epileptogenic role of mTOR activation among hippocampal interneurons

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: HANOVER

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PI_NAMEs: FIERING, STEVEN  (contact)

PROJECT_TERMS: Alleles;Antibodies;Area;Award;Biology;Biomedical Research;Breast Adenocarcinoma;Breast Cancer Model;Budgets;Cancer Center;Cancer Center Support Grant;Communicable Diseases;Communities;Complex;cost effective;CRISPR/Cas technology;embryonic stem cell;Engineering;Experimental Designs;Experimental Models;experimental study;Faculty;flexibility;Funding;Gene Modified;Generations;Genes;Genetic;Genetically Engineered Mouse;Glioma;Human;Human Resources;ID2 gene;Knock-in;LoxP-flanked allele;Maintenance;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;member;model organism;Modeling;Modification;mouse model;Mus;NCI Center for Cancer Research;Neurosciences;Norris Cotton Cancer Center;Nursing Faculty;Pathologic;Phosphotransferases;programs;Reporting;Research;Research Personnel;Resource Sharing;Resources;Role;Schools;Services;skills;Solvents;Technology;Time;tissue culture;Update;Work;zygote

PROJECT_TITLE: Mouse Modeling (MM)

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Cancer Centers Study Section (A)[NCI-A]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_CITY: Newark

ORG_DEPT: PSYCHIATRY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE Cocaine addiction is a chronic condition that remains clinically difficult to treat. The proposed studies will reveal the role of a key brain neuropeptide system in the persistent, chronically relapsing nature of cocaine addiction. These findings will increase our knowledge of brain mechanisms involved in chronic addiction, and test a novel method for treating this disorder using a currently approved medication.

PI_NAMEs: ASTON-JONES, GARY S. (contact)

PROGRAM_OFFICER_NAME: MOORE, HOLLY MARIE

PROJECT_TERMS: Abstinence;Acute;addiction;Animals;antagonist;Area;Bacterial Artificial Chromosomes;Behavior;Brain;Cell Count;Cells;Chronic;Clinical;Cocaine;Cocaine Dependence;cocaine seeking;cocaine self-administration;cocaine use;Cues;Data;Development;Disease;Drug abuse;drug of abuse;Drug usage;Dynorphins;Economics;endophenotype;Exhibits;experimental study;Extinction;FDA approved;Fiber;genetic approach;hypocretin;Hypothalamic structure;Inferior Colliculus;Knowledge;Label;Lateral;Link;Medial;melanin-concentrating hormone;Methods;Modeling;Motivation;Nature;nerve supply;Neurons;Neuropeptides;novel;orexin 1 receptor;Pattern;Peptides;Pharmaceutical Preparations;Phenotype;Play;prevent;Punishment;Rattus;receptor;Receptor Signaling;Relapse;Resistance;reward processing;Rewards;Role;Self Administration;Signal Transduction;Site;Structure of paraventricular nucleus of thalamus;System;Testing;Thalamic structure;Transgenic Organisms;Ventral Tegmental Area

PROJECT_TITLE: ROLE OF OREXIN IN COCAINE DEMAND AND ADDICTION

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Diabetes;Genetics;Nutrition;Obesity

ORG_CITY: ANN ARBOR

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Emerging genetic evidence in humans has linked various Wnt pathway members to body fat distribution, obesity, and metabolic dysfunction, suggesting that this pathway is operative in terminally-differentiated adipocytes. Indeed, our recent studies in mice have uncovered compelling evidence suggesting that the Wnt pathway plays important roles in adipocyte metabolism, particularly under obesogenic conditions. Successful completion of our proposed experiments will improve our understanding of how this ancient signaling pathway is critical for the physiology and pathophysiology of adipose tissues.

PI_NAMEs: MACDOUGALD, ORMOND A (contact)

PROGRAM_OFFICER_NAME: GUPTA, DHANANJAY

PROJECT_TERMS: ADD-1 protein;adipocyte differentiation;Adipocytes;Adipose tissue;Affect;ATAC-seq;Back;beta catenin;Binding;Bioinformatics;blood glucose regulation;Blood Vessels;Body fat;Cardiovascular Diseases;Cell Nucleus;Cell Physiology;cell type;Cells;chromatin immunoprecipitation;Chronic Disease;Compensation;Complex;CTNNB1 gene;Data;Dedications;Diet;diet-induced obesity;DNA Binding;Enhancers;Enzymes;Evaluation;Exhibits;experimental study;extracellular vesicles;FABP4 gene;fatty acid metabolism;Fatty Acids;Felis catus;flexibility;Fluorescence-Activated Cell Sorting;Functional disorder;Gene Expression;Genetic;Genetic study;Genetic Transcription;Glycolysis;High Fat Diet;Homeostasis;Human;Human Genetics;Hypertrophy;Impairment;improved;in vivo;infancy;Inflammatory;inhibitor;Insulin Resistance;Investigation;Knockout Mice;LDL-Receptor Related Protein 1;Ligands;Link;lipid biosynthesis;lipid metabolism;Low Density Lipoprotein Receptor;Lymphoid;Mediating;member;Membrane;Mesenchymal;Messenger RNA;Metabolic;Metabolic dysfunction;Metabolic Pathway;Metabolism;Molecular;Molecular Chaperones;Monitor;Monounsaturated Fatty Acids;Mus;Non-Insulin-Dependent Diabetes Mellitus;Nutritional;Obese Mice;Obesity;obesogenic;Overnutrition;Oxidative Phosphorylation;Pathway interactions;Phenotype;Physiological;Physiology;Play;Population;Production;Proliferating;promoter;Protein Secretion;Proteins;receptor;Regulation;Reporting;Repression;Resistance;response;Risk Factors;Role;Signal Pathway;Signal Transduction;Signaling Molecule;Signaling Protein;single-cell RNA sequencing;Stromal Cells;System;TCF Transcription Factor;Testing;Tissues;Up-Regulation;Wnt proteins;WNT Signaling Pathway;Work

PROJECT_TITLE: Effects of Wnt/β-catenin signaling on adipocytes


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Orphan Drug;Precision Medicine;Rare Diseases

PI_NAMEs: TSONGALIS, GREGORY JAMES (contact)

PROJECT_TERMS: Accreditation;Acute Myelocytic Leukemia;Adult;biobank;Biological Assay;Biological Markers;biomarker development;biomarker discovery;Budgets;Cancer Center Support Grant;cell free DNA;Cell Therapy;Childhood;CLIA certified;Clinical;Clinical Data;Clinical Trials;Computer software;Data;data mining;data warehouse;Databases;design;Environment;Funding;fusion gene;Gastrointestinal Stromal Tumors;Gene Mutation;gene panel;gene therapy;Genes;genomic data;Genomics;Glioma;Histology;Human;Immunofluorescence Immunologic;Institution;Ions;Laboratories;Malignant Neoplasms;Medicine;member;metastatic colorectal;Metastatic Melanoma;multidisciplinary;Mutation;Myelogenous;next generation sequencing;Non-Small-Cell Lung Carcinoma;Norris Cotton Cancer Center;Oncogenes;Pathology;Patients;personalized medicine;Physicians;programs;Publications;Research;research clinical testing;Research Personnel;Resource Sharing;Role;Sampling;Sarcoma;Scientist;Services;Solid Neoplasm;Somatic Mutation;Specimen;System;targeted treatment;Technology;Testing;Translational Research;triple-negative invasive breast carcinoma;tumor

PROJECT_TITLE: Pathology (PSR)


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Bioengineering;Clinical Research;Data Science;Emergency Care;Lung;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Rare Diseases

ORG_CITY: DAVIS

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PI_NAMEs: ADAMS, JASON YEATES;CALLCUT, RACHAEL A;STROHMER, THOMAS  (contact)

PROGRAM_OFFICER_NAME: SHENOY, SIDDHARTH KAUP

PROJECT_TERMS: Accident and Emergency department;Acute Respiratory Distress Syndrome;Acute respiratory failure;Address;Admission activity;Advanced Development;Affect;algorithm development;Algorithms;American;Architecture;Area;Artificial Intelligence;Benchmarking;care costs;Caring;Cessation of life;Clinical;clinical application;clinical decision support;clinical development;clinical practice;clinically relevant;cohort;complex data;cost;cost efficient;Critical Care;Critical Illness;Data;data framework;data privacy;Data Protection;data quality;Data Set;Detection;Development;Diagnosis;Discrimination;Effectiveness;Electronic Health Record;Ensure;Evaluation;Evolution;experience;Failure;Functional disorder;Generations;Goals;Health;health data;Healthcare;high risk;Hospitals;Housing;Image;improved;innovation;Instruction;Interdisciplinary Study;Intubation;Laboratories;Laws;Lung;Machine Learning;Manuals;Mathematics;Mechanical ventilation;Medicine;Methodology;Methods;Modality;Modeling;Morbidity - disease rate;mortality;multimodal data;multimodality;novel;Operating Rooms;Patients;Perception;Play;Privacy;privacy preservation;Property;psychologic;Research;respiratory;Respiratory Failure;Risk;Societies;Statistical Methods;Syndrome;synthetic data;Techniques;Testing;theories;Time;tool;Transportation;Treatment outcome;Validation

PROJECT_TITLE: SCH: Heterogenous, dynamic synthetic data: From algorithms to clinical applications

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-VH-N(50)R]


NIH_SPENDING_CATS: Cancer

PI_NAMEs: JACKSON, BRIAN P (contact)

PROJECT_TERMS: analytical method;Animal Organ;animal tissue;Arsenic;Beverages;bioimaging;Biological;Blood;Budgets;Cancer Center;Cancer Center Support Grant;Carcinogens;case-by-case basis;Catchment Area;Cells;Cereals;Chemicals;Chromatography;Coupled;Data;early life exposure;Elements;Ensure;Exposure to;Fishes;Funding;granite;Hair;Health Policy;Human;Individual;Inductively Coupled Plasma Mass Spectrometry;Infant;Inorganic Chemistry;Institution;instrument;instrumentation;International;Invertebrates;Iron;Link;Malignant Neoplasms;Measures;member;Methods;Micronutrients;Monitor;nanoparticle;NCI Center for Cancer Research;Norris Cotton Cancer Center;Placenta;Platinum;Play;Population Sciences;Preparation;programs;Protocols documentation;Public Health;quality assurance;Quality Control;Research;Research Personnel;Resource Sharing;Resources;Role;Running;Sampling;Selenium;Services;Soil;Structure of nail of toe;Technology;Testing;Therapeutic Effect;Therapeutic Uses;Tissues;Trace Elements;Urine;Water;Work

PROJECT_TITLE: Trace Elements (TE)


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Chronic Pain;Neurosciences;Pain Research

ORG_CITY: SEATTLE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative This project is expected to broadly address the enormous health care concern chronic pain, which affects greater than 20% of the US population, by elucidating the mechanisms that encode the profound emotional suffering associated with this disease. Dysregulation of aversive motivational circuits may underlie much of the suffering associated with chronic pain conditions. This research is relevant to NIH's mission, as it will identify pathways to selectively block the generation of aversive motivation in response to painful stimuli and potentially create a path forward for the development of novel therapeutics for the treatment of chronic pain.

PI_NAMEs: DHAKA, AJAY K (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Ablation;Address;Affect;allyl isothiocyanate;Analgesics;antagonist;Automobile Driving;Aversive Stimulus;Behavioral;Biological Models;Chemicals;chronic pain;chronic pain management;chronic painful condition;Complex;Darkness;Data;Development;Diffuse;Disease;Dopamine;Dopamine D1 Receptor;Dose;Emotional;emotional experience;Esthesia;experimental study;Food;Formalin;Gene Deletion;Generations;genetic approach;Healthcare;hedonic;Human;Induced Neurons;Inflammatory;Injections;International;Mammals;Maps;Measurement;Mediating;Mission;Mood Disorders;Motivation;mouse model;Movement;Mus;Negative Valence;Nervous System;neural;neural circuit;neuronal circuitry;Neurons;Neurotransmitters;Nociception;Nociceptive Stimulus;novel;novel therapeutics;Nucleus Accumbens;optogenetics;Pain;pain perception;pain processing;Pathway interactions;Patients;Phase;pleasure;Population;Positive Valence;preference;protective behavior;Receptor Activation;Research;response;Rewards;Role;Sensory;side effect;Signal Transduction;Site;small molecule;small molecule libraries;Stimulus;System;Testing;Therapeutic;Time;Tissues;tool;United States National Institutes of Health;Vertebrates;Zebrafish

PROJECT_TITLE: Identifying new targets in pain, utilizing the novel analgesic AS1

STUDY_SECTION: SPS

STUDY_SECTION_NAME: Somatosensory and Pain Systems Study Section[SPS]


NIH_SPENDING_CATS: Behavioral and Social Science;Breast Cancer;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Lung Cancer;Palliative Care;Prevention;Social Determinants of Health;Women's Health Research

PI_NAMEs: CHRISTENSEN, BROCK CLARKE (contact)

PROJECT_TERMS: advanced disease;Area;Arsenic;Award;Basic Science;Behavioral;Breast Cancer Detection;Cancer Burden;Cancer Center Support Grant;cancer epidemiology;Cancer Etiology;cancer genetics;cancer prevention;cancer risk;Cancer Science;care delivery;Catchment Area;Child;Clinic;Clinical;Clinical effectiveness;Collaborations;colon cancer screening;Data;design;Development;Direct Costs;Discipline;Educational workshop;Electronic cigarette;Epidemiologic Factors;exercise intervention;Faculty;Fostering;Funding;Future;Geography;Goals;Grant;Growth;Health;health care delivery;Healthcare;Heavy Metals;implementation research;improved;Incidence;Institution;Interdisciplinary Study;interest;Intervention;Investigator-Initiated Research;Journals;Life Cycle Stages;lung cancer screening;Malignant Breast Neoplasm;Malignant Neoplasms;Marketing;Medical center;medical schools;meetings;member;Mentors;Mentorship;Metal exposure;microbiome;Molecular;Multicenter Studies;NCI-Designated Cancer Center;new technology;next generation;Obesity;Outcome;Palliative Care;Paper;patient population;Patients;Peer Review;Persons;Physicians;Policies;Polyp Prevention Trial;Population;population health;Population Sciences;Population Study;Poverty;Prevention;Productivity;programs;Publications;Publishing;Quality of Care;Quality of life;Recording of previous events;recruit;Reporting;Research;Research Personnel;Resource Sharing;Risk;Risk Behaviors;Risk Factors;Risk Reduction;Risk Reduction Behavior;Rural;rural patients;Rural Population;Science;Scientist;screening;Screening for cancer;senior faculty;Services;severe mental illness;smoking cessation;State Government;Sum;survivorship;Testing;Tobacco;Training;Training Programs;Travel;United States Department of Veterans Affairs;Vulnerable Populations;well water;Work;working group

PROJECT_TITLE: Cancer Population Sciences (CPS)


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Kidney Disease

ORG_CITY: Aurora

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative Hyperphosphatemia and vascular calcification are major complications in patients with chronic kidney disease (CKD) and are highly associated with mortality. We recently found that a novel driver regulates phosphate balance in the kidney. We will test whether the novel driver can be used as a target for treatment of hyperphosphatemia and vascular calcification in CKD.

PI_NAMEs: BLAINE, JUDITH T.,;MIYAZAKI, MAKOTO  (contact)

PROGRAM_OFFICER_NAME: KETCHUM, CHRISTIAN J

PROJECT_TERMS: absorption;Affect;Apical;Binding;Biology;bone;Brush Border;brush border membrane;calcification;Cardiovascular Diseases;Cardiovascular system;Cause of Death;Cells;cellular microvillus;Chronic Kidney Failure;Clinical Research;Collaborations;Custom;Data;Disease;Doctor of Philosophy;End stage renal failure;Equilibrium;Etiology;Event;Excision;Feedback;fibroblast growth factor 23;Fluorescence;Fluorescence Microscopy;Fluorescence Resonance Energy Transfer;Functional disorder;Genes;Genetic;Heart Hypertrophy;Homeostasis;Hormonal;Human;Image;In Vitro;in vivo;innovation;inorganic phosphate;Inorganic Phosphate Transporter;insight;Intestines;Kidney;Knock-out;Knockout Mice;Libraries;Mediating;Membrane;Methodology;Microscopic;Modeling;Molecular;mortality;mouse model;mRNA sequencing;Mus;Myocardial dysfunction;novel;Parathyroid gland;Pathogenesis;Patients;Proteins;Proximal Kidney Tubules;PTH gene;reconstitution;Regulation;Reporting;Resistance;response;RNA Interference;Role;Scheme;Scientist;screening;Signal Transduction;Small Interfering RNA;Sodium;sodium-hydrogen exchanger regulatory factor;Spectrum Analysis;Testing;transcriptome sequencing;Tubular formation;Ultrafiltration;uptake;Urine;Vascular calcification;Work

PROJECT_TITLE: A Novel Driver of Hyperphosphatemia and Vascular Calcification in CKD

STUDY_SECTION: KMBD

STUDY_SECTION_NAME: Kidney Molecular Biology and Genitourinary Organ Development[KMBD]


PI_NAMEs: GERBER, SCOTT A. (contact)

PROJECT_TERMS: Acceleration;Award;Back;Basic Cancer Research;Basic Science;Biological Models;Biology;Breast;Cancer Biology;cancer cell;Cancer Center Support Grant;cancer diagnosis;cancer initiation;cancer therapy;cancer type;Catchment Area;Cell Cycle;Cellular Metabolic Process;Chromatin;Classification;Clinic;Clinical;clinical application;clinical development;Clinical Research;clinical translation;Clinical Trials;Collaborations;design;Development;Diagnosis;Diagnostic;diagnostic strategy;Direct Costs;Discipline;early phase trial;Exclusion;Extramural Activities;Faculty;Fostering;Funding;Genetic Transcription;Genome Stability;Goals;graduate school;improved;innovation;insight;Institution;interdisciplinary collaboration;Interdisciplinary Study;interest;Invaded;Investigational Therapies;Joints;Journals;Knowledge;Laboratories;Laboratory Finding;Laboratory Scientists;Lung;Malignant Neoplasms;Measures;Medical center;Medical Oncologist;medical schools;member;Mentors;Mentorship;Molecular;Molecular Target;Movement;multidisciplinary;Natural History;NCI Center for Cancer Research;Neoplasm Metastasis;New England;Norris Cotton Cancer Center;novel;novel diagnostics;novel therapeutics;Oncogenic;Pathway interactions;patient population;Peer Review;Physicians;Play;Prevention;Productivity;programs;Publications;recruit;Reporting;Research;Research Activity;Research Personnel;Resource Sharing;Role;Rural;rural patients;Schools;scientific organization;Scientist;Services;Signal Transduction;Sum;Surgical Oncologist;Therapeutic;Therapeutic Intervention;Therapeutic Research;therapeutically effective;Training;translational cancer research;Translational Research;translational scientist;translational study;Translations;Validation

PROJECT_TITLE: Cancer Biology and Therapeutics (CBT)


ED_INST_TYPE: SCHOOLS OF OSTEOPATHIC MEDICINE

ORG_CITY: EAST LANSING

ORG_DEPT: PHARMACOLOGY

ORG_NAME: MICHIGAN STATE UNIVERSITY

PHR: Project Narrative - Overall  The primary goal of this new Program Project Grant application is to create a foundational model for perivascular adipose tissue (PVAT) function in assisting the vasculature to remain healthy, and to understand how PVAT ultimately contributes to the cardiovascular diseases that plague our world. We work to build a more comprehensive and holistic view of the vascular layers, with the idea that such knowledge enables new potential therapeutic approaches that improve vascular health.

PI_NAMEs: WATTS, STEPHANIE W (contact)

PROGRAM_OFFICER_NAME: OH, YOUNGSUK

PROJECT_TERMS: Adipocytes;Adipose tissue;Adult;Affect;Animals;Applications Grants;Arteries;Bioinformatics;Blood capillaries;Blood Pressure;blood pressure regulation;Blood Vessels;Cardiovascular Diseases;Cardiovascular Physiology;Cell Physiology;cell type;Cells;Collaborations;Communication;Communities;Complement;data sharing;Development;Disease;Elements;Excess Mortality;experimental study;Fatty acid glycerol esters;Fibroblasts;fighting;Functional disorder;Genes;genetic approach;Goals;Grant;Health;High Fat Diet;Home;Homeostasis;Human;Human body;Hypertension;Immune;immunoregulation;improved;Inbred Dahl Rats;Individual;Informatics;Investments;Knowledge;Laboratory Animals;Learning;Literature;mechanical force;Mechanics;mechanotransduction;Mesenchymal;Microscopic;Microscopy;model organism;Modeling;Mus;Nature;Nerve;nerve supply;Neurons;novel;novel strategies;Obesity;optogenetics;Pathologic;peripheral blood vessel;Physiological;Physiology;pressure;progenitor;Program Research Project Grants;Publishing;Rattus;Regulation;Research;Research Personnel;response;Scientist;stem cells;stem-like cell;Stretching;synergism;Systems Integration;Testing;Therapeutic;Therapeutic Intervention;Thoracic aorta;Time;Tissues;transcriptome sequencing;translational potential;Tunica Adventitia;vasa vasorum;Vascular Diseases;Work

PROJECT_TITLE: Perivascular Adipose Tissue (PVAT) as a Central Integrator of Vascular Health

STUDY_SECTION: HLBP

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


ADMINISTERING_IC: AT

ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Cerebrovascular;Complementary and Integrative Health;Genetics;Human Genome;Natural Products;Neurosciences;Physical Injury - Accidents and Adverse Effects;Stroke;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative There are currently no FDA-approved medications to treat the neuropathology that follows traumatic brain injury; however, inhibition of cathepsins B and L have been associated with improved neurocognitive and behavioral outcomes after neuronal injury in animal models. Cyanobacteria are known to produce natural product compounds with neurologic bioactivity, including cathepsin and other protease inhibitors. In this proposal, we hypothesize that novel cathepsin inhibitors can be discovered from cyanobacteria through an innovative genomic approach, which includes pharmacophore-based genome mining, delineation of biosynthetic gene clusters, cultivation, and heterologous gene expression.

PI_NAMEs: AVALON, NICOLE ELIZABETH (contact)

PROGRAM_OFFICER_NAME: STILL, PATRICK COLBY

PROJECT_TERMS: Active Sites;Anabaena;Anabolism;analog;Aneurysmal Subarachnoid Hemorrhages;Animal Model;Antibiotic Resistance;Architecture;Atlases;Behavioral;behavioral outcome;Bioinformatics;Biological Assay;Biology;Bypass;Caspase;Cathepsin L;Cathepsins;Cathepsins B;Cells;Cerebral hemisphere hemorrhage;Cerebral Ischemia;Cessation of life;Chemicals;clinical development;Collection;Complex;Cyanobacterium;Data;design;Docking;drug candidate;drug discovery;Drug Targeting;Environmental Impact;Enzymes;experimental study;FDA approved;Fellowship;Gene Cluster;Gene Expression;Genome;Genomic approach;Genomic Library;Genomics;Goals;improved;in silico;In Vitro;inhibitor;Injury;innovation;Institution;interdisciplinary approach;interest;Ion Channel;Ischemia;Knock-out;Lead;Libraries;Literature;markov model;Methods;Mining;Modeling;Molecular;Morbidity - disease rate;mortality;Mus;nanomolar;National Research Service Awards;Natural Products;Neurocognitive;Neurocognitive Deficit;neuroinflammation;Neurologic;Neurological outcome;Neuronal Injury;Neurons;neuropathology;neuroprotection;novel;novel therapeutics;Oceanography;Organism;Outcome;overexpression;Pathway interactions;Pattern;Peptide Hydrolases;peptide natural products;peptide synthase;Peptides;Permeability;Pharmaceutical Preparations;Pharmacologic Substance;Pharmacology;pharmacophore;Phylogeny;Plasmids;polyketide synthase;polyketides;post-doctoral training;Postdoctoral Fellow;pre-clinical;prevent;professor;prognostic;Protease Inhibitor;Proteins;Reporter;resistance gene;Ribosomes;Scheme;Secondary to;small molecule;Source;Specificity;Structure;synergism;tandem mass spectrometry;Techniques;Technology;Testing;tool;Traumatic Brain Injury;Tubulin;United States;United States National Institutes of Health;virtual;yeast two hybrid system

PROJECT_TITLE: A Genomic Approach to Discovering Novel Cathepsin Inhibitors from Cyanobacteria


PROJECT_TITLE: Core A (Administrative Core)

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


PI_NAMEs: PAULSEN, KEITH D. (contact)

PROJECT_TERMS: Acceleration;Advocate;anti-cancer research;Articulation;Award;base;Biomedical Engineering;Biophotonics;Biophysics;Brain;Breast;cancer care;Cancer Center;Cancer Center Support Grant;Cancer Detection;Cancer Patient;Cancer Research Project;Capital;Catchment Area;Clinical;Clinical Investigator;Clinical Oncology;clinical practice;Clinical Research;Collaborations;Computational Science;computer science;design;Detection;Development;Diagnosis;Direct Costs;dosimetry;Engineering;Environment;Evaluation;Exclusion;Extramural Activities;Faculty;Faculty Recruitment;Fostering;Funding;Future;Goals;graduate school;Grant;Head and neck structure;Health;Image;Image Enhancement;image guided;Image-Guided Surgery;imaging facilities;imaging modality;improved;Industry;industry partner;innovation;Institution;interdisciplinary collaboration;interest;Intervention;Investments;Journals;Laboratories;Legal patent;Malignant Neoplasms;Medical;Medical center;Medical Oncology;medical schools;Medicine;member;Mentors;Mission;Molecular;Monitor;multidisciplinary;new technology;Norris Cotton Cancer Center;novel;Operative Surgical Procedures;Pancreas;Pathology;Peer Review;Physicians;Physics;Point of Care Technology;Postdoctoral Fellow;pre-doctoral;Procedures;Program Development;programs;Prostate;Protocols documentation;Publications;Radiation Monitoring;Radiation Oncology;Radiation therapy;Radiology Specialty;Research;research faculty;Research Personnel;Research Project Grants;Resources;Rural;Schools;Services;Skin;Specialist;success;Sum;Surgical Oncology;Surgical Specialties;Technical Expertise;Technology;Technology Assessment;technology development;Testing;Training;Translating;translational goal;Translations;Work

PROJECT_TITLE: Translational Engineering in Cancer (TEC)


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Congenital Structural Anomalies;Hypertension;Nutrition;Pediatric

PI_NAMEs: LAUVER, DALE ADAM (contact)

PROJECT_TERMS: Adipocytes;Adipose tissue;Anatomy;Animal Experimentation;Animal Husbandry;animal imaging;Animal Model;animal resource;Animals;Aorta;Aortic coarctation;Blood Pressure;Blood Pressure Monitors;Blood Vessels;Body Weight;Cardiovascular Physiology;Cardiovascular system;Catheters;Chronic;Complement;Conscious;Cryopreservation;Data;design;Development;Devices;Diet;dietary control;Educational process of instructing;Educational workshop;Elements;Embryonic Development;Ensure;Excision;Fatty acid glycerol esters;Frequencies;Glucose;Goals;Harvest;Health;hemodynamics;High Fat Diet;Human Resources;Hypertension;hypertensive;immunodeficiency;Implant;implantation;In Vitro;in vivo;in vivo imaging system;instrument;instrumentation;interest;Measurement;Measures;Mesentery;Metabolic;Michigan;microCT;Modeling;Monitor;Mus;normotensive;Obesity;Operative Surgical Procedures;organizational structure;pharmacologic;Phenotype;physiologic model;Physiological;Plasma;preservation;Production;programs;Protocols documentation;Rat Strains;Rat Transgene;Rattus;Research;Research Personnel;Resources;Services;subcutaneous;Systolic Pressure;Tail;Techniques;telemetering;Telemetry;Thoracic aorta;Thymectomy;Time;Tissue Banks;Tissue Sample;Tissues;Training;Transgenic Animals;Transgenic Mice;Transgenic Organisms;ultrasound;Universities;Visceral;Whole Blood

PROJECT_TITLE: Core B (Animal Core)


NIH_SPENDING_CATS: Cancer;Immunotherapy

ORG_CITY: PHILADELPHIA

ORG_NAME: WISTAR INSTITUTE

ORG_STATE: PA

PHR: Narrative This proposal addresses in preclinical setting an important clinical problem – tumor escape from immune therapy. We will investigate the basic mechanism of this phenomenon associated with the induction of ferroptosis, a program of regulated cell death. We will test this novel mechanism and its correction in relevant mouse models and determine its clinical relevance using de-identified samples from patients with lung, colon, and pancreatic cancer.

PI_NAMEs: KAGAN, VALERIAN E;NEFEDOVA, YULIA  (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Address;Affect;Alcohols;Apoptosis;Arachidonate 15-Lipoxygenase;Biology;Blood;bone circulation;Bone Marrow;Cancer Patient;Cell Death;Cell Differentiation process;Cell Physiology;Cells;Clinical;clinically relevant;Colon Carcinoma;Cross Presentation;Data;Dendritic Cells;Down-Regulation;Generations;Glutathione;glutathione peroxidase;Goals;granulocyte;Immune;Immune response;immunoregulation;Immunosuppression;Immunotherapy;improved;Iron;Knowledge;Lipid Peroxidation;Lipid Peroxides;Lipids;lymphoid organ;Macrophage;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;monocyte;mouse model;Mus;Myelogenous;Myeloid Cells;Myeloid-derived suppressor cells;Natural Killer Cells;Necrosis;Neoplasm Metastasis;neutrophil;novel;novel strategies;oxidation;oxidized lipid;Pathologic;Patients;peripheral lymphoid organ;Peroxidases;phospholipid-hydroperoxide glutathione peroxidase;Physiological;Population;pre-clinical;programs;Regulation;repaired;Role;Sampling;Signal Transduction;Spleen;System;T cell response;T-Lymphocyte;Testing;Therapeutic;Therapeutic Effect;therapeutic target;treatment effect;tumor;Tumor Escape;tumor microenvironment;tumor progression;Tumor Tissue

PROJECT_TITLE: Therapeutic targeting MDSC-mediated immune suppression in cancer

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


NIH_SPENDING_CATS: Bioengineering;Genetics;Human Genome;Hypertension;Networking and Information Technology R&D (NITRD)

PI_NAMEs: BHATTACHARYA, SUDIN  (contact)

PROJECT_TERMS: Adipose tissue;Animals;Bioinformatics;Biological;Blood Vessels;Cell model;cell type;Cells;Communication;Computer Models;computerized tools;Cost Savings;Data;Data Analyses;Data Set;data visualization;Development;Diet;Disease;Educational workshop;experimental study;Generations;Genes;Genetic Transcription;Genome Data Analysis Network;genomic data;Goals;Health;Health Transition;High Fat Diet;Hour;Human Resources;Hypertension;hypertensive;immune function;in silico;Individual;Informatics;Maps;mechanical force;member;Modeling;Neighborhoods;nerve supply;Nervous System;novel;Onset of illness;open source;Pathway Analysis;Play;pressure;Program Research Project Grants;Regulator Genes;Reproducibility;Research Personnel;response;Role;Services;Signal Transduction;single cell genomics;single-cell RNA sequencing;Testing;theories;Tissues;tool;Training;transcriptome sequencing;Visualization;Visualization software;web portal

PROJECT_TITLE: Core C (Informatics and Computation Core)


NIH_SPENDING_CATS: Biotechnology;Cancer;Immunotherapy

PI_NAMEs: TURK, MARY JO  (contact)

PROJECT_TERMS: Address;Advanced Development;Advocate;Antitumor Response;Applications Grants;Area;Award;bench to bedside;Cancer Biology;Cancer Center;Cancer Center Support Grant;cancer immunotherapy;Cancer Patient;cancer therapy;CAR T cell therapy;career;Cellular biology;chimeric antigen receptor T cells;Clinical;Clinical Research;Clinical Trials;Collaborations;Development;Direct Costs;drug efficacy;engineered T cells;Engineering;Ensure;Equipment;Exclusion;Faculty;Fostering;Funding;Future;Goals;Grant;Health;Health system;Human;Image;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;Immune system;Immunologics;Immunologist;Immunology;immunoregulation;Immunotherapeutic agent;Immunotherapy;immunotherapy clinical trials;improved;innovation;Institution;interest;Intervention;Journals;Laboratories;Laboratory Finding;Leadership;Ligands;Malignant Neoplasms;medical schools;meetings;member;Mentors;Mentorship;Mission;Modality;Molecular;mosaic;novel;Patients;Peer Review;Population Sciences;pre-clinical;programs;Publications;Radiobiology;recruit;Research;Research Personnel;Research Support;Resources;Schools;Scientist;standard of care;success;Sum;T memory cell;T-Lymphocyte;Therapeutic;therapeutic nanoparticles;Training;Translating;translational immunology;tumor immunology;tumor microenvironment;United States National Institutes of Health;viral nanoparticle;Work;working group;Writing

PROJECT_TITLE: Immunology and Cancer Immunotherapy (ICI)


NIH_SPENDING_CATS: Autoimmune Disease;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Genetics;Human Genome;Liver Disease;Machine Learning and Artificial Intelligence;Rare Diseases

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE We will conduct the first multi-omics translational study of primary biliary cholangitis (PBC), to improve understanding of the culprits driving this rare, autoimmune liver disease. By integrating multiple layers of omics data, we will better define the architecture of cellular networks driving PBC. In so doing, we will identify molecular signatures including immune alterations, environmental toxins, and metabolism-related chemicals unique to PBC patients, thereby spurring improved understanding of PBC pathobiology and identification of novel druggable targets.

PI_NAMEs: LAZARIDIS, KONSTANTINOS N (contact)

PROGRAM_OFFICER_NAME: SHERKER, AVERELL H

PROJECT_TERMS: advanced disease;Architecture;Artificial Intelligence;Artificial Intelligence platform;Autoimmune;Autoimmunity;Automobile Driving;biobank;Biological;Biological Assay;Biology;Blood;Caring;cell free DNA;Cellular Immunity;Chemicals;Clinic;Clinical;clinically relevant;Collection;combinatorial;Cytometry;Data;Development;Dimensions;Disease;Disease Progression;effective therapy;Environment;Evaluation;feature selection;Funding;genomic locus;Genomics;Goals;Hand;Heel;Immune;Immune system;Immunity;improved;Individual;Inflammatory;innovation;insight;Investigation;Knowledge;Liver;Liver diseases;Machine Learning;Mass Spectrum Analysis;Measurement;Measures;Mediating;Metabolic;Metabolism;metabolome;Methods;methylome;Molecular Profiling;multidisciplinary;multiple omics;new therapeutic target;novel;novel strategies;novel therapeutics;Onset of illness;Pathogenesis;Pathogenicity;Pathologic Processes;Pathway interactions;patient oriented;Patients;Peripheral;pharmacologic;Phenotype;Pilot Projects;Positioning Attribute;Primary biliary cirrhosis;Process Assessment;Proteins;Publications;quantum;Questionnaires;Research Design;Resources;response;Risk;Role;Sampling;Severity of illness;Specimen;Statistical Mechanics;Subgroup;System;Testing;Therapeutic;Toxic Environmental Substances;transcriptome;translational study;ultra high resolution;Universities;Work

PROJECT_TITLE: Pathogenesis of Primary Biliary Cholangitis

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


NIH_SPENDING_CATS: Autoimmune Disease;Kidney Disease;Lupus;Rare Diseases

PHR: Research Narrative Immune mediated kidney disease leads to immune complex (IC) deposition in podocytes but it is unknown how podocytes handle ICs. The neonatal Fc receptor (FcRn) plays a key role in correctly sorting and trafficking ICs in other cell types. The goal of this proposal is to examine the role of FcRn in trafficking of ICs to the podocyte lysosome and to determine whether inhibition of the lysosomal response to ICs in podocytes ameliorates immune mediated glomerulonephritis.

PI_NAMEs: BLAINE, JUDITH T., (contact)

PROGRAM_OFFICER_NAME: NIHALANI, DEEPAK

PROJECT_TERMS: Aftercare;Albumins;Animal Model;Antigen-Antibody Complex;Apoptosis;Apoptotic;Biochemical;Biological Response Modifiers;Cathepsins;Cathepsins B;CD8B1 gene;Cell Death;Cell Membrane Permeability;cell type;Cells;Cessation of life;cytochrome c;Cytosol;Degradation Pathway;Dendritic Cells;Deposition;Disease;disease model;Disease Progression;End stage renal failure;Endothelial Cells;Enzymes;Extravasation;Fc Receptor;FOXP3 gene;Functional disorder;glomerular filtration;Glomerulonephritis;glomerulosclerosis;Goals;Health;Histologic;Histology;Human;human model;Imaging Techniques;Immune;Immune Targeting;Immunoglobulin G;Immunological Models;improved;in vivo;in vivo Model;Induction of Apoptosis;insight;interest;Kidney;Kidney Diseases;Kidney Failure;Knock-out;Knockout Mice;Location;Lupus Nephritis;Lysosomes;Macrophage;Mediating;Mediator;Membranous Glomerulonephritis;Methods;Mitochondria;mitochondrial membrane;Modeling;monomer;Morbidity - disease rate;mortality;mouse model;Mus;neonatal Fc receptor;Nephritis;nephrotoxicity;neutrophil;novel;Outer Mitochondrial Membrane;Pathway interactions;Patients;Permeability;Play;podocyte;preservation;prevent;Proteinuria;Proteolytic Processing;Research;response;Role;Serum;Severity of illness;Signal Transduction;Sorting;Structure;T-Lymphocyte;targeted treatment;Testing;trafficking;transcriptome sequencing;Up-Regulation;Work

PROJECT_TITLE: Neonatal Fc Receptor (FcRn) Trafficking of Immune Complexes to the Lysosome as a Driver of Glomerulonephritis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-P(03)]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging

PI_NAMEs: JACKSON, WILLIAM F. (contact)

PROJECT_TERMS: 3-Dimensional;Adipocytes;Adipose tissue;Applications Grants;Blood Vessels;Cells;cellular imaging;Cost efficiency;Cultured Cells;design;Development;Equipment;Expenditure;experimental study;fabrication;Health;Human Resources;Image;Image Analysis;Immune;in vivo;instrument;intravital microscopy;laboratory facility;live cell imaging;Methods;Michigan;Microscopy;Nerve;novel strategies;optical imaging;Preparation;Program Research Project Grants;Quality Control;real-time images;reconstruction;Reproducibility;Research Personnel;Science;Services;Slide;Techniques;Time;Tissue imaging;Tissues;Training;Universities

PROJECT_TITLE: Core D (Microscopy Core)


NIH_SPENDING_CATS: Bioengineering

PROJECT_TERMS: Adipocytes;adiponectin;Adipose tissue;Angiotensin II;Aortic coarctation;Arteries;Blood;Blood flow;blood pressure elevation;Blood Vessels;cell type;Cells;Chemicals;clinically relevant;Collagen;Communication;Communications Media;Contracts;Data;Diet;Disease;Disease Progression;Elastin;Elements;Environment;Excision;experimental study;Exposure to;Goals;Health;Heart;High Fat Diet;Homeostasis;Homing;Hypertension;Immune;Impairment;improved;Individual;Investigation;Knowledge;Maintenance;Measures;Mechanics;mechanotransduction;Modeling;Nature;nerve supply;Neurotransmitters;novel;Nutrient;peripheral blood vessel;Physiological;pressure;Property;Relaxation;response;Signal Transduction;Solid;Stress;Stretching;Testing;Thoracic aorta;Tissues;transcriptome sequencing;transmission process;Tunica Adventitia;wasting;Whole Blood;Work

PROJECT_TITLE: PVAT mechanics in health and disease


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Prevention;Social Determinants of Health

PI_NAMEs: TOSTESON, ANNA N. A. (contact)

PROJECT_TERMS: Achievement;Address;Affect;Age;anti-cancer research;Area;Automobile Driving;base;Cancer Biology;Cancer Burden;Cancer Center;Cancer Center Support Grant;Cancer Control;Cancer health equity;cancer site;Cancer Survivor;Catchment Area;Categories;Classification;Clinical Research;Clinical Trials;Code;Collaborations;Communities;community advisory board;community collaboration;community engaged intervention;community engagement;Community Outreach;community research;Comprehensive Cancer Center;County;Data;Death Rate;Disparity;Early Diagnosis;economic determinant;Education;Ensure;Ethnic Origin;Etiology;Event;Grant;Health behavior;health equity;Health Service Area;Health Services Accessibility;Health system;Incidence;Income;Individual;Infrastructure;Intervention;Knowledge;Malignant Neoplasms;Measures;metropolitan;Mission;Monitor;mortality;NCI Center for Cancer Research;NCI-Designated Cancer Center;New England;Norris Cotton Cancer Center;Observational Study;Play;Policies;Population;population migration;Prevalence;Prevention;programs;Publications;Race;Research;research study;Resources;Risk;Risk Factors;Role;Rural;rural area;Rural Community;Rural Population;screening;social determinants;Solid;survivorship;Translating;Translations;Underserved Population;Work

PROJECT_TITLE: Community Outreach and Engagement


ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative/Relevance: Sepsis is an overwhelming inflammatory response to infection and is the most common cause of kidney injury in intensive care units. Serum ferritin light chain (FtL) is elevated during sepsis but the contributory role thereof in inflammation is not known; therefore, our study is designed to evaluate the role of FtL in mitigating the sepsis- induced hyperinflammatory response and kidney injury. Success in this endeavor will justify development of FtL as a new treatment for this devastating condition.

PI_NAMEs: BOLISETTY, SUBHASHINI  (contact)

PROGRAM_OFFICER_NAME: SADUSKY, ANNA BURKART

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Biogenesis;carboxypeptidase C;Cathepsins;cecal ligation puncture;Cells;Clinical Research;clinically relevant;Creatinine;Critical Illness;Cystatins;cytokine;cytokine release syndrome;Data;design;Development;Disease;Disparate;Endotoxemia;Extracellular Signal Regulated Kinases;Ferritin;Functional disorder;gain of function;Gene Expression;Genes;Genetic;Glycolysis;Health Expenditures;Homeostasis;Hypoxia Inducible Factor;immunoregulation;In Vitro;in vivo Model;Infection;Inflammation;Inflammatory;Inflammatory Response;Infusion procedures;Inhibition of NF-KB activation;inhibitor;Injury;Injury to Kidney;Intensive Care Units;Interleukin-6;Iron;Kidney;kidney cell;Knowledge;LCN2 gene;Left;Light;Lipopolysaccharides;loss of function;Macrophage;Mediating;Mediator;Metabolism;Mitochondria;mitochondrial dysfunction;Modeling;Morbidity - disease rate;mortality;mortality risk;mouse model;Mus;Myelogenous;Myeloid Cells;neutrophil;NF-kappa B;novel;overexpression;Oxidative Stress;Pathogenesis;Pathogenicity;Patients;peroxisome;Phenotype;Physiological;Population;PPAR gamma;preclinical study;preservation;prevent;Production;Proteins;Proximal Kidney Tubules;rat KIM-1 protein;Recombinants;Renal function;Reporting;response;Role;Saline;Sepsis;Serum;Signal Transduction;single-cell RNA sequencing;Site;success;Testing;Therapeutic;therapeutic target;therapeutically effective;TNF gene;tool;transcriptome;transcriptome sequencing;Transgenic Mice;Tubular formation;Up-Regulation;Wild Type Mouse;Work

PROJECT_TITLE: Functional Significance of Ferritin Light Chain in Sepsis-associated Kidney Injury

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


PI_NAMEs: GULBRANSEN, BRIAN D. (contact)

PROJECT_TERMS: Adipocytes;Adipose tissue;Adult;American;analog;Anatomy;Animal Model;Animals;Aorta;Atherosclerosis;Autocrine Communication;Biological Assay;Blood Pressure;blood pressure regulation;Blood Vessels;burden of illness;Calcium;calcium indicator;Cannulations;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;Cardiovascular system;Catecholamines;Cause of Death;Cells;Complication;Cues;Data;Disease;early onset;Epidemic;experimental study;Female;Genes;Genetic;Goals;Health;Health Care Costs;Heart failure;High Fat Diet;Human;Hypertension;Image;Impairment;improved;In Vitro;Individual;insight;Label;male;Measures;Mediating;Mediator;Mesenteric Arteries;Mesentery;Minor;Modeling;Morbidity - disease rate;Mus;Nerve;nerve supply;neural;Neuroglia;neuroregulation;neurotransmission;neurotransmitter release;neurotransmitter uptake;Neurotransmitters;Norepinephrine;novel;novel therapeutics;Obesity;Optics;Pathway interactions;Pharmaceutical Preparations;Play;Preparation;presynaptic;preventable death;Production;Regulation;Reporter;Reporter Genes;response;Role;Signal Transduction;single-cell RNA sequencing;Source;Stroke;synaptic function;Testing;Tetrodotoxin;therapy development;Thoracic aorta;Tissues;transcriptome sequencing;Transgenic Animals;Transgenic Model;Transgenic Organisms;uptake;Vascular Diseases;Vasodilation

PROJECT_TITLE: Neurohumoral regulation of PVAT


NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Biotechnology;Brain Disorders;Genetics;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_DEPT: GENETICS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Amyotrophic lateral sclerosis (ALS) involves the loss of axons, including the essential connections between spinal cord neurons and muscles. The SARM1 enzyme is the central regulator of axon maintenance that triggers neurons to actively dismantle their axons. We have shown that mutated versions of the SARM1 gene found in some ALS patients can kill neurons and paralyze mice. Here we investigate the role of the SARM1 axon degeneration pathway in ALS in search of a therapy.

PI_NAMEs: BLOOM, ADAM JOSEPH (contact);DIANTONIO, AARON ;MILBRANDT, JEFFREY D

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Affect;Alleles;ALS pathology;ALS patients;Amino Acids;Amyotrophic Lateral Sclerosis;Attenuated;Axon;axon injury;axonal degeneration;Biological Assay;Categories;Cell Death;Cessation of life;Chemicals;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Complex;Data;Development;Disease;disease model;Disinhibition;disorder risk;Dominant-Negative Mutation;druggable target;enzyme activity;Enzymes;Etiology;experimental study;Face;falls;Foundations;Functional disorder;gain of function;gain of function mutation;gene therapy;General Population;Genes;Genetic Polymorphism;genetic risk factor;Genetic study;genetic variant;Genetic Variation;genome wide association study;genotyped patients;Human;Human Genetics;human induced pluripotent stem cells;inhibitor therapy;Injury;innovation;Investigation;Knock-in;Knock-in Mouse;Knockout Mice;life span;Link;loss of function;Maintenance;Mediating;member;Messenger RNA;Metabolic;Methods;Modeling;Molecular;Motor;motor disorder;Motor Neurons;mouse model;Mus;Muscle;Mutate;Mutation;NAD+ Nucleosidase;Nerve Degeneration;Nervous System;neurodegenerative phenotype;neuron loss;Neuronal Differentiation;Neurons;Neuropathy;neuroprotection;novel;overexpression;Paralysed;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Phenotype;Process;programs;protein TDP-43;Protein Truncation;Proteins;Risk;Role;Route;small molecule inhibitor;Spinal Cord;Structure;superoxide dismutase 1;Symptoms;TDP-43 aggregation;Testing;Therapeutic;Trauma;Variant;Viral

PROJECT_TITLE: SARM1 functional polymorphisms and their contribution to ALS risk

STUDY_SECTION: CMND

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


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Influenza;Lung;Pneumonia;Pneumonia and Influenza

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: The synergy between Streptococcus pneumoniae and influenza during co-infection has long been recognized and our data indicate that this synergy is operative on a physical level, as influenza A virus (IAV) binds to the surface of S. pneumoniae, providing fitness benefits to both pathogens. This proposal will determine the bacterial and viral factors that promote this interaction and the role of these interactions on host-pathogen interactions.

PI_NAMEs: ROSCH, JASON W. (contact);SCHULTZ-CHERRY, STACEY L;VAN OPIJNEN, TIM

PROGRAM_OFFICER_NAME: UPADHYAY, MEENU MISHRA

PROJECT_TERMS: Adherence;Area;Bacteria;Bacterial Adhesion;bacterial genetics;Bacterial Pneumonia;Bacteriophages;Binding;Characteristics;co-infection;Complex;Coupled;cross immunity;Data;Desiccation;Disease;Epithelial Cells;experimental study;fitness;Flow Cytometry;Future;Genes;Genus staphylococcus;glycosylation;Goals;Hemagglutinin;Hemophilus;Human;human disease;Immune response;In Vitro;in vivo;Infection;Influenza;Influenza A virus;insight;Intervention;Investigation;Mediating;Modeling;Moraxella;Mus;mutant;Neuraminidase;novel;pathogen;Polysaccharides;Population;Predisposition;Proteins;respiratory;respiratory pathogen;Respiratory System;Respiratory Tract Infections;respiratory virus;Role;Secondary to;Streptococcus pneumoniae;Surface;synergism;therapeutic development;tissue tropism;transcriptome sequencing;transmission process;transposon sequencing;Viral;Viral Hemagglutinins;viral transmission;Virulence;Virus;Virus Diseases

PROJECT_TITLE: Consequences of Direct Viral-Bacterial Interactions

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


NIH_SPENDING_CATS: Biotechnology;Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research

PI_NAMEs: LEACH, STEVEN D (contact)

PROJECT_TERMS: Award;Biometry;Cancer Center Support Grant;cancer research center director;Cells;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;college;Coupled;Development;Direct Costs;Emerging Technologies;Engineering;Evaluation;Faculty;Faculty Recruitment;Funding;Funding Mechanisms;Gene Transfer;Genomics;Health;Immunooncology;Individual;Infrastructure;innovation;Investments;Malignant Neoplasms;member;Molecular Biology;mouse model;NCI Center for Cancer Research;Needs Assessment;Norris Cotton Cancer Center;novel;Pathology;patient derived xenograft model;Peer Review;Philanthropic Fund;Pilot Projects;Population Research;precision oncology;preference;Prevention;Process;programs;Publications;Radar;Recording of previous events;recruit;Registries;Reporting;Research;Research Personnel;Resource Sharing;Resources;Rural Population;Science;Secure;Service provision;Services;Strategic Planning;survivorship;System;Techniques;Translational Research;Work

PROJECT_TITLE: Developmental Funds


PI_NAMEs: ROCKWELL, CHERYL ELIZABETH (contact)

PROJECT_TERMS: Adipose tissue;Adoptive Transfer;Adult;Animals;Automobile Driving;Blood Pressure;Blood Vessels;Buffers;CD8-Positive T-Lymphocytes;Cell Physiology;Cell Separation;Cells;Cessation of life;cytokine;Data;Development;dietary control;Disease;Environment;Etiology;Future;Granulocyte-Macrophage Colony-Stimulating Factor;Health;Heart Diseases;High Fat Diet;High Prevalence;Homeostasis;Hypertension;hypertensive;Immune;immune function;Immune system;Immunity;immunoregulation;Inbred Dahl Rats;Individual;Inflammation;Inflammatory;inflammatory milieu;inhibitor;insight;Interferon Type II;Interleukin-2;knock-down;Knowledge;Ligands;Link;Mesentery;Modeling;novel;Obesity;Patients;Peptide Hydrolases;Population;PPAR gamma;Prevalence;Production;Public Health;Rattus;Refractory;Risk;RNA Interference;Role;T-Cell Activation;T-Cell Depletion;T-Lymphocyte;Testing;Therapeutic;Time;Tissues;transcriptome sequencing;White Blood Cell Count procedure

PROJECT_TITLE: Regulation of immune cell function by the PVAT microenvironment


NIH_SPENDING_CATS: Cancer

PROJECT_TERMS: Achievement;Applications Grants;Area;Award;Cancer Center Support Grant;Capital;career;clinical implementation;Collaborations;Communities;community engagement;Community Outreach;Development;Engineering;Environment;Evaluation;expectation;experience;Faculty Recruitment;Formulation;Funding;Future;Goals;Immunology;Individual;insight;Institution;Intellectual Property;Investments;Leadership;member;multidisciplinary;NCI Center for Cancer Research;Norris Cotton Cancer Center;Parents;peer;Peer Review;Population Sciences;Positioning Attribute;Process;programs;Qualifying;Recommendation;Research;Research Infrastructure;Resource Sharing;Role;Science;Secure;Services;Strategic Planning;Strategic vision;Training;Translations;Vision;Work

PROJECT_TITLE: Leadership, Planning and Evaluation


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Neurosciences;Social Determinants of Health

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: The Summer Physiology Undergraduate Researcher (SPUR) Program addresses biomedical science research and education disparities found in undergraduate students from underrepresented minorities (URMs) by providing them with mentored research experience and training. We will support the SPUR students through hands-on research training in the laboratories of SPUR Program faculty, classroom lectures on fundamentals of neuroscience and training in responsible conduct of research during a 10-week summer Program. Through mentoring and training, we seek to build a pipeline for SPUR undergraduates, including URMs, to pursue research careers in biomedical sciences.

PI_NAMEs: BHAT, MANZOOR A. (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Address;Advertising;Advisory Committees;Advocate;Area;Asian;Awareness;Bachelor's Degree;Biology;Biomedical Research;Black race;Brain;career;career preparation;Clinical Research;Collaborations;Communication;Communities;Competence;Complement;Data;Department chair;design;Development;disabled students;Disparity;Doctor of Medicine;Doctor of Philosophy;Education;Education Projects;Educational workshop;Ensure;Environment;Ethnic Origin;experience;Faculty;faculty mentor;Feedback;Generations;Goals;hands on research;Health;Hispanic;Hispanic-serving Institution;Hour;implicit bias;improved;innovation;Institution;interest;Interview;Laboratories;Laboratory Research;Learning;lectures;Low income;Mentors;Minority;Minority Participation;minority undergraduate;Minority-Serving Institution;Mission;National Institute of Neurological Disorders and Stroke;Native Americans;Nervous System;Nervous System Disorder;Neurosciences;peer;Physiology;Population;Principal Investigator;programs;Quality of life;recruit;Recruitment Activity;Reporting;Research;Research Personnel;Research Technics;Research Training;responsible research conduct;Running;satisfaction;Science;Scientist;Self Efficacy;skills;socioeconomic diversity;socioeconomics;stem;Students;success;summer program;symposium;Techniques;Texas;Training;Training Programs;undergraduate student;Underrepresented Minority;underrepresented minority student;Universities;Work;Writing


ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: Narrative Up to 30% of patients surviving subarachnoid hemorrhage develop delayed functional deficits 4-10 days post- SAH which is a major clinical concern. Microthrombi, infarction, and inflammation may be contributing factors and this proposal is designed to investigate which of these factors are crucial for delayed deficits. This research will also determine if microthrombi and/or inflammation are causes of delayed deficits and identify potential therapeutic targets delayed functional deficits after subarachnoid hemorrhage.

PI_NAMEs: MCBRIDE, DEVIN WILLIAM (contact)

PROGRAM_OFFICER_NAME: KOENIG, JAMES I

PROJECT_TERMS: Amidines;Aneurysmal Subarachnoid Hemorrhages;Antibodies;Antiplatelet Drugs;Attenuated;Autopsy;Behavioral;Blood Platelets;Brain;brain tissue;Cell Death;Cells;Cerebral Ischemia;cerebral microvasculature;Cerebrum;Chromatin;Clinical;Clinical Research;Clinical Trials;cytokine;Data;Deoxyribonuclease I;Deposition;design;Development;Etiology;experimental study;extracellular;Flow Cytometry;functional outcomes;Goals;histological stains;Human;Image;imaging modality;Immune;immune cell infiltrate;improved;Incidence;Infarction;Inflammation;Inflammatory Response;Injury;innovation;Internet;intravital microscopy;Ischemia;Laser Speckle Imaging;Link;longitudinal analysis;Magnetic Resonance Imaging;Mediating;Memory;Morbidity - disease rate;mortality;mouse model;Mus;neurobehavior;Neurologic;Neurologic Deficit;neutrophil;Outcome;Patient-Focused Outcomes;Patients;Perforation;Performance;Perfusion;Peripheral;Platelet Activation;Platelet aggregation;Platelet Inhibitors;Play;pre-clinical research;prevent;prototype;Reporting;Research;Role;scaffold;Subarachnoid Hemorrhage;Testing;therapeutic target;Thrombosis;Thrombus;Vasospasm

PROJECT_TITLE: Role of Microthrombi and Inflammation in Delayed Deficits after SAH

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


NIH_SPENDING_CATS: Cancer;Patient Safety

PI_NAMEs: DRAGNEV, KONSTANTIN H. (contact)

PROJECT_TERMS: Address;Adult;Adverse event;Amendment;American College of Radiology Imaging Network;anti-cancer research;authority;Cancer Center;Cancer Center Support Grant;Cancer Patient;Catchment Area;Charge;Childhood;Clinical;Clinical Cancer Center;Clinical Data;Clinical Management;Clinical Protocols;Clinical Research;clinical trial participant;Clinical Trials;Clinical Trials Data Monitoring Committees;Data;data integrity;data management;Early Therapeutic-Clinical Trials Network;Eastern Cooperative Oncology Group;Enrollment;experience;Failure;Female;Goals;Health system;improved;Industry;Institution;Institutional Review Boards;Intervention Trial;investigator-initiated trial;Lead;Malignant Neoplasms;member;Monitor;Monitoring Clinical Trials;multidisciplinary;NCI Center for Cancer Research;Norris Cotton Cancer Center;Nursing Research;Office Management;Parents;Participant;participant safety;Patients;Pharmacy facility;Phase;Population;programs;protocol development;Protocols documentation;Qualifying;Reapplication;Recommendation;Reporting;Research;Research Personnel;research study;Resources;Review Committee;Risk;Safety;screening;Serious Adverse Event;Services;Site;Study Subject;Woman

PROJECT_TITLE: Clinical Protocol and Data Management (CPDM)


NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Hypertension;Obesity;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PI_NAMEs: CONTRERAS, GENARO ANDRES (contact)

PROJECT_TERMS: adipocyte biology;Adipocytes;adipokines;Adipose tissue;Adult;Affect;Anatomy;Animal Experiments;Animals;Blood Pressure;blood pressure control;Blood Vessels;Cardiovascular Diseases;cell growth;Cells;Cessation of life;Cues;Data;Development;dietary control;experimental study;Exposure to;Extracellular Matrix;Extracellular Structure;Fatty acid glycerol esters;Female;fibroblast growth factor 9;Fibroblasts;Fibrosis;Functional disorder;Health;High Fat Diet;Hypertension;hypertension control;Hypertrophy;Immune;in vitro Model;Incidence;Intervention;Knowledge;lipid biosynthesis;male;mechanical force;mechanical signal;Mechanics;migration;Modeling;Modification;Mus;normotensive;novel;Obesity;Overweight;Pathogenesis;Pathologic;Patients;Pattern;Pericytes;Phenotype;physical property;Piezo 1 ion channel;Platelet-Derived Growth Factor alpha Receptor;Population;pressure;Prevalence;Process;progenitor;Rattus;Resistance;response;Role;Shapes;Signal Transduction;Source;stem cell biology;stem cells;Structure;synergism;Testing;Tissues;Tunica Adventitia;Tunica Intima;Tunica Media;Variant;Vascular remodeling

PROJECT_TITLE: The perivascular adipocyte: integrating mechanical and structural cues into vasoactive function


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: STANFORD

ORG_DEPT: BIOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: Dendrites are highly branched neuronal processes that serve as the “antenna” of neurons to gather information. Understanding the molecular mechanisms underlying dendrite growth and branching will provide the basis for developing new strategies for combating developmental neurological diseases and for slowing down the progression of neurodegenerative diseases. In addition, such knowledge will be helpful for developing strategies to promote the regeneration of neural circuits after stroke.

PI_NAMEs: SHEN, KANG  (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Actins;Address;Affect;Animals;Area;Axon;Binding;Binding Proteins;Biochemical;Biological Assay;Biological Models;Caenorhabditis elegans;Cell model;Cell Physiology;Cells;Cis Tests;Complex;Control Animal;Cytoplasmic Tail;Cytoskeleton;Dendrites;Detection;Development;Drug Targeting;Event;experimental study;extracellular;F-Actin;Family;Feedback;Funding;genetic analysis;Grant;Growth;in vivo;information gathering;insight;Integral Membrane Protein;Ion Channel;Knowledge;Ligand Binding;Ligands;Literature;Locomotion;Logic;Lysosomes;Mediating;Modeling;Modification;Molecular;Morphogenesis;Motor;Movement;Muscle;Muscle Cells;Muscle Contraction;mutant;Mutation;Mutation Analysis;Nerve Regeneration;nerve supply;Nervous System Disorder;Neural Cell Adhesion Molecule L1;neural circuit;Neurodegenerative Disorders;neuromuscular activity;Neuromuscular Junction;Neurons;Neuropeptides;novel;Pathway interactions;Pattern;Peptide Hydrolases;polymerization;Polymers;post stroke;Process;Proprioceptor;Proprotein Convertases;Proteins;receptor;Receptor Signaling;recruit;Regulation;Research;Sensory;Signal Transduction;Site;Skin;Surface;System;Testing;Tight Junctions;Work

PROJECT_TITLE: Patterning dendritic branches with environmental and neuronal surface molecules

STUDY_SECTION: SYN

STUDY_SECTION_NAME: Synapses, Cytoskeleton and Trafficking Study Section[SYN]


NIH_SPENDING_CATS: Cancer;Patient Safety;Prevention

PI_NAMEs: LEWIS, LIONEL DAVID (contact)

PROJECT_TERMS: Advocacy;Amendment;authority;Basic Science;behavioral study;Biomedical Engineering;Biometry;Cancer Center;Cancer Center Support Grant;cancer prevention;Charge;Clinical;Clinical Oncology;Clinical Pharmacology;Clinical Research;Clinical Trials;Collection;college;Committee Members;Communication;Data;Discipline;Enrollment;falls;Funding Agency;Hematology;human subject;human subject protection;Immunology;Institutional Review Boards;Intervention;Intervention Trial;Light;Logistics;Malignant Neoplasms;Medical Oncology;member;Modification;Monitor;multidisciplinary;NCI Center for Cancer Research;Norris Cotton Cancer Center;Oncology;Oncology Group;Participant;participant safety;Pathology;Patient Outcomes Assessments;patient population;Pediatric Oncology;Peer Review;Population;Population Sciences;Principal Investigator;Process;programs;Protocols documentation;Published Comment;Quality of life;Radiation Oncology;Recommendation;Regulation;Research;Research Activity;research study;Review Committee;Safety;safety outcomes;screening;Suggestion;Surgical Oncology;survivorship;System;Time;United States National Institutes of Health

PROJECT_TITLE: Protocol Review and Monitoring System (PRMS)


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_DEPT: BIOMEDICAL ENGINEERING

PHR: PROJECT NARRATIVE  It has long been known that the brains of people with Alzhimer's disease are less stiff than those of healthy individuals, yet it has only recently been appreciated that these biomechanical changes occur years or decades before clinical symptoms arise, suggesting that they may be involved in the development of Alzheimer's disease. To help study and inform future therapies targeting this pathway, we have developed a novel three-dimensional (3D) decellularized brain extracellular matrix (dBECM) gels that have tunable mechanical properties, and we have combined them with 3D stem cell-based models of human brain tissue, known as cerebral organoids (COs). Here, we propose to systematically vary the stiffness of dBECM gels, and to evaluate the resulting effects on the development of Alzheimer's disease neuropathology (amyloid and tau neurofibrillary tangles), neurodegeneration, astrogliosis, and mechanical property alterations of embedded CO models of Alzheimer's disease.

PI_NAMEs: JOHNSON, NOAH RAY;PARK, DAE WON  (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: 3-Dimensional;abeta accumulation;Address;Aducanumab;age related changes;aging brain;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease therapeutic;Alzheimer’s disease biomarker;American;Amyloid;Amyloid beta-Protein;astrogliosis;Attention;Back;Biochemical;Biological Markers;Biomechanics;Brain;brain tissue;Caregivers;Cause of Death;Cell Line;Cerebrum;Clinical;cognitive change;Data;Dementia;Development;Disease;disease phenotype;Disease Progression;Environment;experimental study;extracellular;Extracellular Matrix;Family;Formulation;Functional disorder;Future;Gel;Healthcare Systems;Hippocampus;Human;human disease;human induced pluripotent stem cells;human model;Immunotherapy;Impaired cognition;Impairment;in vivo;in vivo Model;Individual;Investigation;Link;Magnetic Resonance Elastography;mechanical properties;Mechanics;Medical;Modeling;Molecular;Neocortex;Nerve Degeneration;Neurodegenerative Disorders;neurofibrillary tangle formation;Neurofibrillary Tangles;neurogenesis;neuron loss;Neurons;neuropathology;Normal Range;novel;Organoids;Pathogenesis;Pathologic;Pathway interactions;Patients;Persons;photolysis;Polyethylene Glycols;Process;progressive neurodegeneration;Property;Proteins;Proteomics;Research;Role;Senile Plaques;stem cell model;Structure;Symptoms;targeted treatment;tau aggregation;tau-1;Testing;Therapeutic;therapeutic target;therapeutically effective;three-dimensional modeling;Tissues;tool;viscoelasticity

PROJECT_TITLE: Determining the role of tissue stiffness in the development of Alzheimer's disease pathology

STUDY_SECTION: BNVT

STUDY_SECTION_NAME: Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section[BNVT]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: NEW YORK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE Both humans and birds depend primarily on vision to navigate their environment and to remember where things are. This project uses an innovative experimental and computational approach in birds with remarkable memory abilities to dissect how memory circuits process visual information. The results will have broad scientific relevance by revealing fundamental properties of memory circuits across vertebrates, and will support the ability of future technology to improve memory function in health and disease.

PI_NAMEs: PAYNE, HANNAH L (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Address;Alzheimer's Disease;analog;Anatomy;Animals;Apical;Architecture;Area;Back;Behavior;Behavioral;bird song;Birds;Brain;career;career development;Cells;Code;complex data;Data;Data Set;design;Development Plans;Disease;Dissociation;Engineering;Ensure;Environment;Event;Evolution;Exhibits;experience;Exposure to;extrastriate visual cortex;Eye Movements;Feedback;Food;Future;gaze;Goals;Head;Health;Hippocampus;Human;imprint;improved;innovation;insight;Learning;Location;Mammals;member;Memory;memory process;memory retrieval;Mentors;model organism;Modeling;neural;Neural Network Simulation;Neural Pathways;Neurons;Neurosciences;novel;optogenetics;Organism;Pathway interactions;Pattern;Perception;Phase;Positioning Attribute;Primates;Process;Property;Publishing;Recording of previous events;Research;Research Personnel;Research Project Grants;Retina;Retrieval;Rodent;Role;Saccades;sensory input;Silicon;Site;spatial memory;Specialist;Structure;System;Techniques;Technology;Testing;Thalamic structure;Time;Toy;Training;Universities;Vertebrates;Vision;Visual;Visual Cortex;visual information;visual processing;Visuospatial;Washington;Work

PROJECT_TITLE: Processing of visual information by spatial memory circuits in the avian brain


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Brain Disorders;Chronic Fatigue Syndrome (ME/CFS);Chronic Pain;Coronaviruses;Emerging Infectious Diseases;Infectious Diseases;Neurosciences;Pain Research;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: NARRATIVE We will use drop-of-blood microfluidic assays to measure key neutrophil functions, and multiplexed cytokine arrays to assess the underlying plasma milieu in ME/CFS, PASC, and healthy control subjects. We will also correlate neutrophil function with cytokine profiles and stratify according to time-since-illness-onset to identify potential indicators of disease progression.

PI_NAMEs: ELLETT, FELIX  (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Behavior;Biological Assay;Blood;Cells;Chronic Fatigue Syndrome;Circulation;cohort;complex chronic conditions;COVID-19;COVID-19 sequelae;cytokine;Diagnosis;Disease Progression;Drops;Encephalitis;Etiology;Exhibits;extracellular;Fingers;Future;Goals;Immune;In Vitro;Inflammatory;Long COVID;Longitudinal Studies;Measures;Microfluidics;Motility;Myalgia;neutrophil;Onset of illness;Outcome;Plasma;Post-Acute Sequelae of SARS-CoV-2 Infection;response;Sampling;SARS-CoV-2 infection;Signal Transduction;Time

PROJECT_TITLE: Correlating neutrophil function and plasma cytokine profiles with progression of ME/CFS and Long-Covid/PASC

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CFS-N(80)S]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: VALHALLA

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: NEW YORK MEDICAL COLLEGE

PHR: PROJECT NARRATIVE Group A streptococci cause a diverse array of >750 million infections each year throughout the world. These infections lead to >500,000 deaths and trigger autoimmune disorders as well. Due to the high rates of morbidity and mortality, development of a safe and effective vaccine is a priority.

PI_NAMEs: BESSEN, DEBRA E (contact)

PROGRAM_OFFICER_NAME: GU, XIN-XING

PROJECT_TERMS: Abbreviations;Accounting;Active immunity;Adult;Age;Animal Model;Animals;Antibodies;Antibody-mediated protection;Antigen Targeting;Antigens;Autoimmune Diseases;Bacteria;Binding;Biological;Carbohydrates;Cessation of life;Child;Childhood;Clinical Trials;Collection;Colony-forming units;comparison group;Complex;Data;Development;Disease;disease model;Dose;Elements;Epidemiological trend;Epithelium;Equation;Exhibits;Failure;Fibronectins;flexibility;Future;General Practitioners;Goals;Habitats;Human;human disease;human subject;human tissue;humanized mouse;Immune response;Immunity;Immunize;immunodeficiency;Immunodeficient Mouse;immunodeficient mouse model;Immunoglobulins;immunoreactivity;Impetigo;improved;Incidence;Infection;Infectious Skin Diseases;Lead;Life;longitudinal, prospective study;Lymphoid Tissue;Measures;Modeling;Morbidity - disease rate;mortality;mouse model;multiple myeloma M Protein;Mus;Nose;novel;Organ;Passive Immunity;Passive Immunization;pathogen;Pharyngeal structure;Physiological;Plasminogen;preclinical development;Predisposition;protective efficacy;relative effectiveness;Resources;Rest;Route;screening;Secretory Immunoglobulin A;Serology;Serum;Severe Combined Immunodeficiency;Skin;Soft Tissue Infections;Source;Specialist;Specificity;Specimen;Standardization;Streptococcal Infections;Streptococcal Vaccines;Streptococcus;Streptococcus pyogenes;Streptolysins;Surface;Swab;Testing;transmission process;Upper Respiratory Infections;Upper respiratory tract;vaccine candidate;vaccine development;Vaccines;Virulence;Virulence Factors;Work;wound

PROJECT_TITLE: Protective antibody in streptococcal infection models


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetics;Microbiome;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: PATHOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative A mutation in C9ORF72, a gene of poorly defined function, is the most common cause of Frontotemporal dementia and Amyotrophic lateral sclerosis, neurodegenerative disorders that together affect approximately sixty thousand individuals in the United States and approximately 1.4 million people worldwide. This proposal seeks to identify bacteria within the gut that contribute to neural inflammation in mice with a C9ORF72 mutation. New germ-free mouse models generated may be useful to reveal pathways important for neurodegeneration and in the future could serve as screening platforms for candidate dementia therapeutics.

PI_NAMEs: BURBERRY, AARON  (contact)

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: Adult;Affect;Amyotrophic Lateral Sclerosis;Animals;Bacteria;Behavior;Biological Assay;Brain;brain tissue;C9ORF72;cell type;Cells;Central Nervous System;chemokine;Chromosome 9;Clinical;Cognition;cytokine;Data Set;Dementia;Diagnosis;Dipeptides;Disease;disorder risk;Environment;Environmental Risk Factor;Enzyme-Linked Immunosorbent Assay;Etiology;experience;experimental study;Exposure to;Failure;Family;fecal transplantation;Feces;Flow Cytometry;follow-up;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Future;gene product;Genes;Genetic;Genetic Transcription;Genotype;Germ-Free;glial activation;gut bacteria;gut microbiome;Health;Heterogeneity;High Prevalence;Human;Immune;Immune system;Individual;Infiltration;Inflammatory;inflammatory milieu;Inflammatory Response;Inherited;insight;interest;Intervention;Language;Lobe;loss of function;loss of function mutation;Macrophage;Mass Spectrum Analysis;Memory impairment;metabolomics;Microbe;microbial community;Motor Neuron Disease;mouse model;multiplex assay;Mus;mutant;Mutant Strains Mice;Mutation;Nerve Degeneration;Nervous System;neural;Neurodegenerative Disorders;neuroinflammation;neuron loss;neutrophil;Open Reading Frames;Organism;Outcome;Pathway interactions;Patients;Penetrance;Peripheral;personalized medicine;Persons;Phenotype;Plasma;Pre-Clinical Model;premature;Production;Proteins;Proxy;Publishing;Research;response;RNA;screening;Semantics;Syndrome;T cell infiltration;targeted treatment;Therapeutic;TNF gene;trafficking;Translations;Transplantation;United States

PROJECT_TITLE: Bacterial triggers of neural inflammation.

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ORG_CITY: SAN DIEGO

ORG_NAME: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO

PHR: PROJECT NARRATIVE The proposed work will use a transdisciplinary approach to dissect how a hormone that is produced in our body and widely implicated in the development of metabolic diseases (hypertension and diabetes) is also critical for the regulation of gut physiology including age-associated gut dysmotility. These studies are likely to shed light into what molecular mechanisms are involved in gut dysmotility in older people, which potentiates infections, causes nutrient malabsorption, and manifests with debilitating symptoms, such as gastroparesis, intestinal pseudo-obstruction, diarrhea, constipation, Hirschprung’s disease, and fecal incontinence. This information is crucial so that scientists can begin to understand how hormones released in the gut can regulate gut motility and develop targeted therapeutics to modulate such motility in a variety of gut diseases associated with aging and gut dysmotility.

PI_NAMEs: MAHATA, SUSHIL K (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: Acetylcholine;Affect;age related;Aging;Agonist;antagonist;Autopsy;Brain;Catecholamines;Cells;Central Nervous System;cholinergic;Cholinergic Receptors;Chromogranin A;Chronic;Clinical Chemistry;combat;Constipation;Cost of Illness;debilitating symptom;Development;Diabetes Mellitus;Diarrhea;Disease;Dopamine;Enteral;Enteric Nervous System;Enterochromaffin Cells;experience;experimental study;Failure;Fecal Incontinence;Frequencies;Ganglia;Gastric Emptying;Gastrointestinal Diseases;Gastroparesis;Half-Life;Health;Hematology;Histologic;Hormones;Human;Hypertension;improved;Incidence;Infection;Innate Immune System;Interneurons;Interstitial Cell of Cajal;Intestinal permeability;Intestinal Pseudo-Obstruction;Intramuscular;Knock-out;Knockout Mice;Light;Link;Liquid substance;Maintenance;Malabsorption Syndromes;Measures;Mediating;Metabolic Diseases;microbiome composition;mimetics;Molecular;Motility;motility disorder;Motor Neurons;Mucous Membrane;Mus;Muscle;Muscle Cells;Myenteric Plexus;neural;Neurites;Neuroglia;neuronal cell body;Neurons;Neurotransmitters;novel therapeutics;Nutrient;nutrient absorption;Obese Mice;old mice;older adult;Older Population;Organ;Outcome;Pacemakers;Pathway interactions;Peptides;pharmacophore;Phenotype;Physiology;Plasma;Population;prevent;Prevention;Process;Production;Quality of life;receptor;Receptor Signaling;Regulation;Resistance;Risk;Scientist;Serotonin;Serotonin Receptors 5-HT4;small molecule;Smooth Muscle Myocytes;Solid;Stimulus;Stomach;Submucosa;Submucous Plexus;Substance P;Supplementation;targeted treatment;Testing;Therapeutic;therapeutic target;Tissues;Toxic effect;Translating;transmission process;tumor growth;Visual;Work

PROJECT_TITLE: Peptide therapy for age-associated gut dysmotility

STUDY_SECTION: DNPD

STUDY_SECTION_NAME: Digestive and Nutrient Physiology and Diseases Study Section [DNPD]


NIH_SPENDING_CATS: Biotechnology;Cancer;Lung;Lung Cancer

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE The treatment of non-small cell lung carcinoma (NSCLC) with pemetrexed-based chemotherapy often leads to the development of resistance and therapeutic failure but the mechanism responsible for the resistance remains largely unclear. Through a customized RNAi screening, we identified FGFR3 signaling as a critical factor of pemetrexed resistance perhaps by mediating activation of a pemetrexed target enzyme in the folate metabolism and MAPK pathway. In this proposal, we will newly uncover the mechanism by which FGFR3 activates folate metabolism and MAPK pathway to drive pemetrexed resistance and validate the therapeutic efficacy of targeting FGFR3 signaling and pemetrexed as a novel combinatorial therapy for pemetrexed-resistant NSCLC.

PI_NAMEs: KANG, SUMIN  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Antibodies;Attenuated;Biological Assay;cancer cell;Cancer cell line;cancer therapy;cancer type;Cell Line;Cell Proliferation;Cell surface;Cell Survival;Chemoresistance;chemotherapy;Chemotherapy-Oncologic Procedure;Clinical;clinical application;clinical efficacy;combinatorial;Coupled;Data;Dihydrofolate Reductase;DNA biosynthesis;Dose;Down-Regulation;Enzymes;Failure;FGFR1 gene;FGFR3 gene;Fibroblast Growth Factor Receptors;Folic Acid;Folic Acid Antagonists;folic acid metabolism;Human;improved;In Vitro;in vivo;inhibitor;insight;interest;kinase inhibitor;Libraries;Link;Lung Adenocarcinoma;Malignant Epithelial Cell;Malignant neoplasm of lung;Malignant Neoplasms;MAP Kinase Gene;Mediating;Metabolic;Modeling;Molecular;mouse model;Mus;Non-Small-Cell Lung Carcinoma;novel;Oncogenic;Pathway interactions;patient derived xenograft model;Patients;Pemetrexed;pharmacologic;Phosphotransferases;Protein Isoforms;Protein Kinase;Protein-Serine-Threonine Kinases;Proteome;Regulation;Relapse;Research;Resistance;Resistance development;response;Ribosomal Protein S6 Kinase;Ribosomes;RNA interference screen;Role;Scaffolding Protein;screening;Series;Serine;Signal Pathway;Signal Transduction;small hairpin RNA;Therapeutic;therapeutic target;therapy outcome;Treatment Efficacy;Treatment outcome;tumor;tumor growth;tumor progression;Variant;Xenograft procedure

PROJECT_TITLE: Dissecting pemetrexed resistance in non-small cell lung carcinoma


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

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

PHR: Project Narrative Traditional Medicare covers fewer services than Medicaid with substantially higher cost-sharing. Low-income Medicare beneficiaries must navigate a complex set of programs for financial assistance with Medicare costs that have eligibility criteria that are not aligned with Medicaid expansion. This study will investigate whether the transition for Medicaid expansion enrollees to Medicare at age 65 results in racial and ethnic disparities in the comprehensiveness of coverage and contributes to disparities in service use, clinical event outcomes, and spending.

PI_NAMEs: FUNG, VICKI  (contact)

PROGRAM_OFFICER_NAME: SOLIS SANABRIA, CAROLINA VANESSA

PROJECT_TERMS: access disparities;Adopted;Adult;adverse outcome;Age;aged;Attention;Awareness;barrier to care;beneficiary;Black race;Caring;Clinical;Color;Complex;Control Groups;cost;Cost Sharing;COVID-19 pandemic effects;Data;Diagnosis;Disadvantaged;Disadvantaged minority;Disparity;Disparity population;Drug Prescriptions;Economics;Eligibility Determination;Emergency department visit;Enrollment;ethnic disparity;ethnic minority;Ethnic Origin;Event;Face;federal poverty level;Financial Support;Health;health care availability;health care disparity;health care service;Health Services;Health system;Healthcare Systems;Hispanic;Hospitalization;Household;human old age (65+);Income;Individual;Inpatients;Insurance;Insurance Coverage;life span;Link;Low income;low socioeconomic status;Machine Learning;Managed Care;Measures;Medicaid;Medicaid eligibility;Medicaid services;Medical Care Costs;Medicare;Medicare Part A;Medicare/Medicaid;Minority;mortality;Outcome;outcome disparities;Outpatients;Pharmaceutical Preparations;Policies;poor communities;Population;programs;Qualifying;Quality of Care;Race;racial disparity;racial minority;Research;Services;social culture;socioeconomics;Surveys;Testing;Time;Uninsured Medical Expense;Visit

PROJECT_TITLE: The Transition from Medicaid to Medicare and Impacts on Disparities in Coverage and Care

STUDY_SECTION: HHD

STUDY_SECTION_NAME: Healthcare and Health Disparities Study Section[HHD]


ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Project Narrative The heteromeric inwardly rectifying Kir4.1/Kir5.1 channels primary underlie the basolateral K+ conductance in the aldosterone-sensitive distal nephron. We propose that these channels are critical molecular determinants of electrolyte balance in the kidney and play an essential role in the mechanisms causing salt-sensitive hypertension and potassium imbalance. Herein, we will test this hypothesis using a combination of ex vivo and in vivo approaches, newly developed pharmacological tools and novel Kir4.1 and Kir5.1 knockouts generated on the background of the Dahl salt-sensitive rat.

PI_NAMEs: PALYGIN, OLEG  (contact)

PROGRAM_OFFICER_NAME: KETCHUM, CHRISTIAN J

PROJECT_TERMS: absorption;Affect;African American;Aldosterone;American;Attenuated;basolateral membrane;Blood;Blood Pressure;blood pressure control;Cardiorenal syndrome;Cardiovascular system;Cells;clinically relevant;Dahl Hypertensive Rats;Data;Development;Diet;dietary;Dietary Potassium;Dietary Supplementation;Distal;Distal convoluted renal tubule structure;Diuresis;Duct (organ) structure;Ductal Epithelial Cell;effective therapy;Electrolyte Balance;Electrolytes;epithelial Na+ channel;Event;Excretory function;experimental study;FDA approved;Generations;Genes;Genetic;high salt diet;Homeostasis;Hormones;Human;human disease;hyperkalemia;Hypertension;hypertensive;Hypokalemia;in vivo;Individual;inhibitor;insight;Ion Channel;Ions;Kidney;Knock-out;Mediating;Membrane Potentials;Mineralocorticoid Receptor;Modeling;Molecular;Natriuresis;Nephrons;Nortriptyline;novel;Pathology;Patients;Pharmaceutical Preparations;pharmacologic;Phenotype;Plasma;Play;Potassium;Potassium Channel;pressure;prevent;Publishing;Rattus;Regulation;renal damage;Renal function;Renin-Angiotensin-Aldosterone System;Reporting;Research Proposals;Rest;Risk;Role;salt intake;salt sensitive;salt sensitive hypertension;sensor;Serum;Severities;Side;Sodium;Sodium Chloride;symporter;Testing;tool;Tricyclic Antidepressive Agents;urinary;Water

PROJECT_TITLE: Role of basolateral K channels in renal salt handling and BP control


NIH_SPENDING_CATS: Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: Parkville

ORG_COUNTRY: AUSTRALIA

ORG_FIPS: AS

ORG_NAME: WALTER AND ELIZA HALL INST MEDICAL RES

PHR: Project narrative Latent Toxoplasma (which infects approximately 30% of the human population) are drug resistant and cause disease in the immunocompromised and progressive blindness in otherwise healthy individuals, leaving vulnerable patients without treatment options. Drug refractoriness likely occurs through changes in metabolism, and we show that these are intimately linked with differentiation into latent forms. We will show host nutritional signals activate Toxoplasma differentiation through a parasite metabolic pathway and key ubiquitination machinery, thus revealing how parasites sense environmental cues to activate latency.

PI_NAMEs: TONKIN, CHRIS  (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Acute;Amino Acids;Biochemical;Biology;Blindness;Brain;brain tissue;Carbon;Central Nervous System;Clinical;Complex;Country;CRISPR screen;Cues;Development;differentiation in vitro;Disease;Drug resistance;Environment;Enzymes;Exposure to;Genes;Genetic;Genetic Screening;Genetic Transcription;genome-wide;Glutamine;Human;Immunocompromised Host;in vivo;Individual;insight;latent infection;Life;Link;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Methodology;model organism;Muscle;Nutritional;Parasites;Pathogenesis;Patients;Pharmaceutical Preparations;Play;Population;Prevalence;programs;Proteomics;Publishing;Refractory;Regulation;Role;Signal Transduction;Source;Structure;Techniques;therapy resistant;Tissues;Toxoplasma;Translations;Ubiquitin;ubiquitin-protein ligase;Ubiquitination;whole genome;Work

PROJECT_TITLE: Regulation of latent stage differentiation through central carbon metabolism and ubiquitination


ADMINISTERING_IC: AA

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;Genetics;Neurosciences;Substance Misuse

ORG_CITY: RICHMOND

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: This project within the Integrative Neuroscience Initiative on Alcoholism-Neuroimmune consortium (INIA-N) will examine the molecular mechanisms by which excessive alcohol consumption alters the extracellular matrix in the brain and the function of the brain extracellular matrix in excessive alcohol drinking. Completing the aims of this project will contribute to fundamental knowledge of the effects of chronic excessive alcohol drinking on the brain and potentially lead to new therapeutic targets for the treatment of alcohol use disorder.

PI_NAMEs: LASEK, AMY WOLVEN (contact)

PROGRAM_OFFICER_NAME: LORANG-LEINS, DOMINIQUE

PROJECT_TERMS: alcohol abuse therapy;Alcohol consumption;alcohol exposure;alcohol testing;alcohol use disorder;Alcoholism;Alcohols;Antibodies;Astrocytes;Automobile Driving;Behavioral;Binding;binge drinking;Brain;brevican;cellular targeting;chromatin immunoprecipitation;Chronic;chronic alcohol ingestion;Collaborations;conditional knockout;Darkness;Data;Data Set;Digestion;DNA sequencing;drinking;drinking behavior;Ethanol;Ethanol dependence;Excitatory Synapse;experimental study;Extracellular Matrix;Extracellular Matrix Proteins;Gene Expression;Genes;genetic regulatory protein;Genetic Transcription;Glycosaminoglycans;Heavy Drinking;immune activation;Immune response;Immunologic Receptors;Interneurons;knock-down;Knowledge;Lentivirus;LoxP-flanked allele;Measures;Mediator;Modeling;Molecular;Mus;Neuroimmune;Neurons;Neurosciences;new therapeutic target;Parvalbumins;Phosphorylation;Prefrontal Cortex;Process;promoter;Proteins;Proteome;Proteomics;Protocols documentation;receptor;Receptor Signaling;Regulation;Research Personnel;Resolution;Role;Sampling;short hairpin RNA delivery;Stat3 protein;Structure;superresolution microscopy;Synapses;Synaptic plasticity;Testing;transcription factor;transcriptome;transcriptomics;Translating;vapor;Viral;whole genome

PROJECT_TITLE: 4/11 Neuroimmune and extracellular matrix interactions in alcohol consumption


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Breast Cancer;Cancer;Lung;Women's Health Research

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

PHR: Project Narrative After metastasis to the lungs, breast cancer cells are exposed to unique forces and matrix proteins that are not present at the primary tumor. My previous findings indicate that cyclic stretching, mimicking breathing dynamics within a 3D model of the early metastatic niche, can drive tumor cells into a state of growth arrest without widespread cell death. Because stromal cells are the key contributor of matrix composition and architecture, my goal is to evaluate the unique fibroblast subtypes conditioned by breast cancer cells at different stages of the metastatic cascade and characterize how the tissue changes they produce alter the metastatic progression of disseminated breast cancer cells.

PI_NAMEs: LIBRING, SARAH  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: 3-Dimensional;Apoptosis;Architecture;Atomic Force Microscopy;Biomimetics;Breast Cancer Cell;Breathing;Cancer Biology;cancer cell;Cancer Cell Growth;cancer diagnosis;cancer subtypes;Cell Death;Cell model;Cell secretion;cell type;Cells;Cessation of life;Clinical;Communication;Complex;conditioning;Coupled;defined contribution;Desmoplastic;Development;Disease;Doctor of Philosophy;Educational process of instructing;effective therapy;Endocrine;Engineering;Epithelium;experimental study;Exposure to;extracellular;Extracellular Matrix;extracellular vesicles;Fibroblasts;Fibronectins;Flow Cytometry;Foundations;Glycoproteins;Goals;Growth;improved;in vivo;insight;interest;Lead;Link;Lung;lung volume;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;mechanical force;mechanical load;mechanical properties;Mechanics;mechanotransduction;Mentors;Mesenchymal;metabolic rate;Metastatic breast cancer;Metastatic Neoplasm to the Lung;Methods;migration;Modeling;Morbidity - disease rate;mortality;Neoplasm Metastasis;neoplastic;neoplastic cell;Nonmetastatic;novel;Output;paracrine;Pathway interactions;Patients;Periodicity;Phenotype;phenotypic biomarker;Positioning Attribute;Postdoctoral Fellow;prevent;Primary Neoplasm;Production;Proliferating;Proteins;Proteomics;Research;Research Personnel;Role;Signal Transduction;single-cell RNA sequencing;Site;skills;Stretching;Stromal Cells;Structure of parenchyma of lung;Survival Rate;targeted treatment;Testing;therapy development;three dimensional cell culture;three-dimensional modeling;Tissue Engineering;Tissues;Training;transmission process;Tumor Cell Migration;tumor microenvironment;Universities;Vesicle;Western Blotting;Woman;Work

PROJECT_TITLE: Matrix Accumulation in the Metastatic Niche


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: ANN ARBOR

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: PROJECT NARRATIVE This study will assess the clinical effectiveness and environmental impact of metered-dose vs dry-powder inhalers. The study will also assess patient and facility factors associated with a successful inhaler device conversion. The results will inform guidelines and policy to optimize control of common respiratory diseases while reducing the environmental impact of the care provided.

PI_NAMEs: PRESCOTT, HALLIE CHRISTINE (contact);RABIN, ALEXANDER SOLOMON

PROJECT_TERMS: Accounting;Address;Adrenal Cortex Hormones;Adult;Aerosols;Affect;Agonist;Albuterol;Asthma;Carbon Dioxide;care delivery;Caring;Chronic;Chronic Obstructive Pulmonary Disease;climate change;climate impact;climate-related health;Clinical;clinical decision-making;Clinical effectiveness;cohort;Communication;comparative effectiveness;Data;Devices;disorder control;Dose;Drug Delivery Systems;Dryness;Economics;Education;Effectiveness;Emergency department visit;Environmental Impact;evidence based guidelines;Formularies;Future;Gases;Global Warming;Goals;greenhouse gases;Guidelines;Health;health care service utilization;Healthcare;Healthcare Systems;Hospitalization;improved;Inhalation;Inhalators;innovation;Interview;Life Cycle Stages;Lung;Marketing;meter;Metered Dose Inhaler Device;Methods;National Formulary;Natural experiment;Outcome;Patient Education;Patients;Persons;Pharmaceutical Preparations;Phase;Policies;Powder dose form;Prednisone;pressure;propellant;Research Design;respiratory;Respiratory Disease;Retrospective cohort;Severity of illness;Structure;Surveys;Testing;Treaty;United States Department of Veterans Affairs;Update;Veterans;Veterans Health Administration

PROJECT_TITLE: Veterans Affairs Study of a Real-World Inhaler Delivery Device Transition on Climate and Health Outcomes (VA-SWITCH)

STUDY_SECTION_NAME: HSR-1 Health Care and Clinical Management[HSR1]


ORG_CITY: PITTSBURGH

PHR: Implementation science aims to bridge the 17-year gap between research evidence and real-world healthcare practice, which has led to low-quality, inequitable medical care. However, this burgeoning discipline still lacks empirical and efficient methods to guide three central processes: 1) to identify implementation barriers; 2) to systematically track which strategies work to improve care; and 3) to provide accessible data and expert rec- ommendations to guide implementation strategy selection for use in research and practice. Project OASIS (Op- timizing Approaches to Select Implementation Strategies) is uniquely poised to address these three critical gaps in the science of implementation. Using our team of experts and 38-project years of data, this research will lead to 1) a decision aid to guide researchers and clinicians selecting among 73 strategies to address di- verse health care issues, and data collection tools to further advance the science of 2) measuring implementa- tion barriers and 3) tracking implementation strategies.

PI_NAMEs: CHINMAN, MATTHEW ;ROGAL, SHARI S (contact)

PROJECT_TERMS: Address;Adoption;Agreement;Algorithms;arm;Caring;Cessation of life;Characteristics;chemotherapy;Clinic;Clinical;Cluster randomized trial;Code;Complex;computerized;Consolidated Framework for Implementation Research;Consumption;Data;Data Analyses;Data Collection;data resource;Data Set;Decision Aid;Decision Making;Discipline;Effectiveness;Equitable healthcare;Equity;evidence base;evidence based guidelines;Evidence based practice;experience;Expert Opinion;Failure;Future;Goals;health care delivery;health care disparity;health equity;Healthcare;Hospitals;Hybrids;implementation barriers;implementation efforts;implementation evaluation;implementation facilitators;implementation measures;implementation research;implementation science;implementation strategy;improved;Individual;Inequity;innovation;Interview;Knowledge;Leadership;Letters;Machine Learning;Measures;Medical;Medicine;Methodology;Methods;Output;Performance;precision oncology;prevent;Process;Property;Psychometrics;Public Health;Quality of Care;Randomized;Recommendation;Research;Research Personnel;Risk;Science;Screening for Hepatocellular Cancer;Site;Structure;Survey Methodology;Surveys;Taxonomy;Techniques;Testing;theories;Time;tool;Trees;United States;uptake;usability;user centered design;Vertebral column;Veterans;web site;Work;World Health

PROJECT_TITLE: Project OASIS: Optimizing Approaches to Select Implementation Strategies

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