NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Digestive Diseases;Esophageal Cancer;Genetics;Human Genome;Lung;Lung Cancer;Rare Diseases;Skin Cancer;Tobacco;Tobacco Smoke and Health

ORG_CITY: GRAND RAPIDS

ORG_NAME: VAN ANDEL RESEARCH INSTITUTE

ORG_STATE: MI

PHR: PROJECT NARRATIVE: In this project, we will employ new methodologies for DNA damage analysis with the goal of mapping specific DNA damage genome-wide and at the nucleotide level of resolution. The first and second Aims will apply the new methodology for testing hypotheses that two specific types of DNA damage are linked to mutational signatures in human liver cancers and esophageal cancers, respectively, and the last Aim is devoted to understanding the mechanisms of tobacco carcinogen-induced mutations.

PI_NAMEs: PFEIFER, GERD P (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: 8-oxo-dGTP;adduct;Adenine;Aldehydes;Aromatic Polycyclic Hydrocarbons;Base Sequence;cancer genome;cancer type;Carcinogens;Cell Culture System;Characteristics;Cytosine;Dependence;DNA;DNA Adducts;DNA Damage;DNA lesion;DNA Methylation;DNA Repair;DNA Sequence;dominant genetic mutation;environment related cancer;Environmental Exposure;Enzymes;Esophageal Adenocarcinoma;Esophagus;Etiology;Event;Felis catus;Frequencies;Future;Genes;Genetic Transcription;Genome;genome sequencing;genome-wide;Geography;Goals;Guanine;Human;Human Genome;Induced Mutation;Inflammation;insight;Knowledge;Lesion;Link;Lipid Peroxidation;Lung;Malignant neoplasm of esophagus;Malignant neoplasm of liver;Malignant neoplasm of lung;Malignant Neoplasms;Maps;Measures;Melanoma;method development;Methodology;Methods;mouth squamous cell carcinoma;Mutagenesis;Mutate;Mutation;Mutation Analysis;mutation assay;Names;Nucleotides;Oxidative Stress;Pathologic;Pathway interactions;Pattern;Play;Positioning Attribute;Procedures;Process;Rare Lesion;rare variant;Resolution;Role;Science;Skin Carcinoma;Smoker;Smoking;Somatic Mutation;Source;Specificity;sunlight-induced;Technology;Testing;Tissues;Tobacco;Tobacco smoke;tobacco user;Tobacco-Associated Carcinogen;Tobacco-Related Carcinoma;transversion mutation;tumor;Work

PROJECT_TITLE: Mechanisms of cancer mutations

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Cancer;Chronic Liver Disease and Cirrhosis;Complementary and Integrative Health;Dietary Supplements;Digestive Diseases;Liver Cancer;Liver Disease;Nanotechnology;Rare Diseases

ORG_CITY: DALLAS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_FIPS: US

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE Locoregional delivery of docosahexaenoic acid (DHA) loaded lipoproteins, a completely natural engineered biologic, is able to selectively kill liver tumor cells at doses that do not harm surrounding normal liver. In the present proposal, we aim to leverage the selectivity of this agent to treat liver cancer without injury to the surrounding liver in the setting liver cirrhosis. In addition, we will assess the efficacy of this biologic to provide sustained tumor eradication over conventional locoregional therapies. This project is in response to the parent NIH R01 funding opportunity announcement PA20-185.

PI_NAMEs: CORBIN, IAN RONALD (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: Acute;Address;Aftercare;angiogenesis;anti-cancer;Antitumor Response;Biological;biomaterial compatibility;Biomedical Engineering;Cancer Etiology;Catheterization;Cessation of life;Chemoembolization;Cirrhosis;Clinic;clinical practice;Compensation;Consumption;Curative Surgery;Data;Deterioration;Development;Diagnosis;dietary;Disease;Docosahexaenoic Acids;Dose;effective therapy;Effectiveness;efficacy evaluation;Engineering;epithelial to mesenchymal transition;Etiology;Extensive Necrosis;feeding;Fluoroscopy;Funding Opportunities;Goals;Growth;Hepatic;Hepatic artery;Hepatocyte;hepatoprotective;High Dose Chemotherapy;high risk population;Histopathology;Human;Hypoxia;image guided;improved;in vivo;Incidence;Injury;innovation;Intervention;Ischemia;ischemic injury;Light;Lipoprotein (a);Liver;liver cancer model;Liver Cirrhosis;Liver diseases;liver function;liver injury;Liver neoplasms;liver preservation;Low-Density Lipoproteins;Malignant Epithelial Cell;Malignant neoplasm of liver;Malignant Neoplasms;Measures;Mediating;Medicine;Metabolism;Methods;Modeling;Molecular;nanoparticle;Necrosis;neoplastic cell;novel;novel therapeutics;Omega-3 Fatty Acids;Palliative Care;Parents;patient derived xenograft model;patient population;Patients;Perfusion;Population Heterogeneity;Primary carcinoma of the liver cells;Process;Property;Radiology Specialty;Rattus;reconstitution;Recurrent tumor;Research Proposals;Residual Neoplasm;Resolution;response;Risk Reduction;Rodent;Safety;Signal Transduction;Solid Neoplasm;Surveillance Program;Survival Rate;Technology;Testing;Therapeutic;Toxic effect;Treatment Efficacy;treatment strategy;tumor;Tumor Burden;tumor eradication;tumor growth;United States;United States National Institutes of Health;Unresectable;uptake;Vascular Endothelial Growth Factors;Work

PROJECT_TITLE: Docosahexaenoic Acid Loaded Low-density Lipoproteins: A Novel Biologic Intervention for Hepatocellular Carcinoma.


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Dental, Oral, and Craniofacial Disease;Neurosciences

ORG_CITY: PORTLAND

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Management of tumors at the skull base has been clinically challenging for over a century as they are typically located deep in the skull and are routinely associated with critical neurovascular structures, where damage leads to high morbidity and mortality. While neuroanatomical knowledge, white light visualization and neurophysiolog-ical monitoring are utilized in concert to preserve the cranial nerves, nerve damage and incomplete resection continue to challenge skull base surgeries. Intraoperative nerve-specific imaging using a cranial nerve specific fluorescent probe would significantly improve nerve identification and visualization, providing an immediate ben-efit to patients and surgeons.

PI_NAMEs: GIBBS, SUMMER LYNNE (contact)

PROGRAM_OFFICER_NAME: KUMSA, DOE WONDWOSSEN

PROJECT_TERMS: Address;Adverse effects;Animal Model;Biodistribution;Biological;Blood;Blood - brain barrier anatomy;Blood Vessels;blood-brain barrier crossing;blood-brain barrier permeabilization;Central Nervous System;Chronic;Clinical;Clinical Medicine;clinical translation;Color;Cranial Nerves;cranium;design;Development;Dose Limiting;Drug Kinetics;Evaluation;Excision;FDA approved;Fluorescein;Fluorescence;fluorescence-guided surgery;Fluorescent Probes;fluorophore;Formulation;Fright;functional improvement;Future;Goals;Health;Hour;Iatrogenesis;Image;imaging system;improved;Indocyanine Green;Infrastructure;Injury;Knowledge;Lead;Libraries;Light;meningioma;Methods;Methylene blue;Microscope;minimally invasive;Modeling;Monitor;Morbidity - disease rate;mortality;Motor disability;Nerve;nerve damage;nerve injury;nerve repair;Nerve Tissue;Neurilemmoma;Neuroanatomy;Neuropathy;neurophysiology;neurosurgery;neurovascular;novel;Operative Surgical Procedures;Optics;Patients;Peripheral Nervous System;Pharmacodynamics;Pharmacology and Toxicology;Photoaffinity Labels;pre-clinical;preservation;prevent;Property;Quality of life;Risk;Rodent;Sensory disabilities;skull base;Skull Base Neoplasms;small molecule;Source;Specificity;Structure;Structure-Activity Relationship;Surgeon;surgery outcome;Surgical complication;Surgical Pathology;Surgical Specialties;System;Technology;Testing;Therapeutic;Tissues;Toxic effect;Toxicology;Translating;Translations;tumor;Visualization;Work

PROJECT_TITLE: Fluorescence Guided Surgery using Near Infrared Nerve-specific Probes for Cranial Nerve Preservation

STUDY_SECTION: IPCA

STUDY_SECTION_NAME: Imaging Probes and Contrast Agents Study Section[IPCA]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Brain Disorders;Fragile X Syndrome;Genetics;Intellectual and Developmental Disabilities (IDD);Machine Learning and Artificial Intelligence;Mental Health;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE: Cortical interneurons are understudied in Fragile X Syndrome. We will perform a multilevel analysis of interneuron dysfunction in Fmr1-/- mutants from cell subtype spatial distribution to fine grained synaptic levels.

PI_NAMEs: AU, EDMUND  (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: 3-Dimensional;Address;Animals;Atlases;autism spectrum disorder;automated segmentation;Axon;Brain;Cell Count;cell type;Cells;Cerebral cortex;CGG repeat;Clinical;Cluster Analysis;comorbidity;confocal imaging;Consensus;Data;Defect;Dendrites;Dendritic Spines;density;developmental disease;Disease;Distal;epigenetic silencing;Etiology;excitatory neuron;Excitatory Synapse;FMR1 gene;Fragile X Syndrome;Functional disorder;Future;Genetic;Grain;hippocampal pyramidal neuron;Human;Image;in vivo;Individual;inhibitory neuron;Inhibitory Synapse;innovation;Intellectual functioning disability;Interneurons;Investigation;Knock-out;Knockout Mice;learning strategy;Link;Long-Term Potentiation;Machine Learning;machine learning pipeline;Measures;Mental Depression;Messenger RNA;Methods;Modeling;mouse model;multilevel analysis;Mus;mutant;Mutant Strains Mice;Myoepithelial cell;Neurodevelopmental Disorder;neuronal cell body;Neurons;novel;novel strategies;Patients;Periodicity;Phenotype;Play;Population;postsynaptic;preference;Presynaptic Terminals;Probability;Regulation;Resolution;RNA-Binding Proteins;Role;Schizophrenia;Sensory;single cell analysis;single-cell RNA sequencing;Spatial Distribution;Specificity;Standardization;Stereotyping;Structure;Synapses;synaptic function;Techniques;Testing;unsupervised clustering;Work

PROJECT_TITLE: Multilevel Analysis of Cortical Interneuron Dysfunction in Fragile X Syndrome


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;Biomedical Imaging;Brain Disorders;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative As the burden of neurodegenerative diseases in the United States and worldwide is high, there is a critical need to utilize novel PET ligands to image illness-related biological processes in the brain. This work will develop key imaging tools to study ionotropic glutamate receptors signaling pathway and advance our understanding of its role in the pathophysiology of Alzheimer’s disease.

PI_NAMEs: LIANG, STEVEN H (contact)

PROGRAM_OFFICER_NAME: PETANCESKA, SUZANA

PROJECT_TERMS: AD transgenic mice;Affinity;Age;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease therapeutic;Alzheimer's disease therapy;Amyloid beta-Protein;Animals;APP-PS1;Applications Grants;Astrocytes;Binding;Biological Process;Brain;Brain region;Characteristics;Chronic;Clinical Research;Clinical Trials;cohort;Correlation Studies;CSF1R gene;cytokine;design;Development;Disease;disease model;disease phenotype;Disease Progression;drug development;drug discovery;Economic Burden;efficacious treatment;excitotoxicity;Foundations;Functional disorder;Glutamate Receptor;Glutamates;Goals;healthy volunteer;Human;Image;Imaging Device;imaging study;Incidence;Inflammatory;inhibitor;Kinetics;Knowledge;Life Expectancy;Ligands;longitudinal positron emission tomography;Maps;Measurement;Mediating;Medical;Memantine;Microglia;molecular imaging;Monitor;mouse model;Mus;N-Methyl-D-Aspartate Receptors;Neurodegenerative Disorders;Neuroimmune;neuroinflammation;neuron loss;neurotoxicity;non-invasive imaging;novel;Observational Study;Outcome;outcome prediction;Pathogenesis;Pathologic;Pharmaceutical Preparations;Positron-Emission Tomography;pre-clinical;Process;Receptor Signaling;Role;Signal Pathway;Signal Transduction;Societies;Symptoms;Synapses;Testing;Time;tool;Tracer;Transgenic Organisms;Treatment Efficacy;treatment response;United States;Work

PROJECT_TITLE: PET imaging of ionotropic glutamate receptor signaling in Alzheimer's disease

STUDY_SECTION: EITN

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


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Nutrition;Obesity

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: Project Narrative Obesity is an important public health problem and linked to metabolic disorders including diabetes, cardiovascular diseases, kidney diseases, and cancer. This research seeks to understand basic mechanisms of adaptive thermogenesis and to identify new ways to treat or prevent obesity.

PI_NAMEs: SUN, YIZHI  (contact)

PROGRAM_OFFICER_NAME: LYNCH, CHRISTOPHER

PROJECT_TERMS: Ablation;Acceleration;Address;adipocyte biology;Adipocytes;Adipose tissue;Advisory Committees;Alkaline Phosphatase;Amino Acid Sequence;Animals;Area;Automobile Driving;Binding Proteins;Biochemical;Biological;Biology;Biophysics;Cardiovascular Diseases;career;Cells;cellular imaging;Chemicals;Consumption;Creatine;Cysteine;Dana-Farber Cancer Institute;Data;Diabetes Mellitus;diet-induced obesity;Disease;Doctor of Philosophy;Elements;Energy Metabolism;Ensure;Environment;Event;Fatty acid glycerol esters;Fatty Liver;Futile Cycling;gain of function;Generations;Genes;Genetic;genetic approach;Goals;Hydrolysis;imaging approach;imaging study;Immunoprecipitation;innovation;Kidney Diseases;Laboratories;Laboratory Research;Link;Malignant Neoplasms;Mediator;Medical;medical schools;Membrane Microdomains;Metabolic;metabolic abnormality assessment;Metabolic Diseases;Metabolism;Methods;Mitochondria;Mitochondrial Proteins;Molecular;Mouse Strains;Mus;Muscle Fibers;Mutation Analysis;novel;Obesity;obesity prevention;obesity treatment;operation;Oxidative Phosphorylation;Pathway interactions;pharmacologic;Phosphocreatine;Phosphorylation;Physiological;Play;polypeptide;Post-Translational Protein Processing;Prevention;Process;Protein Dephosphorylation;protein transport;Proteins;Proteome;Proteomics;Public Health;Reactive Oxygen Species;red fluorescent protein;Regulation;Reporter;Research;Research Personnel;Respiration;Role;Signal Transduction;Specificity;Testing;Therapeutic;therapeutic target;Thermogenesis;Tissue Engineering;Tissues;trafficking;Transgenic Mice;Transportation;Travel;Variant;Visualization;Work

PROJECT_TITLE: The Role of Mitochondrial TNAP in Adaptive Thermogenesis

STUDY_SECTION: DDK

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


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Nonembryonic - Human

ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: Project Narrative Glioblastoma (GBM) is the most frequent and lethal type of primary brain tumor that is highly resistant to current treatments including immune checkpoint blockade (ICB), indicating that development of new effective therapeutic approaches is urgently needed. Because GBM harbors abundant tumor-associated macrophages (TAMs) that mainly augment malignant growth, promote therapeutic resistance, and mediate immune suppression that negatively impacts current immunotherapy, reprograming tumor-promoting macrophages (pTAMs, M2-like) into tumor-suppressive macrophages (sTAMs, M1-like) not only activates macrophage phagocytosis of glioma cells to suppress malignant growth but may also remodel the immune microenvironment to facilitate current ICB. In this proposal, we will assess whether reprograming pTAMs into sTAMs through BACE1 inhibition by MK-8931 synergizes with current ICB to significantly improve therapeutic efficacy for GBM, which will inform further clinical trials to potentially benefit patients with GBM or other malignant brain tumors including brain metastases.

PI_NAMEs: BAO, SHIDENG  (contact)

PROGRAM_OFFICER_NAME: SINGH, ANJU

PROJECT_TERMS: Alzheimer's Disease;beta-site APP cleaving enzyme 1;Biological Assay;cancer therapy;CD34 gene;Cells;checkpoint inhibition;Clinical Trials;Combined Modality Therapy;cytokine;design;Development;Dose;drug candidate;Engraftment;Future;Glioblastoma;Glioma;Growth;Hematopoietic stem cells;Human;humanized mouse;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;Immunosuppression;Immunotherapy;improved;induced pluripotent stem cell;Infiltration;inhibitor;Label;Low Dose Radiation;Macrophage;Malignant - descriptor;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;Metastatic malignant neoplasm to brain;Modeling;Molecular;Molecular Target;Mus;Nature;novel therapeutic intervention;Outcome;Patients;Phagocytosis;pharmacologic;preclinical study;Primary Brain Neoplasms;Prognosis;programs;Resistance;screening;small molecule;stem cells;synergism;T-Lymphocyte;Therapeutic;therapeutic target;therapeutically effective;therapy resistant;Treatment Efficacy;tumor;tumor growth;tumor microenvironment;Tumor Promotion;Tumor-associated macrophages;tumor-immune system interactions;Xenograft procedure

PROJECT_TITLE: Macrophage-based Therapy and Immune Checkpoint Blockade for Glioblastoma

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


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

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

ORG_CITY: LINCOLN

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF NEBRASKA LINCOLN

ORG_STATE: NE

PHR: PROJECT NARRATIVE The proposed research will examine how discrimination stress affects a range of chronic disease outcomes, and how social relationships may buffer these effects to increase resilience in a social system. It will yield new knowledge and ultimately new interventions for how to best utilize social support structures in the context of recurrent discrimination stress with implications for several chronic health concerns that are leading causes of death in the U.S., such as cardiovascular disease.

PI_NAMEs: ANDREWS, ARTHUR  (contact)

PROGRAM_OFFICER_NAME: GARRIDO, CARLOS OSWALDO

PROJECT_TERMS: acute stress;Address;Adrenal Glands;Affect;allostasis;allostatic load;Attenuated;biological adaptation to stress;Biological Markers;Black race;Bluetooth;Buffers;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder risk;Cause of Death;Chronic;Chronic Disease;Chronic stress;Cities;contagion;Data;Data Reporting;design;Detection;diaries;Disadvantaged;Discrimination;Disease Outcome;Disparate;Ethnic Origin;experience;Exposure to;Frequencies;Goals;Health;Health Benefit;health disparity;health inequalities;Hispanic;Hispanic Populations;Hypothalamic structure;Immigrant;Individual;Inflammation;insight;Intervention;Interview;Knowledge;Life Expectancy;Link;Measures;Mental disorders;Modeling;National Institute on Minority Health and Health Disparities;Network-based;new technology;novel;novel strategies;Outcome;Participant;Pathway Analysis;Patient Self-Report;perceived discrimination;Persons;Phase;Pituitary Gland;Population;Prevalence;promote resilience;Protocols documentation;psychosocial;Recovery;recruit;Recurrence;Regulation;Reporting;Research;resilience;Respondent;response;Risk;risk prediction;Sampling;Science;social;Social Environment;Social Network;social relationships;Social support;Standardization;standardize measure;Stress;stress reactivity;stress reduction;stressor;Structural Models;Structure;support network;System;Technology;Testing;theories;transmission process;Work

PROJECT_TITLE: Allostatic load, Response to discrimination stress, Discrimination Exposure frequency, and social Network structure and function (ARDEN)


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: STILLWATER

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: OKLAHOMA STATE UNIVERSITY STILLWATER

ORG_STATE: OK

PHR: PROJECT NARRATIVE Idiopathic pulmonary fibrosis (IPF) afflicts approximately 3 million individuals worldwide, and an estimated 40,000 people succumb to the disease each year in the United States. Achieving the goals of this project will lead to the discovery of new molecules and pathways that modulate fibroblast activation and thus provide insights toward the development of effective therapies for IPF.

PI_NAMEs: LIU, LIN  (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: 3' Untranslated Regions;Actins;Advanced Development;Anemia;Area;Asbestos;Binding;Bleomycin;Chronic lung disease;cigarette smoke;Co-Immunoprecipitations;Development;Diagnosis;Disease;Down-Regulation;effective therapy;Elements;Etiology;Family;FDA approved;Fibroblasts;fibrotic lung;gain of function;gene therapy;Genes;Genetic;genetic manipulation;Genetic Transcription;genome-wide;Goals;homeodomain;Homeostasis;Human;idiopathic pulmonary fibrosis;In Vitro;in vivo;Individual;Inhalation;inhibitor;insight;Invaded;Ions;Iron;Iron Chelation;iron supplementation;Iron-Regulatory Proteins;kidney fibrosis;knock-down;loss of function;Lung;Mediating;member;Messenger RNA;Modeling;Molecular;mouse development;mouse model;mRNA Stability;Mus;Mutagenesis;Names;novel;overexpression;Particulate Matter;Pathogenesis;Pathway Analysis;Pathway interactions;Persons;Pharmaceutical Preparations;pharmacologic;pre-clinical;Process;Protein Kinase Interaction;Proteins;Pulmonary Fibrosis;Regulation;Ring Finger Domain;Risk Factors;Role;SH3 Domains;Signal Pathway;Smooth Muscle;solute;Stress Fibers;Testing;Translations;Treatment Efficacy;ubiquitin-protein ligase;Ubiquitination;United States;Up-Regulation

PROJECT_TITLE: The Role of Iron In Pulmonary Fibrosis

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


ORG_DEPT: PEDIATRICS

PHR: PROJECT NARRATIVE The aim of this project is to determine mechanism(s) by which neutrophils in cystic fibrosis airways contribute to increased chlorine bleach production by an enzyme called myeloperoxidase. We will use highly translational models of airway neutrophils and epithelial cells, test mechanisms including excessive secretion of myeloperoxidase (“hyperexocytosis”), validate our findings using clinical airway samples, and consider clinical variables such as use of CFTR modulators. We anticipate knowledge generated during this study will pave the way for rational anti-inflammatory and antioxidant therapies, filling current gaps in cystic fibrosis care and benefiting patients with related inflammatory lung diseases.

PI_NAMEs: CHANDLER, JOSHUA D (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Acute;Address;Age;airway epithelium;airway inflammation;analytical method;Anti-Inflammatory Agents;anti-microbial drug;antioxidant therapy;Antioxidants;autooxidation;Binding;Biological;Birth;Bronchiectasis;Caring;cell injury;Cell Survival;Cells;Chemotactic Factors;Chlorides;chlorination;Chlorine;Clinical;clinical development;Clinical Research;Cystic Fibrosis;cystic fibrosis airway;cystic fibrosis airway epithelia;cystic fibrosis patients;Cystic Fibrosis sputum;Cystic Fibrosis Transmembrane Conductance Regulator;Cytoplasmic Granules;cytotoxicity;Data;Defect;design;detection method;Disease;Disease Progression;drug development;early cystic fibrosis;Enzymes;Epithelial Cells;Epithelium;Event;Exhibits;Exocytosis;Experimental Designs;experimental study;extracellular;extracellular vesicles;Generations;Glucose;glucose production;Glutathione;Goals;healthspan;Human;Hydrogen Peroxide;Hypochlorous Acid;Immunobiology;immunoregulation;improved;In Vitro;Incubated;Inflammation;Inflammatory;inflammatory lung disease;inhibitor;Intervention;Knowledge;Label;Leukotriene B4;life span;Lung;Lung Diseases;lung injury;Mediating;Membrane Proteins;Metabolic;Metabolism;metabolomics;methionine sulfoxide;migration;Modeling;Molecular;Monitor;mortality;Mus;mutant;neutrophil;next generation;novel;Nutrient;Organ;Oxidants;oxidation;Oxidation-Reduction;Oxygen;pathogen;Pathway interactions;Patients;Peroxidases;pharmacologic;Phenotype;Physiological;Prevalence;Production;Proteins;Proteomics;Pseudomonas aeruginosa;Pulmonary Cystic Fibrosis;Pulmonary Inflammation;Pulmonary Pathology;rational design;Reaction;Reactive Oxygen Species;Research;research and development;Resistance;response;Role;Sampling;Series;Signal Transduction;Specimen;Sputum;Stains;standard of care;Staphylococcus aureus;targeted biomarker;targeted treatment;Testing;Therapeutic;Thiocyanates;Tissues;trafficking;translational model;Validation;Vesicle;VX-770

PROJECT_TITLE: Neutrophil hyperexocytosis and hypochlorous acid exposure in early cystic fibrosis lung disease

STUDY_SECTION: LCMI

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


NIH_SPENDING_CATS: Biomedical Imaging;Brain Cancer;Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Neurosciences;Precision Medicine;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROSURGERY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because developing a noninvasive capability of diagnosing and monitoring brain tumors in the brain will fundamentally advance personalized care for patients with malignant brain tumors. In addition to the standard diagnostics of anatomic imaging and surgical histology, the proposed technique has the potential to become the third pillar for brain tumor management by radically advancing the ability to easily and regularly acquire tumor genetic and molecular signatures.

PI_NAMEs: CHEN, HONG ;LEUTHARDT, ERIC CLAUDE (contact)

PROGRAM_OFFICER_NAME: TATA, DARAYASH B

PROJECT_TERMS: anatomic imaging;Animals;Apoptosis;Biological Markers;Biopsy;Blinded;Blood;Blood - brain barrier anatomy;Blood Circulation;blood-brain barrier disruption;blood-brain barrier permeabilization;Brain;Brain Neoplasms;Cancer Detection;Cancer Patient;Cardiovascular system;Cells;Cephalic;circulating biomarkers;Classification;Clinic;Clinical;Clinical Management;clinical practice;Clinical Research;Clinical Trials;clinically significant;Data;Data Analyses;detection sensitivity;Development;Devices;Diagnosis;Diagnostic;Disease;DNA;Drug Delivery Systems;Edema;Enrollment;Evaluation;Excision;Family suidae;Focused Ultrasound;Foundations;Frequencies;Future;Genetic;genetic information;genetic signature;Genomics;Glioblastoma;Goals;Green Fluorescent Proteins;Hemorrhage;Histologic;Histology;human data;Image;implantation;improved;inflammatory marker;Injury;innovation;Intervention;Intravenous;Knowledge;liquid biopsy;Location;Magnetic Resonance Imaging;Malignant neoplasm of brain;Measurement;Medical;Methods;Microbubbles;minimally invasive;Modeling;Molecular;Molecular Diagnosis;molecular marker;Molecular Profiling;Molecular Target;Monitor;Morbidity - disease rate;mouse model;Mutation;Mutation Detection;Necrosis;Neuronavigation;novel;Operative Surgical Procedures;Patients;personalized care;Plasma;porcine model;Procedures;Property;prospective;protein biomarkers;Public Health;Quality of Care;Quality of life;radiological imaging;Randomized;Research;Resected;Risk;RNA;Rodent;Safety;safety and feasibility;Sampling;Schedule;Site;Sonication;Specimen;Stains;System;targeted treatment;Techniques;Therapeutic;therapeutically effective;Time;tissue injury;Tissues;tool;Transfection;Translations;treatment response;tumor;tumor DNA;Tumor Markers;tumor progression;Tumor-Derived;Variant

PROJECT_TITLE: Sonobiopsy for Noninvasive Genetic Evaluation of Glioblastoma Patients

STUDY_SECTION: CBSS

STUDY_SECTION_NAME: Cancer Biomarkers Study Section[CBSS]


ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Patients with locally advanced cancers continue to be treated with radiotherapy and decades old conventional chemotherapies that sensitize tumors to radiation damage, however tumor control is suboptimal and treatment toxicity high. Based on preliminary data, we hypothesize that highly potent antibody drug conjugates specifically radiosensitize tumor cells, avoid normal tissue and engage tumor immune responses. In this proposal, we will investigate the interplay of antibody conjugated radiosensitizers and radiotherapy within the context of the tumor immune microenvironment to develop precision radio-chemo-immunotherapy strategies.

PI_NAMEs: ADVANI, SUNIL J (contact)

PROGRAM_OFFICER_NAME: PRASANNA, PAT G

PROJECT_TERMS: adaptive immune response;anti-tumor immune response;Antibodies;antibody conjugate;Antibody-drug conjugates;Binding;Cancer Model;Cancer Patient;carcinogenesis;Carcinogens;CD8-Positive T-Lymphocytes;Cell membrane;Cell Surface Receptors;Cells;Cetuximab;checkpoint inhibition;chemoradiation;chemotherapy;Clinical;clinically relevant;Coupled;curative treatments;cytotoxic;Cytotoxic agent;Cytotoxic Chemotherapy;cytotoxicity;Cytotoxin;Data;delivery vehicle;design;DNA Damage;DNA Repair;Dose Limiting;drug development;efficacy testing;Epidermal Growth Factor Receptor;ERBB2 gene;Goals;Grant;Immune;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;Immuno-Chemotherapy;Immunocompetent;immunodeficiency;immunogenic;Immunotherapy;Implant;improved;improved outcome;inhibitor;innovation;interest;Ionizing radiation;Irradiated tumor;Link;Locally Advanced Malignant Neoplasm;Modeling;Molecular;Morbidity - disease rate;mouse model;Mus;neoplastic cell;Normal tissue morphology;novel therapeutics;Organ;Pathway interactions;Patients;Pharmaceutical Preparations;pre-clinical;precision medicine;programmed cell death protein 1;Quality of life;Radiation induced damage;Radiation therapy;Radiation-Sensitizing Agents;Radio;Radiosensitization;receptor;receptor binding;response;Role;Schedule;success;Systemic Therapy;systemic toxicity;targeted delivery;Techniques;Technology;Testing;Therapeutic;Therapeutic Index;Time;Tissues;tool;Toxic effect;Trastuzumab;Treatment-related toxicity;Tubulin;tumor;tumor specificity;tumor xenograft;tumor-immune system interactions

PROJECT_TITLE: Spatially precise radio-chemo-immunotherapy using antibody conjugates

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ADMINISTERING_IC: OD

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

ORG_CITY: ITHACA

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: CORNELL UNIVERSITY

PHR: Project Narrative Neonates respond differently to chronic infection than adults, and we have shown that a possible reason is their underlying resistance to CD8+ T cell exhaustion. This proposal will identify the key gene regulatory pathways and metabolic factors that contribute to these age-related differences, allowing us to develop more effective strategies to protect individuals from chronic infections and cancer alike.

PI_NAMEs: MAYMI, VIVIANA ISABEL (contact)

PROGRAM_OFFICER_NAME: TANDON, RITESH

PROJECT_TERMS: acute infection;Adoptive Transfer;Adult;aerobic glycolysis;Affect;age difference;aged;Antigens;Behavior;Biological Assay;Bone Marrow;CD8-Positive T-Lymphocytes;cell age;Cell Compartmentation;Cells;Cellular biology;Cellular immunotherapy;Cellular Metabolic Process;Chronic;Chronic Disease;chronic infection;Clinical Data;cytokine;Data;design;Development;Disease;Effector Cell;Epigenetic Process;Etiology;exhaust;exhaustion;experimental study;extracellular;extracellular vesicles;Family;Fetal Liver;Flow Cytometry;Foundations;Genes;Genus Hippocampus;Glycolysis;Glycolysis Inhibition;Hematologic Neoplasms;Hematopoietic stem cells;Heterogeneity;Human;Immunity;immunopathology;Immunotherapy;imprint;Individual;Infant;Infection;innovation;insight;Interferon Type II;Life;life span;Lymphocytic choriomeningitis virus;Malignant Neoplasms;Measures;Mediating;Memory;Metabolic;metabolic profile;Metabolism;metabolomics;MicroRNAs;Molecular;mouse model;Neonatal;Neonatal Mortality;neonate;novel;overexpression;Oxidative Phosphorylation;pathogen;Pathway interactions;patient response;Patients;pharmacologic;Phenotype;Physiological;Play;Predisposition;Production;programmed cell death protein 1;programs;Proliferating;protective pathway;Regulation;Regulatory Pathway;Repression;Resistance;Respiratory Tract Infections;response;RNA-Binding Proteins;Role;Source;System;T cell response;T-Lymphocyte;Testing;Therapeutic;transcriptome sequencing;tumor;Virus Diseases;Work

PROJECT_TITLE: Regulation of CD8+ T cell exhaustion by let-7/Lin28b in different stages of life


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Dental, Oral, and Craniofacial Disease;Social Determinants of Health

ORG_DEPT: DENTISTRY

ORG_NAME: NEW YORK UNIVERSITY

PHR: Project Narrative The proposed summer research education program is relevant to public health because it focuses on developing a diverse cohort of future oral health scientists. Once the workforce of oral health scientists becomes more representative of the United States population, there is the potential for significant reduction in oral health disparities. Thus, the proposed summer research education program is relevant to the part of NIH’s mission that pertains to promoting diversity in the extramural scientific workforce.

PI_NAMEs: BURNS, LOREL E (contact);LACRUZ, RODRIGO S.

PROGRAM_OFFICER_NAME: MCGUIRL, MICHELE

PROJECT_TERMS: Academy;Achievement;Admission activity;Advisory Committees;Behavioral Research;Biomedical Research;career;career development;Clinical Research;cohort;college;Country;craniofacial;Dental;Dental Schools;Dentistry;design;Development;didactic education;Education;education research;Educational Curriculum;Educational Status;effectiveness evaluation;Enrollment;Evaluation;experience;Exposure to;Extramural Activities;Faculty;faculty mentor;Fostering;Future;Goals;hands on research;health disparity;Health Occupations;Health Personnel;Health Professional;Health Promotion;Health Sciences;Healthcare;high school;improved;Individual;innovation;interest;Laboratories;meetings;Mentorship;Mission;Mouth Diseases;National Institute of Dental and Craniofacial Research;New York;Oral health;Outcome;Participant;Pathway interactions;Patient Recruitments;Population;pre-clinical;Program Evaluation;programs;Public Health;Readiness;Recommendation;recruit;Research;Research Methodology;Research Personnel;responsible research conduct;retention rate;Role;Schools;Science;Scientist;Seasons;skills;Smiling;social health determinants;Strategic Planning;Students;summer program;summer research;Training;training opportunity;Translational Research;undergraduate student;Underrepresented Minority;Underrepresented Populations;United States;United States National Institutes of Health;Universities;Writing

PROJECT_TITLE: Research Education in Oral Health Sciences


ADMINISTERING_IC: AR

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: HUNTSVILLE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF ALABAMA IN HUNTSVILLE

ORG_STATE: AL

PHR: PROJECT NARRATIVE The objective of this proposal is to improve outcomes in cartilage restoration and repair. The development of therapies to address cartilage repair and restoration to prevent further deterioration is poised to have a significant clinical impact.

PI_NAMEs: SUBRAMANIAN, ANURADHA  (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Acoustics;Address;American;articular cartilage;Attention;attenuation;Biochemical;Biological;biomechanical test;Biomechanics;Cadaver;Cartilage;Cartilage injury;cartilage regeneration;cartilage repair;Chondrocytes;Chondrogenesis;chondroprotection;Clinical;clinical application;clinically relevant;comparison control;computer grid;conditioning;Contralateral;cost estimate;Coupled;cytokine;Data;Data Aggregation;Defect;Degenerative polyarthritis;Deterioration;Development;Elements;Engineering;Environment;experimental study;Fibrocartilages;Frequencies;functional improvement;functional outcomes;Growth Factor;Histologic;Human;Hyaline Cartilage;Impairment;implantation;improved;improved outcome;In Situ;In Vitro;in vivo;Inferior;Inflammatory;inflammatory milieu;innovation;joint function;joint inflammation;Joints;Knee joint;Magnetic Resonance Imaging;mesenchymal stromal cell;Methods;minimally invasive;Modality;Modeling;Morbidity - disease rate;Non-linear Models;Oryctolagus cuniculus;Outcome;Pathway interactions;Phase;Phenotype;Phosphorylation Inhibition;preconditioning;prevent;Procedures;Property;Publishing;Regenerative capacity;Regimen;repaired;response;restoration;Sheep;sheep model;Site;System;Therapeutic;therapy development;Tissues;transcriptome sequencing;transcriptomic profiling;Translations;treatment group;Ultrasonic Therapy;Ultrasonic Transducer;ultrasound;Work

PROJECT_TITLE: Optimizing Ultrasound Regimens for Achieving Cartilage Repair

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


ADMINISTERING_IC: DA

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Drug Abuse (NIDA only);Opioid Misuse and Addiction;Opioids;Rural Health;Substance Misuse

ORG_NAME: BERKSHIRE BIOMEDICAL CORPORATION

PHR: NARRATIVE The Computerized Oral Prescription Administration System (COPATM) device is being developed as an automated oral liquid dispensing system for at-home methadone maintenance therapy (MMT). The COPA device has a major application to at-home MMT based upon the device's innovative dual biometric confirmation of both the patient's fingerprint and dentition before delivery of drug to the Intended User.

PI_NAMEs: TIMBERLAKE, JOHN  (contact)

PROGRAM_OFFICER_NAME: KOSTOV, YORDAN VALTCHOV

PROJECT_TERMS: Acceleration;Address;adverse outcome;Authorization documentation;Biometry;Clinic;Communication;Communities;Computer software;computerized;COVID-19 pandemic;Database Management Systems;Death Rate;Dentition;design;Development;Devices;disease transmission;Documentation;Dose;Drug Delivery Systems;Drug Metabolic Detoxication;effective therapy;Electronic Mail;Employment;Engineering;Enrollment;Ensure;Feedback;Fingerprint;Fright;Health;Healthcare;Hepatitis;HIV;Home;Human;improved;innovation;Liquid substance;Maintenance;manufacture;manufacturing organization;Marketing;member;Methadone;methadone treatment;Modality;Monitor;Notification;novel;Opiate Addiction;Opioid;opioid epidemic;opioid injection;opioid treatment program;opioid use;opioid use disorder;Oral;pandemic disease;Patients;Pattern;Performance;Pharmaceutical Preparations;Physicians;Pilot Projects;Production;Productivity;prototype;Qualifying;Quality of life;Remote management;remote monitoring;Reporting;Rights;Rural;rural counties;Secure;social;Societies;synthetic opioid;System;Technology;Testing;Text;Time;tool;United States Food and Drug Administration;United States Substance Abuse and Mental Health Services Administration;Validation;Work

PROJECT_TITLE: COPA, an Automated Medication Dispensing and Remote Management System for at Home Methadone Dispensing


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

ORG_DEPT: PHARMACOLOGY

PHR: New research in animal models suggest that neuronal insulin resistance disrupts insulin signaling and glucose utilization by the hippocampal neurons that regulate cognition and contribute to the pathogenesis of diseases associated with age-related cognitive impairment such as Alzheimer’s Disease (AD). WNK1/OSR1 kinases cross-talk with the insulin signaling pathway and are associated with diseases exhibiting cognitive dysfunction, yet, the underlying mechanistic detail by which WNK1/OSR1 signaling mediates insulin-dependent glucose uptake by the hippocampus and leads to the development of cognitive decline remain to be fully elucidated. To address this problem, the proposed work will combine kinase signaling biology, cell biology, metabolic and neurobehavioral physiology approaches to reveal the hippocampal WNK1/OSR1-dependent mechanisms by which insulin signaling mediates glucose metabolism and cognitive processes which go awry in insulin resistant states and aging (normal and AD-associated).

PI_NAMEs: JAYKUMAR, ANKITA BACHHAWAT (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: 3xTg-AD mouse;Address;age related;Age-associated memory impairment;age-related disease;Aging;aging brain;Alzheimer's Disease;Animal Model;Area;Behavior;Behavioral;Biochemistry;Biology;Brain;career;Cells;Cellular biology;Chronic;Cognition;Cognitive;cognitive function;cognitive process;Complement;Core Facility;Data;Dementia;Deterioration;Development;Disease;Down-Regulation;Environment;Exhibits;Female;Functional disorder;Glucose;glucose metabolism;Glucose Transporter;glucose uptake;GLUT 4 protein;Goals;Hippocampus;Impaired cognition;Impairment;inhibitor;Institution;Insulin;Insulin Resistance;insulin signaling;Insulin Signaling Pathway;Lysine;male;Mediating;Mediator;Memory;memory process;Mentors;Metabolic;Metabolic dysfunction;Metabolic syndrome;Metabolism;Modeling;Molecular;Molecular Biology;Morbidity - disease rate;mortality;mouse model;Mus;neurobehavioral;Neurons;neuropathology;neurophysiology;neuropsychiatric symptom;Neurosciences;Oxidative Stress;Pathogenesis;Pharmacology;Phase;Phosphorylation;Phosphotransferases;Physiological;Physiology;Positioning Attribute;Process;Protein Kinase;Proto-Oncogene Proteins c-akt;Research;Risk Factors;Role;sex;sexual dimorphism;Signal Pathway;Signal Transduction;skills;small hairpin RNA;sortilin;Synapses;Testing;trafficking;Training;Transgenic Organisms;Vesicle;Work

PROJECT_TITLE: WNK1/OSR1 axis in Hippocampal Insulin Signaling, Glucose Metabolism and Age-related Cognitive Dysfunction

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development Facilitating The Transition to Independence Study Section[AGCD-1]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Drug Abuse (NIDA only);Eye Disease and Disorders of Vision;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Substance Misuse

ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

PHR: PUBLIC HEALTH RELEVANCE: The last 20 years of cognitive neuroscience has revealed the  functional architecture of the human brain with an exquisite degree of detail yet has left wide-open the  question of what guides the precise development, organization, and structure of the human mind. This  proposal outlines a plan to unify developmental cognitive neuroscience and computational cognitive  neuroscience to uncover the starting state of the human visual system and how it develops. The  proposed research stands to not only inform and refine theories of cortical development and inform our  understanding of neurodevelopmental differences, but also has the potential to begin to unravel one of  the most intriguing questions available to humanity: what are the origins of the human mind?

PI_NAMEs: KOSAKOWSKI, HEATHER LYNNE (contact)

PROGRAM_OFFICER_NAME: FEDOTA, JOHN RAPHAEL

PROJECT_TERMS: Adult;Architecture;Area;artificial neural network;awake;Brain;Categories;cognitive neuroscience;computational neuroscience;Computer Models;computing resources;Corpus striatum structure;Data;design;Development;Environment;experience;extrastriate;extrastriate visual cortex;Face;Functional Magnetic Resonance Imaging;fusiform face area;Goals;Human;Humanities;Infant;innovation;insight;Institution;Language;Left;Machine Learning;Magnetic Resonance;Magnetic Resonance Imaging;Maps;Mentorship;Methods;Midbrain structure;Mind;model design;Neural Network Simulation;Neurosciences;Pattern;Phase;post-doctoral training;pre-doctoral;programs;public health relevance;Research;Research Personnel;response;Stimulus;Structure;Techniques;Temporal Lobe;Testing;theories;Training;Visual System;Work

PROJECT_TITLE: Precision Mapping of Midbrain and Striatum Networks


ED_INST_TYPE: SCHOOLS OF NURSING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cardiovascular;Cerebrovascular;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Hypertension;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

PHR: PROJECT NARRATIVE Mid-life cardiovascular risk factors contribute to the development of Alzheimer’s disease in later life and to Alzheimer’s disease progression. This study will examine the relationship between cardiovascular risk factors and Alzheimer’s disease biomarkers and cognitive function in middle-aged adults with heart failure with preserved ejection fraction. Findings from this study will lead to the identification of pathways that could potentially be modified by interventions with the goal of decreasing AD risk in this high morbidity population.

PI_NAMEs: BUTTS, BRITTANY  (contact)

PROGRAM_OFFICER_NAME: FRANKOWSKI, DAVID WITT

PROJECT_TERMS: abeta accumulation;ACE2;Adult;African American;Age;Age Years;aging related disease;Alzheimer's Disease;Alzheimer's Disease Pathway;Alzheimer's disease patient;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid beta-Protein;arterial stiffness;Biological Markers;Black race;Blood;Blood - brain barrier anatomy;Blood capillaries;Blood Vessels;blood-brain barrier disruption;C-reactive protein;Cardiac;Cardiac Output;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;career development;CCL2 gene;cerebral hypoperfusion;Cerebrospinal Fluid;Cerebrovascular Circulation;clinical trial implementation;cognitive function;cohort;cytokine;Data;Development;Diagnosis;Disease Progression;EFRAC;endothelial dysfunction;Enrollment;enzyme activity;Essential Hypertension;experience;Functional disorder;Future;Goals;Health Disparities Research;health disparity;Heart failure;Hematological Disease;High Prevalence;high risk;high risk population;hyperphosphorylated tau;Hypertension;improved;Individual;Inflammation;Inflammatory;Interleukin-1 beta;Interleukin-6;Interleukin-9;Intervention;K-Series Research Career Programs;Knowledge;late life;Lead;Left Ventricular Ejection Fraction;Left Ventricular Hypertrophy;Light;Link;Longitudinal Studies;Measures;Memory;middle age;Morbidity - disease rate;mortality;neurofibrillary tangle formation;neurofilament;Not Hispanic or Latino;novel;older adult;Participant;Pathogenesis;Pathologic;Pathway interactions;Peptidyl-Dipeptidase A;Pericytes;Persons;Physiologic pulse;Platelet-Derived Growth Factor beta Receptor;Play;Population;predictive marker;preservation;Prevalence;Race;racial difference;racial diversity;Relative Risks;Renin-Angiotensin System;Research;Risk;Risk Reduction;Role;Sampling;Science;Senile Plaques;tau Proteins;tau-1;Testing;Time;TNF gene;Training;Transforming Growth Factors;translational research program;Vascular Diseases;vascular risk factor;Visuospatial

PROJECT_TITLE: Midlife Vascular Risk Factors for Alzheimer's Disease in Persons with HFpEF

STUDY_SECTION_NAME: Career Development for Clinicians/Health Professionals Study Section [AGCD-3]


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

ORG_NAME: BROAD INSTITUTE, INC.

PHR: PROJECT NARRATIVE This proposed research is relevant to public health because the discovery of the link between amyloid precursor protein trafficking defects and Alzheimer’s disease (AD) is ultimately expected to enhance understanding of AD pathogenesis as well as development of prevention and treatment. Thus, this proposed research is relevant to the part of NIH’s mission that pertains to developing fundamental knowledge that will help to reduce the burdens of human disease.

PI_NAMEs: PENG, CHUNTE  (contact)

PROGRAM_OFFICER_NAME: YANG, AUSTIN JYAN-YU

PROJECT_TERMS: Aging;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease patient;Amyloid beta-Protein Precursor;amyloid imaging;amyloid peptide;amyloid precursor protein processing;Axon;Axonal Transport;beta-site APP cleaving enzyme 1;Biochemistry;Biological Models;Blinking;career;Cell membrane;Cells;Chemistry;Color;Data;Defect;Deposition;Destinations;Development;disease model;Disease Progression;Dyes;emission line;Enzymes;fluorophore;Future;Gene Proteins;Goals;healthcare burden;Hour;Human;human disease;human embryonic stem cell;Image;Imaging Techniques;Impairment;Individual;Induced Neurons;induced pluripotent stem cell;innovation;insight;Investigation;Ions;Kinesin;Knowledge;Lead;Light;Link;luminescence;Measures;Mentors;meter;Methods;millisecond;Mission;Molecular;molecular imaging;Motor;mouse model;Mus;mutant;Mutation;nanometer;nanoparticle;Nanotechnology;Neuroglia;Neurons;next generation;novel;Optics;overexpression;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Photobleaching;physical science;Planet Earth;prevent;Prevention;Production;Property;protein transport;Proteins;Public Health;Quantum Dots;receptor;Research;Resolution;Signal Transduction;single molecule;Site;skills;spatiotemporal;stem cell technology;System;Techniques;Testing;Therapeutic;Time;trafficking;Training;Transgenic Mice;United States;United States National Institutes of Health;Vesicle;Visualization;Work

PROJECT_TITLE: Ultralong-term single-molecule imaging of amyloid precursor protein (APP) processing in Alzheimer's disease

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Project Narrative  There are few effective therapeutic options for metastatic lung adenocarcinomas (LUADs) that lack actionable  mutations  in  receptor  tyrosine  kinases,  and  there  is  an  urgent  need  to  develop  a  better  understanding  of  the  biological  basis  of  LUAD  growth  and  metastasis.  On  the  basis  of  the  preliminary  results  presented  here,  I  postulate  that  LUAD  growth  and  metastasis  is  driven  by  a  secretory  program  activated  by  epithelial- to-  mesenchymal transition (EMT). If proven true, these findings would show that EMT promotes metastasis through  a cell non- autonomous mechanism, which would advance our understanding of the molecular underpinnings of  LUAD  progression  and  would  provide  a  rationale  to  identify  actionable  targets  in  the  EMT- activated  secretory  program.

PI_NAMEs: XIAO, GUAN-YU  (contact)

PROGRAM_OFFICER_NAME: BENAVIDEZ, JUSTIN MICHAEL

PROJECT_TERMS: Achievement;Actins;actionable mutation;activating transcription factor;Adenocarcinoma Cell;Aerosols;Alleles;anti-cancer research;Apical;Award;Belief;Biogenesis;Biological;Cancer Biology;cancer cell;Cancer Center;Cancer Etiology;career development;cell fixing;Cell Line;Cell membrane;cell motility;Cell Survival;Cells;Cellular biology;Clinical;cohort;congenic;cytokine;Cytoskeleton;Data;design;Discipline;Endocytic Vesicle;Endosomes;epithelial to mesenchymal transition;Exocytosis;Focal Adhesions;Genetic Transcription;Growth;Guanosine Triphosphate Phosphohydrolases;Hot Spot;Human;human model;imaging study;Immunocompetent;inhibitor;Invaded;Kinetics;Knowledge;KRASG12D;Laboratories;Lentivirus;loss of function;Lung Adenocarcinoma;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;Medical center;Mentors;MicroRNAs;Microtubules;migration;Molds;Molecular;Monomeric GTP-Binding Proteins;Motility;mouse model;Mus;Neoplasm Metastasis;New Mexico;Organelles;Paper;Pathway interactions;paxillin;Peer Review;Physicians;Positioning Attribute;post-doctoral training;Process;Productivity;programs;Property;Protein Secretion;Proteins;Proxy;rab GTP-Binding Proteins;Receptor Protein-Tyrosine Kinases;Research;Research Personnel;Rest;Scientist;Secretory Vesicles;Signal Transduction;Site;skills;small hairpin RNA;Source;Stains;Structure;Survival Rate;targeted cancer therapy;Testing;The Cancer Genome Atlas;therapeutically effective;Tissues;trafficking;Training;Training Programs;transcriptome;Translating;tumor;tumor microenvironment;Tumor Promotion;tumor-immune system interactions;tumorigenic;Universities;Vesicle;vesicle transport;Vimentin;Work

PROJECT_TITLE: A pro-metastatic secretory program activated by epithelial-to-mesenchymal transition

STUDY_SECTION: NCI

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


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

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Diffuse glioma evolves via the interplay of mutations, DNA methylation changes, and altered gene expression, often resulting in a more aggressive and treatment-resistant form of the disease. This research proposal seeks to dissect the mechanism of glioma evolution and progression through stages of severity. Understanding the mechanism of glioma evolution can both provide targets to halt it, thereby paving the way for improved therapies and treatment timing.

PI_NAMEs: SILVERBUSH, DANA  (contact)

PROGRAM_OFFICER_NAME: MILLER, DAVID J

PROJECT_TERMS: accurate diagnosis;Address;Affect;aggressive therapy;anti-cancer research;Automobile Driving;Bar Codes;Biological Assay;Cancer Biology;cancer cell;cancer therapy;career;career development;Catalogs;Cells;Chemotherapy-Oncologic Procedure;Classification;Clinic;Clinical;clinical care;Clinical Data;Clinical Trials;Communities;Data;design;Detection;Development Plans;Diagnosis;diagnostic biomarker;diagnostic tool;Diffuse;Dimensions;Disease;Disease Progression;DNA;DNA Methylation;DNA Sequence Alteration;Doctor of Philosophy;driver mutation;effective therapy;Environment;epigenetic marker;Epigenetic Process;epigenome;Event;Evolution;Gene Expression;Gene Expression Profile;Gene Targeting;Genetic;genetic makeup;Genetic study;Genetic Transcription;Genome;genome-wide;Genotype;Glioblastoma;Glioma;Goals;Growth;Heritability;High-dimensional Modeling;improved;Individual;innovation;insight;Knowledge;Link;longitudinal dataset;Malignant neoplasm of brain;Malignant Neoplasms;Measurement;Measures;Mentorship;Methods;Methylation;Microsatellite Repeats;Modeling;multiple data types;multiple omics;mutant;Mutation;novel;Patient Care;Patients;Pattern;personalized chemotherapy;Postdoctoral Fellow;Process;Production;Protocols documentation;Records;Recurrence;Research;Research Personnel;Research Proposals;Resistance;RNA;Sampling;Scientist;Severities;single cell sequencing;single cell technology;single-cell RNA sequencing;Somatic Mutation;Structure;System;targeted treatment;Technology;Testing;therapeutic target;Time;tool;Training;transcriptome;transcriptomics;Treatment Efficacy;treatment response;tumor;tumor DNA;tumor progression;Tumor stage;Work

PROJECT_TITLE: Decoding glioma evolution and progression by multi-dimensional single-cell profiling


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

ORG_STATE: WA

PHR: Project Narrative Acute myeloid leukemia (AML) remains a devastating illness, with a clear need for the development of novel anti-leukemic therapy. This proposal will characterize the molecular mechanism of MARCH5 protein and its interactome in regulating apoptosis, and evaluate the translational potential of MARCH5 inhibition as an AML therapy and a synergistic approach to enhance the efficacy of venetoclax. This study will reveal novel insights of apoptosis regulation in AML, and provide biological basis for the development of strategies targeting MARCH5 to benefit patients with AML.

PI_NAMEs: LIN, SHAN  (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Acute leukemia;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Advisory Committees;Apoptosis;Apoptosis Regulation Gene;Apoptotic;Award;BCL2 gene;BCL2L1 gene;Biochemical;Biological;cancer cell;cancer survival;career;Cell Death;cell growth;Cell Physiology;Clinic;Clinical;clinical application;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;collaborative environment;Communities;CRISPR screen;CRISPR/Cas technology;Critical Thinking;Dana-Farber Cancer Institute;Data;Dependence;Development;Dropout;Enzymes;Essential Genes;Exhibits;Family member;frontier;functional genomics;Genetic;genetic regulatory protein;Goals;Growth;Hematologic Neoplasms;human model;improved;In Vitro;in vivo;inhibitor;insight;Intervention;Knock-out;Knowledge;Laboratories;leukemia;leukemia treatment;leukemogenesis;Maintenance;Malignant Neoplasms;MCL1 gene;MDM2 gene;Mediating;Mentorship;Mitochondria;Molecular;multicatalytic endopeptidase complex;novel;novel therapeutic intervention;novel therapeutics;older adult;Oncogenic;patient subsets;Patients;pediatric department;Pediatric Oncology;Pharmaceutical Preparations;pharmacologic;Postdoctoral Fellow;Pre-Clinical Model;prevent;Prognosis;programs;Protein Family;Proteins;Regulation;Research;Resistance;Resistance development;Resources;Role;skills;Solid;Specificity;Stress;Substrate Interaction;System;targeted cancer therapy;targeted treatment;Technical Expertise;Therapeutic;therapeutic development;therapeutic target;Training;Translating;translational potential;tumor;Ubiquitin;Ubiquitin-Activating Enzymes;Ubiquitin-Conjugating Enzymes;ubiquitin-protein ligase;Ubiquitination;Vision;Xenograft Model

PROJECT_TITLE: Characterizing the role of MARCH5 in apoptosis regulation in acute myeloid leukemia


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

ORG_DEPT: GENETICS

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: Project narrative: Cdh1 is a well-established tumor suppressor by targeting various oncogenic substrates for proteasomal degradation. However, the molecular mechanisms by which the E3 ligase activity of Cdh1 is regulated remains largely elusive. The major goal of this proposal is to explore mechanistically how the upstream regulator, CDK4, suppresses the E3 ligase activity of Cdh1 by mediating its phosphorylation, as well as to uncover a novel role of the APC/CCdh1 ubiquitin E3 ligase complex in retarding breast tumorigenesis by targeting the PIN1 oncoprotein, for poly-ubiquitination and degradation.

PI_NAMEs: DANG, FABIN  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Adaptor Signaling Protein;Anaphase;anaphase-promoting complex;Breast Cancer Cell;Breast Cancer therapy;breast tumorigenesis;cancer stem cell;cancer therapy;CDK4 gene;Cell Culture Techniques;Cell Cycle;Cell Cycle Arrest;Cell Cycle Progression;Cell Cycle Proteins;Cell Cycle Regulation;Cell Maintenance;Cell Proliferation;Cells;Clinical;Complex;Couples;Cyclin D1;Data;design;Development;Employment;Exhibits;G1 Phase;Genetic;Goals;Human;Immune System Diseases;In Vitro;in vivo;inhibitor;kinase inhibitor;Maintenance;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Metaphase;Mitosis;Modeling;Molecular;mouse genetics;multicatalytic endopeptidase complex;Mutate;novel;novel therapeutics;Oncogenic;Oncoproteins;overexpression;Pathway interactions;Peptidylprolyl Isomerase;Phosphorylation;Phosphorylation Site;Phosphotransferases;Physiological;Pin1 protein;Play;Polyubiquitination;prevent;Process;protein degradation;protein expression;protein function;Proteins;RB1 gene;Regulation;response;Role;S phase;Serine;Signal Transduction;synergism;Therapeutic;Therapeutic Effect;Threonine;Tumor Suppressor Proteins;tumorigenesis;Ubiquitin;ubiquitin-protein ligase;Work

PROJECT_TITLE: Novel regulation of the CDK4/Cdh1/Pin1 signaling axis for targeted breast cancer therapies


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: BRONX

ORG_NAME: JAMES J PETERS VA  MEDICAL CENTER

PHR: Dialectical Behavior Therapy for Justice-Involved Veterans (DBT-J) is a comprehensive, integrative program distinctively designed to address the range of mental health, substance use, case management, and legal needs of Veterans with current or ongoing criminal justice involvement. Data from two prior clinical trials attest to the program’s feasibility and acceptability and preliminarily suggest participation in the program may yield meaningful improvements in risk for criminal behavior and resolution of high-priority case management needs. However, continued research is needed to further investigate the program’s efficacy. The proposed Phase III clinical trial aims to investigate the superiority of DBT-J over a supportive group therapy treatment in decreasing risk of future criminal behavior and increasing psychosocial functioning. Secondary and exploratory aims will also investigate superiority of DBT-J in improving secondary treatment targets, potential differential efficacy across special-interest Veteran subgroups, and long-term consequences of program participation.

PI_NAMEs: EDWARDS, EMILY R (contact)

PROJECT_TERMS: acceptability and feasibility;Address;Alternative Therapies;antisocial behavior;Behavior;behavioral health;Caring;Case Management;Classification;Clinical;Clinical Trials;Communities;criminal behavior;Criminal Justice;Data;design;Diagnostic;Dialectical behavior therapy;disability;Disadvantaged;distrust;Elements;Eligibility Determination;evidence base;experience;Feeling suicidal;follow-up;Future;Group Psychotherapy;Group Therapy;high risk;housing instability;improved;interest;Intervention;Interview;Investments;Justice;Legal;Life;Measurement;Measures;Medical;Mental Health;military veteran;Mission;Modeling;mortality risk;Outpatients;Participant;Patient Self-Report;peer;Phase III Clinical Trials;Population;Principal Investigator;Process;programs;psychological distress;psychosocial;Quality of life;Randomized;randomized, clinical trials;recidivism;Recording of previous events;Rehabilitation therapy;Research;resilience;Resolution;Resources;Risk;Risk Assessment;Risk Factors;Role;Services;severe mental illness;Social Environment;social stigma;Structure;Subgroup;substance use;Substance Use Disorder;substance use treatment;suicidal morbidity;suicidal risk;Suicide;Suicide prevention;suicide rate;supported housing;Survivors;System;Thinking;Trauma;Treatment Efficacy;Underemployment;United States Department of Veterans Affairs;Veterans;Veterans Health Administration;Violence

PROJECT_TITLE: Dialectical Behavior Therapy for Justice-Involved Veterans: A Randomized Clinical Trial

STUDY_SECTION_NAME: Behavioral Health & Social Reintegration[RRD4]


FUNDING_MECHANISM: OTHERS

ORG_CITY: BEDFORD

ORG_NAME: EDITH NOURSE  ROGERS MEMORIAL VETERANS HOSPITAL

PHR: 1 Health-related adverse events are unacceptably high among Veterans receiving VA-funded home care,  2 particularly home care patients with both dementia and other chronic conditions. This Career Development  3 Award extends VA’s patient safety initiative into a novel care setting that serves high-risk Veterans. My  4 study will estimate potentially avoidable hospitalization rates and identify home care processes family  5 caregivers & home care agency workers use to recognize and manage early warning signs of adverse  6 events. It will also adapt, pilot, and refine a tool to help family caregivers & home care agency workers  7 recognize early warning signs. My background in gerontology and skills in VA data use and qualitative  8 methods partially prepare me for this work. My proposal fills training gaps— in non-VA data sources and  9 advanced statistical methods for causal inference, mixed methods, care coordination, and user-centered 10 design—and provides VA with rigorous, actionable research by which to improve patient safety.

PI_NAMEs: QUACH, EMMA  (contact)

PROJECT_TERMS: abuse neglect;Address;Adopted;Adverse event;adverse event risk;adverse outcome;Aging;Attention;authority;Award;care coordination;career;career development;Caregivers;Caring;Characteristics;Chronic;Clinic;Clinical;cohort;Communities;Complex;cost;Data;Data Sources;Databases;Dehydration;Dementia;design;Detection;Early Diagnosis;Effectiveness;effectiveness testing;Environment;Event;experience;fall injury;Family Caregiver;Family Process;family support;Frontline worker;Funding;Future;Geriatrics;Gerontology;Growth;Health;Health Care Costs;health care delivery;Health care facility;health equity;high risk;Home;Home Care Agencies;Homogeneously Staining Region;Hospitalization;hospitalization rates;Hospitals;hybrid type 1 design;hybrid type 1 study;implementation tool;improved;Infection;Injury;innovation;Interview;Knowledge;Literature;Long-Term Care;Medical;medical complication;medical specialties;Medicare;member;Mentors;Mentorship;Methods;Neighborhoods;novel;Nursing Homes;Outcome;Patient Care;patient home care;patient safety;Patients;Personal Satisfaction;Policies;Population;Prevalence;prevent;Prevention;Primary Care;primary care team;Process;process improvement;Provider;Qualitative Methods;Research;Resources;Risk;Role;Safety;skills;Statistical Methods;study population;Survey Methodology;Surveys;theories;tool;Training;user centered design;Veterans;Work

PROJECT_TITLE: Applying high-reliability organization principles to home care to enhance patient safety

STUDY_SECTION_NAME: Research Career Scientist[MRA0]


ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

PHR: Transforming specialty care for pulmonary hypertension (PH) across VA into a telehealth-enhanced hub-and- spoke model is an evidence-based, guideline-recommended solution to address current gaps in the access, quality, and equity of PH care for the more than 250,000 Veterans living with this devastating disease. Yet, before VA can undertake organizational redesign efforts, a formative evaluation is required to ensure that these efforts will meet Veteran needs and improve Veteran outcomes. Within this study, we will leverage mixed methods data including survey data and qualitative interviews to characterize stakeholder perspectives on PH care within potential hub sites. We will then partner with stakeholders to co-design an implementation blueprint, which will use to pilot test the telehealth-enhanced hub-and-spoke model across two VISN 1 sites to assess the feasibility and acceptability of the model. The results of this work will inform the scaling of the model across all VISN 1 sites in the next phase to assess its impact on clinical outcomes.

PI_NAMEs: GILLMEYER, KARI  (contact)

PROJECT_TERMS: acceptability and feasibility;Address;Affect;authority;Boston;care coordination;care delivery;care delivery site;care fragmentation;career;career development;Caring;Characteristics;chronic care model;Clinic;Clinical;Clinical Decision Support Systems;Communities;Complex;Consult;cost outcomes;Data;Data Collection;design;Disease;effectiveness evaluation;effectiveness/implementation hybrid;Electronics;Ensure;Epilepsy;Equity;Evaluation;evidence base;experience;Face;formative assessment;Future;gaps in access;Goals;Guidelines;Health;Health Services;Health Services Accessibility;Health Services Research;Health Technology;Healthcare Systems;implementation design;implementation questions;implementation science;implementation strategy;Improve Access;improved;improved outcome;Information Systems;innovation;Interview;iterative design;Knowledge;Lead;Leadership;Learning;Maine;Mediating;medical specialties;Mentorship;Methodology;Methods;military veteran;Modeling;mortality;multidisciplinary;Outcome;Patients;Phase;pilot test;pilot trial;Positioning Attribute;Process;Productivity;programs;Provider;Pulmonary Hypertension;Pulmonology;Quality of Care;Recommendation;recruit;Reporting;Research;Research Methodology;Research Personnel;Rural;Rural Health;Series;Services;Site;Specific qualifier value;stakeholder perspectives;standardized care;Surveys;System;Technology;telehealth;telestroke;theories;tool;Training;Variant;Veterans;virtual;virtual visit;Work

PROJECT_TITLE: Veteran-Centered Transformation of Pulmonary Hypertension Organization into a Regional Model of Care in VA (TRANSPHORM-VA)


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Immunotherapy

ORG_CITY: CORAL GABLES

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Past work in IL-2R signaling in mice have led to a new promising therapeutic strategy, i.e. low-dose IL-2, for the treatment of autoimmune diseases. The current study will provide a much more mechanistic underpinning concerning the contribution of IL-2R signaling in shaping the peripheral Treg compartment that cannot be readily defined in humans. Results from this work has the potential to identify new pathways and processes that may be targeted to refine IL-2-based immunotherapy for autoimmunity or that may represent a risk for autoimmune diseases.

PI_NAMEs: MALEK, THOMAS R (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: Acceleration;Address;Alpha Interleukin 2 Receptor;Apoptosis;Apoptotic;Autoimmune;Autoimmune Diseases;Autoimmunity;BCL2 gene;cancer immunotherapy;Cell Compartmentation;Cell Maturation;Cell Physiology;Cellular Metabolic Process;cholesterol biosynthesis;clinical translation;conditional knockout;cytokine;Data;Development;Diabetes Mellitus;Dose;FOXP3 gene;genetic signature;genome-wide;Homeostasis;Human;IL2RA gene;Immune;immune checkpoint blockade;Immunotherapy;Impairment;Inbred NOD Mice;Interleukin-2;Islets of Langerhans;Knockout Mice;life span;Link;lipid biosynthesis;man;Mediating;Metabolic;Modeling;Molecular;mouse model;Mus;novel;Overlapping Genes;Pathway interactions;Peripheral;Predisposition;Process;Regulation;Regulatory T-Lymphocyte;response;Rest;Risk;Role;Shapes;side effect;Signal Induction;Signal Transduction;Stat5 protein;System;T-Lymphocyte Subsets;targeted treatment;Therapeutic;Thymus Gland;Translations;Work

PROJECT_TITLE: IL-2R-dependent mechanisms in regulation of Treg homeostasis and autoimmunity

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_CITY: DURHAM

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Cells in the trabecular meshwork are constantly subjected to mechanical forces and deformations resulting from changes in intraocular pressure and eye movement; it is expected trabecular meshwork cells to possess adaptive mechanisms, which allow them to cope to this stress and prevent further injury. The objective of this grant proposal is to investigate the mechanisms by which autophagy, a cellular survival pathway, is activated and regulate a stretch-induced healing response. Pharmacological modulation of this cellular pathway can constitute a novel therapeutic strategy for glaucoma.

PI_NAMEs: LITON, PALOMA  (contact)

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: Actins;Aging;Anterior;Anterior eyeball segment structure;Applications Grants;Aqueous Humor;Area;Autophagocytosis;Binding;Cell Nucleolus;Cells;Cilia;cilium biogenesis;Circadian Rhythms;Collagen;coping;Couples;cytokine;Cytoskeleton;Data;Drainage procedure;Endothelium;experimental study;Extracellular Matrix;Eye;Eye Movements;Family suidae;fluid flow;Functional disorder;Gene Expression;Glaucoma;Goals;healing;Homeostasis;Human;Injury;innovation;Laboratories;Length;Loose connective tissue;MADH2 gene;mechanical force;Mechanical Stress;Mechanics;mechanotransduction;mouse model;Nature;new therapeutic target;novel;novel therapeutic intervention;Nuclear;Nuclear Translocation;Ocular Hypertension;Pathologic;Pathway interactions;Perfusion;pharmacologic;Physiologic Intraocular Pressure;Physiologic pulse;Physiological;Physiology;Play;pressure;Prevalence;prevent;Proteomics;proteostasis;Proto-Oncogene Proteins c-akt;Regulation;Relaxation;repaired;Reporting;response;Risk Factors;Role;Signal Pathway;Signal Transduction;Stress;Stretching;Testing;Time;Tissues;Trabecular meshwork structure;Transforming Growth Factor beta;Transgenic Mice;Translating;Variant

PROJECT_TITLE: Autophagy and Mechanotransduction in the Trabecular Meshwork

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


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: American Indian or Alaska Native;Basic Behavioral and Social Science;Behavioral and Social Science;Childhood Obesity;Clinical Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Pediatric;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NORTH ANDOVER

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: MERRIMACK COLLEGE

PHR: PROJECT NARRATIVE Schools are increasingly recognized as a priority area for obesity prevention efforts, particularly among children with socioeconomic disadvantage and/or who are racial/ethnic minorities, and strong policies related to school meals and physical activity are considered key strategies. Two promising, cost-effective policies are longer lunch periods and longer recess with integrated physical activity opportunities throughout the day, but rigorous evidence is lacking. In this time-sensitive study, we will evaluate the effects of a wellness initiative targeting these policies in Anchorage Alaska, and measure the impact on students’ school meal consumption and physical activity levels, as well as weight status, sleep duration/quality, and other factors related to academic performance.

PI_NAMEs: COHEN, JULIANA FW (contact)

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TERMS: Academy;Accelerometer;Address;Adoption;Alaska;Alaska Native;Alaska Native population;American Indian Population;American Indians;Area;Behavior;Behavioral;Body mass index;Child;Child Health;Consumption;cost effective;Data;Data Collection;Development;Diet;dietary;Dietary intake;Disparity;Effectiveness;elementary school;Energy Intake;Ensure;ethnic diversity;ethnic minority;Evaluation;evidence base;experience;Family;federal policy;follow-up;fourth grade;Fruit;Funding;Habits;Health;health disparity;Healthy Eating;Human Resources;Hunger;implementation fidelity;improved;innovation;Instruction;Knowledge;Length;Light;Location;Low income;Measurement;Measures;Medicine;Methodology;Milk;Minority Groups;moderate-to-vigorous physical activity;Movement;Natural experiment;nutrition;Obesity;obesity in children;obesity prevention;obesity risk;Outcome;Outcome Assessment;Performance;Physical activity;Policies;Policy Maker;post implementation;Public Health;racial diversity;racial minority;Recommendation;Research;Research Design;Risk;Risk Factors;Risk Reduction;Scanning;school district;School Nursing;Schools;sedentary;Site Visit;Sleep;socioeconomic disadvantage;socioeconomics;Specialist;Standardization;Strenuous Exercise;student participation;Students;Surveys;teacher;Testing;Time;Unhealthy Diet;Vegetables;Visit;wasting;Weight;Work

PROJECT_TITLE: Evaluation of a District-Wide Initiative to Improve School Meal Consumption and Physical Activity Levels among Elementary Students in Anchorage, Alaska


NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Cerebral Palsy;Childhood Injury;Disability Research;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Physical Injury - Accidents and Adverse Effects;Precision Medicine;Preterm, Low Birth Weight and Health of the Newborn;Unintentional Childhood Injury

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative: Public Health Relevance Section Lack of oxygen to the newborn brain is the major cause of lifelong disability in children resulting in mental retardation, epilepsy and cerebral palsy. Understanding pathways for protecting the brain will result in therapeutic avenues for brain recovery.

PI_NAMEs: FERRIERO, DONNA M. (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Biochemical;Biological Assay;Brain;Brain Injuries;Carbon;Cause of Death;Cell Compartmentation;Cerebral Palsy;Cerebrum;Child;ChIP-seq;Clinic;Clinical Research;CRISPR/Cas technology;disability;Epilepsy;Evolution;excitotoxicity;Genetic;Human;Hypoxia Inducible Factor;Imaging Techniques;improved outcome;In Vitro;in vivo;Individual;individualized medicine;Inflammation;Injury;innovation;Lifelong disability;Link;Magnetic Resonance Spectroscopy;Mental Retardation;Metabolic;metabolic imaging;Molecular;molecular targeted therapies;Mus;natural hypothermia;Neonatal Brain Injury;neonatal hypoxic-ischemic brain injury;neurovascular;Newborn Infant;Non-Invasive Detection;novel;oxidant stress;Oxygen;Pathway interactions;Patients;Phase;postnatal;Precision therapeutics;protective pathway;Protons;public health relevance;Recovery;Regulation;repaired;responders and non-responders;response;response to injury;Signal Pathway;Signal Transduction;Spectrum Analysis;standard of care;Techniques;Therapeutic;therapy design;Time;tool;Translating

PROJECT_TITLE: Precision Therapy for Neonatal Brain Injury


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Behavioral and Social Science;Brain Disorders;Clinical Research;Genetics;HIV/AIDS;Infectious Diseases;Machine Learning and Artificial Intelligence;Mental Health;Microbiome;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Cognitive and mood disorders occur more commonly in people with HIV than in the general population but the field still does not fully understand why and has no effective therapies for most of those who are affected. This project will take a new approach to understanding how cognition, mood, substance use, and medical characteristics cluster together and will identify new biological mechanisms associated with these conditions. The successful project could lead to new diagnostic tests and therapies for these disorders, which would have substantial public health relevance.

PI_NAMEs: ELLIS, RONALD J.;LETENDRE, SCOTT L (contact)

PROGRAM_OFFICER_NAME: RAO, VASUDEV RAMACHANDRA

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Affect;AIDS dementia;antiretroviral therapy;Biological;Biological Assay;Biological Markers;Biology;biopsychosocial;Blood;Brain imaging;Categories;Central Nervous System;Central Nervous System Diseases;Cerebrospinal Fluid;Characteristics;Classification;Clinical;Cognition;Cognition Disorders;Cognitive;Cognitive deficits;Cohort Studies;comorbidity;daily functioning;Data;Diagnosis;Diagnostic tests;Disease;disease classification;effective therapy;Encephalitis;Frequencies;Funding;General Population;Genetic;genome wide association study;Goals;Gut associated lymphoid tissue;gut dysbiosis;Heterogeneity;high dimensionality;HIV;HIV anti-retroviral;HIV-associated neurocognitive disorder;Image;Individual;Inflammation;Injury;innovation;Intervention;Investments;Life;Machine Learning;machine learning method;magnetic resonance spectroscopic imaging;Mediating;Medical;metabolome;Methods;microbial;microbiome;microbiome analysis;Mood Disorders;Moods;multidimensional data;neuroAIDS;neurobehavioral;Neurocognitive Deficit;neurocognitive disorder;Neuropsychological Tests;novel;novel diagnostics;novel strategies;novel therapeutics;Participant;Pathogenesis;Pathology;Performance;Persons;Pharmaceutical Preparations;Phenotype;Production;progression risk;Proteins;public health relevance;Research;Research Priority;Risk Factors;RNA;sex;Sex Differences;Site;Specimen;Standardization;substance use;supervised learning;United States National Institutes of Health;unsupervised learning;Work

PROJECT_TITLE: Biopsychosocial Phenotypes and Potential Mechanisms in CHARTER

STUDY_SECTION: HCCS

STUDY_SECTION_NAME: HIV Comorbidities and Clinical Studies Study Section[HCCS]


NIH_SPENDING_CATS: Biotechnology;Complementary and Integrative Health;Dietary Supplements;Digestive Diseases;Immunization;Infectious Diseases;Microbiome;Nutrition;Pediatric;Prevention;Vaccine Related

ORG_CITY: FORT COLLINS

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: PROJECT NARRATIVE Rotavirus continues to be a leading cause of diarrheal disease and death in children under 5 years of age. Currently licensed vaccines are 35-40% less effective in underdeveloped regions as compared to developed countries. We have developed an orally-delivered vaccine based on the probiotic organism, Lactobacillus acidophilus. We will use state-of-the-art technology to construct a sophisticated, novel vaccine that will address safety concerns and efficacy gaps that exist will current vaccines.

PI_NAMEs: ABDO, ZAID ;BARRANGOU, RODOLPHE ;DEAN, GREGG A (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: 5 year old;Address;Adjuvant;Affect;Age;Agonist;Animals;Antibiotic Resistance;Antibody Response;Antigens;Attenuated;Attenuated Vaccines;Biological Assay;Capsid;Capsid Proteins;Cause of Death;Cells;Cessation of life;Child;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Cold Chains;comparative efficacy;Country;CRISPR/Cas technology;Data;Developed Countries;Developing Countries;Development;diarrheal disease;Disease;Engineering;enteric pathogen;Epitopes;Family suidae;fecal microbiome;Flagellin;gastrointestinal;Genetic Transcription;Genome;Gnotobiotic;Hospitalization;Human;immune activation;Immune response;Immunization;Immunize;immunogenic;immunogenicity;Immunoglobulin A;Inbred BALB C Mice;Individual;Infant;Injections;innovation;interest;Intussusception;Knowledge;Lactobacillus acidophilus;Length;Licensing;Licensure;M cell;microbiome;microorganism;Modeling;Morbidity - disease rate;mortality;mouse model;Mucosal Immune Responses;mucosal vaccine;Mucous Membrane;Mus;neutralizing antibody;next generation;novel;novel vaccines;Oral;oral vaccine;Organism;Pathogenicity;Peptides;Populations at Risk;porcine model;Probiotics;programs;Proteins;Recombinants;Recommendation;resistance gene;Risk;Rotavirus;Rotavirus disease;Rotavirus Infections;Rotavirus Vaccines;Safety;Subunit Vaccines;System;Technology;Testing;Transplantation;vaccination protocol;vaccine access;vaccine candidate;vaccine delivery;vaccine immunogenicity;vaccine platform;vaccine strategy;Vaccines;Viral;Virulence;Virus;Virus Replication;World Health Organization

PROJECT_TITLE: Novel recombinant Rotavirus vaccine utilizing the probiotic microorganism Lactobacillus acidophilus

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


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

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Adeno-associated virus (AAV) vector-mediated gene delivery has been successfully used in patients with blindness and bleeding diseases, however, early clinical trials demonstrated no improvement of lung function in CF patients treated with AAV vector mediated CFTR airway delivery perhaps due to airway physical barriers and low transduction. In this application, we will explore two novel strategies to increase AAV vector ability to cross the blood vascular barrier and enhance AAV transduction in airway epithelial cells after systemic administration for CF gene therapy. The results generated from these studies will allow us to develop an effective approach to treat CF patients using AAV vector mediated gene delivery.

PI_NAMEs: LI, CHENGWEN ;SAMULSKI, RICHARD J (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Address;adeno-associated viral vector;adenovirus mediated delivery;Airway Disease;airway epithelium;Animal Model;apical membrane;autosome;basolateral membrane;Binding;Blindness;Blood;Blood Coagulation Disorders;Blood Vessels;Capsid;cellular transduction;Clinical Trials;Complication;CRISPR/Cas technology;Cystic Fibrosis;cystic fibrosis airway epithelia;cystic fibrosis mouse;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;delivery vehicle;Dependovirus;Development;Directed Molecular Evolution;Disease;DNA;ds-DNA;early phase clinical trial;Epithelial Cells;Failure;Gene Delivery;gene therapy;gene-editing approach;Genes;Genetic Diseases;Genetic Engineering;Genome;Hemorrhage;High Prevalence;Human;improved;In Vitro;Incubated;Intravenous Immunoglobulins;Libraries;Longitudinal Studies;Lung;Lung Diseases;Measurable;Mediating;Morbidity - disease rate;mortality;Mus;mutant;Mutation;neutralizing antibody;novel;novel strategies;Organ;Patients;Peptides;Peripheral;Persons;Phage Display;Phenotype;Property;Proteins;pulmonary function;recessive genetic trait;Regulator Genes;Serotyping;small molecule;success;Technology;Testing;Tissues;transduction efficiency;Transduction Gene;Variant;Vascular Permeabilities;vector;vector induced;Viral Genome;Viral Packaging;Virion

PROJECT_TITLE: Development of AAV vectors for CF therapy

STUDY_SECTION: GDD

STUDY_SECTION_NAME: Gene and Drug Delivery Systems Study Section[GDD]


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Childhood Leukemia;Clinical Research;Clinical Trials and Supportive Activities;Hematology;Orphan Drug;Patient Safety;Pediatric;Pediatric Cancer;Prevention;Rare Diseases

ORG_CITY: BUFFALO

ORG_NAME: ROSWELL PARK CANCER INSTITUTE CORP

PHR: Public Health Significance Recent landmark studies from the Children’s Oncology Group (COG) highlight adherence to home-based oral chemotherapy as an enduring problem in pediatric cancer care. Yet, little is known about why some families have difficulty adhering to their child’s home-based oral chemotherapy while others do not. Through the novel examination of how behavioral parenting skills shape adherence at the episode and daily levels the proposed program of research has potential to lead to a paradigm shift in pediatric cancer adherence risk prediction and interventions, moving away from blunt demographic-based risk prediction and identifying behavioral parenting skills that are easily amenable to screening, modifiable, and may be more precise predictors of non-adherence risk.

PI_NAMEs: BOUCHARD, ELIZABETH  (contact)

PROGRAM_OFFICER_NAME: FERRER, REBECCA

PROJECT_TERMS: Acute Lymphocytic Leukemia;Adherence;Age;Behavior assessment;behavior measurement;Behavioral;Biological Markers;biomarker validation;cancer care;Cancer Relapse;cancer risk;caregiving;Cause of Death;Cessation of life;chemotherapy;Child;Child Behavior;Child health care;Child Rearing;Childhood;Classification;clinical care;clinically significant;Code;Conflict (Psychology);Data;Data Collection;Deglutition;diaries;Disease;Dose;Drops;Drug Prescriptions;Education;Educational process of instructing;efficacy evaluation;Electronics;Enrollment;Ensure;Equation;experience;Family;Goals;Health Care Costs;health disparity;Home;Hospitalization;improved;Ingestion;innovation;Intervention;Learning;Life;Malignant Childhood Neoplasm;Malignant Neoplasms;Measurement;Measures;Medical;medication administration;medication compliance;Medication Management;medication nonadherence;Medicine;Methodology;Methods;Modeling;Monitor;Morbidity - disease rate;mortality;novel;Nurses;Oral;Parents;Participant;Patient Self-Report;Patients;Pediatric Oncology Group;Pediatrics;Pharmaceutical Preparations;pharmacologic;pill;Procedures;programs;Public Health;Randomized, Controlled Trials;recruit;Research;Resistance;restraint;retention rate;Risk;risk prediction;satisfaction;Schedule;Scheme;screening;secondary outcome;Shapes;side effect;skills;Specific qualifier value;Stress;Surveys;Techniques;Testing;Time;translational impact;treatment as usual;Treatment Failure;Treatment outcome;United States National Institutes of Health;usability

PROJECT_TITLE: Behavioral Parenting Skills as a Novel Target for Improving Pediatric Medication Adherence

STUDY_SECTION: CMGC

STUDY_SECTION_NAME: Clinical Management in General Care Settings Study Section[CMGC]


PHR: Mechanisms of labor onset in humans remain largely mysterious and this gap in knowledge has profound negative implications for human health since it precludes attempts to develop rational therapies for preterm birth, a major cause of neonatal morbidity and mortality. Here, we will dissect a novel immunological regulatory circuit active within the prepartum uterus that drives parturition in mice. These studies might open up new avenues for dissecting the mechanisms of human parturition and for determining how such mechanisms are dysregulated in disorders of human pregnancy.

PI_NAMEs: ERLEBACHER, ADRIAN  (contact)

PROGRAM_OFFICER_NAME: PRABHUDAS, MERCY R

PROJECT_TITLE: The IL-33/ILC2 axis in parturition

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Macular Degeneration;Neurodegenerative;Neurosciences;Regenerative Medicine

ORG_CITY: Albany

ORG_NAME: REGENERATIVE RESEARCH FOUNDATION

PHR: Project Narrative The retinal pigment epithelium (RPE) degenerates in diseases such as dry age-related macular degeneration (AMD), for which no therapy is currently available. Here we propose to develop a novel approach to RPE repair –increasing the number of RPE cells by stimulating their division. We will define the environmental factors regulating adult human RPE proliferation using cutting edge methods to assess protein expression. Then, we will use targeted screens to test specific genes, growth factors and small molecules for potential to repair the RPE layer.

PI_NAMEs: TEMPLE, SALLY  (contact)

PROGRAM_OFFICER_NAME: FORTRESS, ASHLEY

PROJECT_TERMS: Acute;Address;Adult;Age related macular degeneration;Bioinformatics;bioinformatics tool;Blindness;Bruch's basal membrane structure;Cadaver;Cell division;Cell membrane;Cell secretion;Cell surface;Cell Surface Receptors;Cell Survival;Cell Transplantation;Cells;Clinical Trials;CRISPR interference;Data;Disease;Elderly;Environment;Environmental Risk Factor;Epithelial Cell Proliferation;epithelial repair;Exogenous Factors;Extracellular Domain;Eye;Female;FGF2 gene;fibroblast growth factor 18;Foundations;Genes;genetic manipulation;Genetic Transcription;Glycoproteins;Goals;Growth Factor;Human;Immunosuppression;improved;In Situ;In Vitro;in vivo;induced pluripotent stem cell;innovation;interest;Interphase Cell;KITLG gene;Knowledge;Ligands;male;manufacture;Mass Spectrum Analysis;Methods;Mitogens;monolayer;Natural regeneration;Nonexudative age-related macular degeneration;novel strategies;Operative Surgical Procedures;Pathway Analysis;Pathway interactions;patient population;Patients;Photoreceptors;prevent;programs;Proliferating;protein expression;Protein Secretion;Proteins;Proteomics;receptor;repaired;Retina;Retinal Degeneration;retinal stimulation;small hairpin RNA;small molecule;Source;stem cells;Structure of retinal pigment epithelium;System;Testing;therapy development;transcriptome sequencing;Translating;Translations;Work

PROJECT_TITLE: Characterizing Human RPE Cell Proliferation to Advance Endogenous Regeneration

STUDY_SECTION: DPVS

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


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cerebrovascular;Hematology;Neurosciences;Orphan Drug;Prevention;Rare Diseases;Sickle Cell Disease

ORG_CITY: CINCINNATI

ORG_NAME: UNIVERSITY OF CINCINNATI

PHR: Project Narrative Individuals with sickle cell disease (SCD) develop cognitive and other behavioral abnormalities, which are a major source of disability, including loss of job/unemployment and economic potential. The aim of this proposal is to identify the biological factors involved in the development of these learning and behavioral abnormalities and to potentially advance our understanding of their role in the development of these complication and also whether they could be used as targets of drugs and/or prevention efforts.

PI_NAMEs: HYACINTH, HYACINTH IDU (contact)

PROGRAM_OFFICER_NAME: ZOU, SHIMIAN

PROJECT_TERMS: Address;Adult;Age;Age of Onset;aged;Agonist;Anemia;Anxiety;Behavioral;Biological Factors;Blood flow;Blood Vessels;Bone Density;Bone Marrow;Brain;Cerebral Infarction;Cerebral Ischemia;cerebral ischemic injury;cerebral microinfarct;Cerebrum;Child;Chronic;Clinical Trials;Cognitive;Cognitive deficits;cognitive function;cohort;Communication;Complication;Cross-Sectional Studies;cytokine;Dendrites;Dendritic Spines;density;design;Development;disability;Drug Targeting;Economics;Educational Status;FDA approved;Genes;Golgi Apparatus;Healthcare;Hippocampus;Histologic;Histology;Image;Immunohistochemistry;improved;in vivo;Individual;Infarction;Inflammation;Inflammatory;Injury;Intelligence quotient;Intervention;Job loss;Knowledge;Laser Scanning Microscopy;Learning;Life;Link;low socioeconomic status;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Mediating;Mediator;Memory;Mental Depression;Microglia;Minocycline;Modeling;Molecular;Morphology;Mus;neuroinflammation;Neuronal Plasticity;neuronal survival;Neurons;neurotrophic factor;Neurotrophic Tyrosine Kinase Receptor Type 2;novel therapeutic intervention;novel therapeutics;Outcome;Pathologic;Pathologic Processes;Patients;Peripheral;Pharmaceutical Preparations;Pilot Projects;pre-clinical;prevent;Prevention;Prevention strategy;prospective;PTPRC gene;Quality of life;Randomized;receptor;Reporting;Research;Research Design;Resources;Role;Severities;Sickle Cell;Sickle Cell Anemia;Signal Transduction;small molecule;Source;Stroke;systemic inflammatory response;Testing;Therapeutic;treatment strategy;two-photon;Unemployment;Vascular Diseases;Vertebral column

PROJECT_TITLE: Minocycline as a potential therapy for neuroinflammation and cognitive deficit in sickle cell disease

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: We have recently developed a novel and paradoxical approach to treat castration resistant prostate cancer patients by using supraphysiologic testosterone (SupraT) termed bipolar androgen therapy (BAT) as a therapy for this disease. The proposed work will provide mechanistic insights into how SupraT works at the molecular and cellular level. Successful completion of the project will inform us whether SupraT involves immune activation and immune editing of prostate tumors, an insight, which could transform the clinical management of patients with metastatic castration-resistant prostate cancer in the immediate term.

PI_NAMEs: DENMEADE, SAMUEL R;KACHHAP, SUSHANT KRISHNA (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Adaptive Immune System;advanced prostate cancer;Agonist;Androgen Analogues;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;Androgen Therapy;Androgens;antitumor effect;Apoptosis;Autophagocytosis;Autophagosome;biomarker development;Biopsy;Cancer Biology;cancer immunotherapy;Cancer Patient;Castration;Cell model;Cells;chemokine;Chronic;Clinical;Clinical Management;Clinical Research;CRISPR/Cas technology;Cytoplasm;Data;Defect;digital;Disease;DNA;DNA Damage;DNA Double Strand Break;DNA Repair;DNA Repair Disorder;DNA Repair Gene;Dose;ds-DNA;empowerment;Environment;exposed human population;Exposure to;FDA approved;Gene Amplification;Genes;genetic signature;Goals;Growth;Hormonal;Hormones;Hour;Human;humanized mouse;Immune;immune activation;immune checkpoint blockade;Immune response;Immune signaling;immunoregulation;Immunotherapeutic agent;improved;In Vitro;in vivo;Infiltration;Injections;innate immune pathways;Innate Immune System;innovation;insight;Interferons;Knock-out;Left;Ligands;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;men;Metastatic Prostate Cancer;Molecular;mouse model;Mutation;Nature;NF-kappa B;novel;Nucleic Acids;overexpression;Pain;pain relief;palliative;Pathway interactions;patient subsets;Patients;Positioning Attribute;pre-clinical;preclinical study;Prediction of Response to Therapy;Process;Production;prostate biopsy;prostate cancer cell;prostate cancer cell line;Prostatic Neoplasms;PSA level;Quality of life;Receptor Signaling;Recurrence;Resistance;Resolution;Resources;response;Role;sensor;Serum;Sex Functioning;Signal Transduction;Stimulator of Interferon Genes;synergism;Testing;Testosterone;Therapeutic;tool;TP53 gene;translational approach;treatment duration;Treatment Efficacy;treatment response;tumor;tumor microenvironment;tumor-immune system interactions;Variant;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Androgen Activation of Innate Immune Signaling to Enhance Prostate Cancer Immune Response

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]