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;Climate-Related Exposures and Conditions;Clinical Research;Dementia;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PROJECT NARRATIVE Alzheimer’s disease and related dementias (ADRD) are a major public health problem, and evidence suggests experiences and the environment in early life might play an important role in development of ADRD. ADRD dis- proportionally affects Black and socially disadvantaged Americans, and our study assesses early-life social disadvantage including systemic racism and ambient air pollution as modifiable determinants of ADRD. Study results have the potential to identify key modifiable factors that affect ADRD and explain ADRD disparities.

PI_NAMEs: CASEY, JOAN A (contact);MAYEDA, ELIZABETH ROSE

PROGRAM_OFFICER_NAME: HARRELL, ERIN

PROJECT_TERMS: access restrictions;Affect;Age;Air Pollution;Alleles;Alzheimer's Disease;Alzheimer's disease related dementia;ambient air pollution;American;apolipoprotein E-4;Area;Black American;Black Populations;Black race;Brain;brain health;brain volume;Buffers;caucasian American;Censuses;Child;Classification;Cognitive;cognitive function;cognitive reserve;cognitive testing;Communities;Data;Data Linkages;Dementia;dementia risk;deprivation;Development;Disparity;early life exposure;early-life disadvantage;Education;Environment;Environmental Hazards;Environmental Risk Factor;Etiology;Evaluation;experience;Exposure to;fine particles;Genetic Risk;Genotype;Health;Health and Retirement Study;Impaired cognition;Incidence;Individual;Infant;innovation;Institutional Racism;Joints;late life;Life;Life Experience;Link;low socioeconomic status;Maps;Measures;Memory;Memory Loss;metropolitan;middle age;Modeling;neighborhood disadvantage;Neighborhoods;Nerve Degeneration;neuropathology;novel;older adult;Outcome;Participant;Pathology;performance tests;Play;Policies;Pollution;polygenic risk score;Population;Prevalence;prevent;processing speed;Public Health;Race;racial difference;racial disparity;Recording of previous events;Records;Research;residence;residential segregation;resilience;Risk Factors;Role;Sampling;segregation;social;social disparities;social factors;socioeconomic disadvantage;Socioeconomic Status;socioeconomics;Testing;Time;Work;young adult

PROJECT_TITLE: Historical social and environmental determinants of memory decline and dementia among U.S. older adults

STUDY_SECTION: SSPB

STUDY_SECTION_NAME: Social Sciences and Population Studies B Study Section[SSPB]


ADMINISTERING_IC: MH

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_FIPS: US

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: Narrative The prefrontal cortex exerts top-down control over other brain regions to regulate social behaviors, but the mechanisms have remained unclear. This project aims to understand the extent to which prefrontal neurons projecting to the posterior paraventricular thalamus regulate social motivation, and the role that parvalbumin interneurons may play in this process in both male and female mice. The results from this study will reveal a novel prefrontal circuitry in the regulation of sociability in sex-specific manner and provide novel insights into the sex differences in neural circuits that may go awry in psychiatric conditions where social motivation is significantly disrupted.

PI_NAMEs: GAO, WEN-JUN  (contact)

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Affect;Anxiety;autism spectrum disorder;Behavior;behavior test;Brain;Brain region;Calcium;Cells;clinically relevant;common symptom;Data;designer receptors exclusively activated by designer drugs;Dose;emotional behavior;Equilibrium;Exposure to;Female;Fiber;Genetic;genetic approach;Genetic Techniques;Home;Human;Image;Impairment;in vivo calcium imaging;insight;Interneurons;Investigation;Link;male;Medial;Mediating;Mental Depression;Mental disorders;Midline Thalamic Nuclei;Monitor;motivated behavior;Motivation;Mus;neural circuit;Neurons;neurotransmission;novel;Optics;optogenetics;Parvalbumins;patch clamp;Pathway interactions;Photometry;Physiological;Physiology;Pilot Projects;Play;Population;pre-clinical;preference;Prefrontal Cortex;Presynaptic Terminals;Process;Property;Publishing;Regulation;Reporting;Rewards;Rodent;Role;Same-sex;Schizophrenia;sex;Sex Differences;Shapes;Slice;social;Social Behavior;Social Conditions;social contact;Social Controls;social engagement;Social Interaction;Stimulus;Testing;Thalamic structure;Time;Transgenic Mice;Viral;Work

PROJECT_TITLE: Corticothalamic control of social motivation

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

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

ORG_CITY: CHICAGO

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARATIVE Analysis of rare somatic mutations in normal tissues is important for understanding the manifestation of normal phenotypes and the genetic disposition of human diseases. This project aims to detect mosaic mutations from scRNA-seq data generated by human cell atlas and many related projects to quantify their prevalence and functional effects on the rare mutated cells. Our bioinformatic tools provide a cost-effective way to construct a full picture of mosaic mutation atlas of human organs, to understand the effects of genomic diversification on cell functions within human body, and to develop novel strategies to prevent the clinical phenotype manifestations of human diseases.

PI_NAMEs: GAO, RULI  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Affect;Alleles;Atlases;Bayesian Method;bioinformatics tool;Biological Phenomena;Brain;Case Study;Cell Physiology;cell type;Cells;clinical phenotype;Computer software;computerized tools;Computing Methodologies;Copy Number Polymorphism;cost effective;Data;data resource;Data Set;Detection;Development;early onset;Ecosystem;Eye;Genetic;Genomics;Genotype;Goals;Heart;heart cell;Heart Diseases;Heart Transplantation;Human;Human body;human disease;human tissue;Individual;insight;Knowledge;Machine Learning;Malignant Neoplasms;Methods;Mitochondrial DNA;Modeling;mosaic variant;Mosaicism;Mutate;Mutation;Mutation Detection;Normal tissue morphology;novel;novel strategies;Organ;Phenotype;Point Mutation;Prevalence;prevent;Prevention strategy;Research;single-cell RNA sequencing;Somatic Mutation;synergism;Technology;Tissues;tool;transcriptome;Validation

PROJECT_TITLE: Single Cell Mosaic Mutation Atlas of Human Organ

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: ATLANTA

ORG_DEPT: ORTHOPEDICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative  The clinical use of Bone Morphogenetic Proteins (BMPs) for local bone induction in spine fusion but is often complicated but unwanted side effects. In this work we propose to locally inhibit the primary natural BMP antagonist, noggin, with a novel small molecule inhibitor and hybrid scaffolds creating a BMP-privileged zone that allows for lower BMP levels to induce bone formation. Together these strategies will provide a novel technology to safely and reliably induce spinal fusion.

PI_NAMEs: BODEN, SCOTT D. (contact);WILLETT, NICK J

PROGRAM_OFFICER_NAME: MARQUITZ, ARON

PROJECT_TERMS: Address;Animals;antagonist;Binding;Biocompatible Materials;Biological Assay;bioscaffold;BMP2 gene;bone;bone morphogenetic protein receptors;Bone Morphogenetic Proteins;Clinical;Collagen;collagen scaffold;Data;design;Dose;Drops;Engineering;Enzyme-Linked Immunosorbent Assay;Euthanasia;extracellular;Feedback;Formulation;Gene Expression Profiling;Glycolates;Harvest;Hematoma;Histologic;Histology;Hybrids;Implant;improved;In Vitro;in vivo;Inflammation;Inflammatory;innovation;irritation;Kinetics;Measures;Mechanics;Mediating;mineralization;Minerals;Modeling;Nanostructures;Nerve;new technology;novel;Operative Surgical Procedures;Oryctolagus cuniculus;Osteoblasts;Osteogenesis;osteogenic;osteoprogenitor cell;Palpation;Porifera;pre-clinical;prevent;Procedures;Process;Production;Proteins;radiological imaging;Rattus;receptor binding;recombinant human bone morphogenetic protein-2;recruit;Residual state;response;Safety;scaffold;Scanning;Seroma;side effect;Signal Pathway;Signal Transduction;Site;small molecule;small molecule inhibitor;soft tissue;spatiotemporal;Spinal Fusion;spine bone structure;subcutaneous;System;Testing;Time;Toxicology;Vascular Permeabilities;Work

PROJECT_TITLE: Small Molecule Inhibition of Noggin to Induce Spinal Fusion

STUDY_SECTION: SBSR

STUDY_SECTION_NAME: Skeletal Biology Structure and Regeneration Study Section[SBSR]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Genetics;Infectious Diseases;Microbiome

ORG_CITY: HOUSTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: PUBLIC HEALTH RELEVANCE STATEMENT This study will provide a deep insight into our understanding of oral pathogen Fusobacterium nucleatum- mediated coaggregation, which is driving force for formation and maturation of dental plaque. An uncontrolled dental plaque will develop periodontal disease. Our study will provide the design of new therapeutic strategies that prevent periodontal disease and complication associated with this notorious pathogen.

PI_NAMEs: WU, CHENGGANG  (contact)

PROGRAM_OFFICER_NAME: MCNEALY, TAMARA L

PROJECT_TERMS: Actinobacillus actinomycetemcomitans;Actinomyces;Address;Adhesions;Adult;American;Anaerobic Bacteria;ATF2 gene;Bacteria;Bacterial Adhesins;Binding;Butyrates;Catabolism;Cell Communication;Cell Density;Cells;Colorectal Cancer;Communicable Diseases;Communities;Complex;Complication;Data;Dental Plaque;design;Development;Disease;driving force;Environment;Enzymes;Exhibits;Experimental Models;fitness;Fusobacterium;Fusobacterium nucleatum;Gene Deletion;Gene Expression;Genes;Genetic;Genetic Transcription;Genome;Goals;Health;In Vitro;insight;Investigation;Libraries;Link;Lysine;Mediating;microbial;Microbial Biofilms;microbial community;microbiome;microorganism;Mouth Diseases;mutant;Mutate;Names;novel;novel therapeutic intervention;Odontogenesis;Operon;Oral;oral bacteria;oral biofilm;oral microbial community;Oral Microbiology;oral pathogen;Organism;pathogen;Pathogenicity;Pathway interactions;Periodontal Diseases;Periodontitis;polymicrobial biofilm;Porphyromonas gingivalis;Premature Birth;prevent;Probability;Process;Proliferating;promoter;public health relevance;receptor;Regulation;Research;response;RNA;Role;screening;Signal Pathway;Signal Transduction;social;Streptococcus;Surface;System;Testing;Therapeutic;Time;Untranslated RNA;VAI-2;Work

PROJECT_TITLE: Regulation in Fusobacterium-mediated coaggregation

STUDY_SECTION: ODCS

STUDY_SECTION_NAME: Oral, Dental and Craniofacial Sciences Study Section[ODCS]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Frontotemporal Dementia (FTD);Lewy Body Dementia;Neurodegenerative;Neurosciences;Parkinson's Disease;Prevention

ORG_CITY: BIRMINGHAM

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative The overall goal of our project is to validate diagnostic tools for Alzheimer’s disease and related dementias such as tauopathies, Lewy body dementia, and their comorbidities affecting millions of people in the U.S. Our study may ultimately help early diagnosis to improve patient care and aid the development of therapeutics for patients living with dementias.

PI_NAMEs: CHEN, SHU G. (contact)

PROGRAM_OFFICER_NAME: ROVESCALLI, ALESSANDRA C

PROJECT_TERMS: accurate diagnosis;Affect;Age;alpha synuclein;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease patient;Alzheimer's disease related dementia;Amyloid beta-Protein;Autopsy;biobank;Biological Assay;Biological Markers;Biopsy;Biopsy Specimen;Brain;Brain imaging;brain tissue;Cadaver;Clinic;Clinical;clinical diagnosis;clinical practice;Collection;comorbidity;Consensus;corticobasal degeneration;corticobasal syndrome;Dementia;Dementia with Lewy Bodies;Deposition;Detection;Development;Diagnosis;diagnostic assay;diagnostic biomarker;Diagnostic tests;diagnostic tool;Differential Diagnosis;Disease;Disease Progression;early detection biomarkers;Early Diagnosis;Emerging Technologies;follow-up;Goals;illness length;Immunoassay;improved;Lewy Body Dementia;Measures;Memory;neuropathology;new technology;novel marker;Outcome;Outcome Study;Parkinson Disease;Parkinson's Dementia;Participant;Pathologic;Pathology;Patient Care;Patients;Peripheral;Persons;Positioning Attribute;prion-like;Probability;Progressive Supranuclear Palsy;prospective;protein aggregation;recruit;Registries;Research;Resources;Sampling;Severity of illness;sex;Skin;skin biopsy;Specimen;success;Symptoms;synucleinopathy;tau aggregation;tau Proteins;tau-1;Tauopathies;Testing;therapeutic development;Time;Validation;Visit

PROJECT_TITLE: Peripheral Biomarkers for Early Diagnosis of Mixed Pathologies in AD/ADRD

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


NIH_SPENDING_CATS: Back Pain;Chronic Pain;Clinical Research;Neurosciences;Pain Research;Physical Rehabilitation;Rehabilitation

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Spinal muscles have a uniquely important biomechanical role in stabilizing the lumbar spine and could provide a safe and effective treatment target for alleviating chronic low back pain; however, how spinal muscles degrade and begin to turn into fat in patients with chronic low back pain is unknown. This study will create a new approach to observe patterns of fat in the spinal muscles using advanced MRI methods, and then relate these fat patterns with patient movement patterns and types of molecules within the muscle tissue. Understanding why spinal muscles degrade and how spinal health relates to disability associated with chronic low back pain will support the advancement of new therapeutics and treatments targeting the muscles.

PI_NAMEs: BAILEY, JEANNIE FERN (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: 3-Dimensional;Affect;Age;Astronauts;Atrophic;Biomechanics;Biometry;Biopsy;Chronic low back pain;clinical imaging;clinically relevant;Complex;Data;Deformity;disability;Disabling;effective therapy;Electromyography;Exposure to;Fatigue;Fatty acid glycerol esters;Fibrosis;Functional disorder;functional outcomes;Future;Gene Expression Profile;Genes;Health;imaging biomarker;improved;improved outcome;Infiltration;Inflammatory;Inflammatory Response;Injections;Intervertebral disc structure;intervertebral disk degeneration;kinematics;Longitudinal Studies;Machine Learning;Magnetic Resonance Imaging;Maps;Measurement;Methods;Molecular;motor control;Movement;Muscle;muscle degeneration;Muscle Development;muscle regeneration;neuromuscular;novel;novel strategies;novel therapeutics;Operative Surgical Procedures;Pain management;pain patient;pain symptom;Pathology;Pathway Analysis;Patient Selection;Patients;Pattern;Phenotype;Positioning Attribute;Posture;prescription opioid;prevent;Procedures;rehabilitation strategy;response;Risk;Role;Rotation;Slipped Disk;Space Flight;Spatial Distribution;Spinal;stem cells;Structure;Structure-Activity Relationship;Surface;Symptoms;System;Testing;Therapeutic;Time;Tissue Sample;tool;transcriptome;Uncertainty;Vertebral column;Walking;wearable sensor technology;Work

PROJECT_TITLE: Mechanistic structure-function relationships for paraspinal muscle fat infiltration in chronic low back pain patients

STUDY_SECTION: MRS

STUDY_SECTION_NAME: Musculoskeletal Rehabilitation Sciences Study Section[MRS]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Kidney Disease;Orphan Drug;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: PROJECT NARRATIVE In 2015, then-President Barack Obama launched the Precision Medicine Initiative, which dictated a patient- powered emerging approach to disease prevention and treatment that takes into account individual differences in people's genes, environment, and lifestyles – making possible more effective, targeted treatments for diseases. In personalized medicine, biomarkers serve as indicators of disease prognosis and can potentially predict a patient's response to drug treatment, thereby informing clinical decisions and aiding risk stratification. Currently, there are no established biomarkers to guide treatment of metastatic renal cell carcinoma, a disease with many drugs with distinct mechanisms of action approved for first-line use. The establishment of robust biomarkers that can reliably identify which patients will benefit from immune checkpoint inhibitor therapies in the first-line setting would bring us closer to the overarching target of the Precision Medicine Initiative, and also reduce toxicities, lower treatment costs, and improve health-related quality of life in patients diagnosed with metastatic renal cell carcinoma.

PI_NAMEs: CHOUEIRI, TONI  (contact);SIGNORETTI, SABINA

PROGRAM_OFFICER_NAME: MCKEE, TAWNYA C

PROJECT_TERMS: Accounting;adaptive immunity;Address;Allogenic;anti-PD-1;Antigens;arm;Biological Markers;Biology;cancer type;candidate marker;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;Characteristics;checkpoint inhibition;checkpoint therapy;Clear cell renal cell carcinoma;Clinical;Clinical Trials;clinically relevant;Combined Modality Therapy;Data;Decision Making;Dedications;Diagnosis;Disease;disease prognosis;disorder prevention;Effectiveness;Endogenous Retroviruses;Endothelial Growth Factors Receptor;Environment;Epitopes;exhaust;experience;Genes;Goals;Guidelines;health related quality of life;high dimensionality;IFIH1;Immune;immune activation;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;Immunity;Immunologic Markers;Immunological Models;immunoregulation;Immunosuppression;Immunotherapy;improved;Individual Differences;Infiltration;ipilimumab;Life Style;Localized Disease;Malignant Neoplasms;Metastatic Renal Cell Cancer;multidisciplinary;Myeloid Cells;Myeloid-derived suppressor cells;National Comprehensive Cancer Network;Natural Immunity;Neoplasm Metastasis;Nivolumab;novel;Outcome;Pathology;Pathway interactions;patient response;Patient risk;patient subsets;Patient-Focused Outcomes;Patients;PD-1 blockade;Peptides;personalized medicine;Persons;Pharmaceutical Preparations;Pharmacotherapy;Phase;phase III trial;Phenotype;Physicians;Precision Medicine Initiative;predictive modeling;programmed cell death protein 1;Progression-Free Survivals;Randomized;Randomized, Controlled Trials;Recommendation;Regulatory T-Lymphocyte;Renal Carcinoma;Renal Cell Carcinoma;Resistance;response;response biomarker;risk stratification;Role;Specimen;standard of care;Stem cell transplant;Stimulator of Interferon Genes;success;T-Lymphocyte;Testing;Tissue Sample;Tissues;Toxic effect;transcriptome sequencing;translational scientist;Treatment Cost;tumor;Tumor Antigens;Tumor Immunity;tumor microenvironment;Tumor Tissue;tumor-immune system interactions;Vascular Endothelial Growth Factors;Vertebral column

PROJECT_TITLE: Tissue-based biomarkers of anti-PD-1-based therapy in metastatic renal cell carcinoma

STUDY_SECTION: CBSS

STUDY_SECTION_NAME: Cancer Biomarkers Study Section[CBSS]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: Cambridge

ORG_NAME: CEREVEL THERAPEUTICS, LLC

PHR: PROJECT NARRATIVE Preclinical data have demonstrated that antagonism of kappa opioid receptors (KOR) is efficacious in reducing the physical symptoms of opioid withdrawal. Currently, the alpha 2-adrenergic agonist lofexidine is the only approved therapy for the mitigation of the physical symptoms of opioid withdrawal but it is only modestly effective and can have significant unwanted side effects. In this application, Cerevel Therapeutics has identified a novel selective KOR antagonist with unique properties and good preclinical safety margins that we are planning to take through early human safety/pharmacokinetics and occupancy studies, into a Phase 2 study to assess efficacy in acute opioid withdrawal.

PI_NAMEs: SUIDAN, GEORGETTE  (contact)

PROGRAM_OFFICER_NAME: WHITE, DAVID A

PROJECT_TERMS: Abstinence;abuse liability;Acute;Address;Adrenergic Agonists;Adult;Affective;Affinity;Agonist;analytical method;Animals;antagonist;Anxiety;Area;Attenuated;Award;Brain;carfentanil;Central Nervous System Depressants;Chemistry;Chemosensitization;child bearing;Chronic;Clinic;Clinical;Clinical Research;clinically significant;Data;design;Development;developmental toxicity;Dopamine;Dose;drug abstinence;Drug abuse;Drug Kinetics;drug seeking behavior;drug withdrawal;Drug Withdrawal Symptoms;Dynorphins;effective therapy;efficacy evaluation;Electrocardiogram;first-in-human;Formulation;Fright;Funding;Funding Opportunities;Future;Good Manufacturing Process;Grant;healthy volunteer;Human;human data;Hypotension;kappa opioid receptors;Laboratories;Laboratory Finding;lofexidine;manufacture;manufacturing process;Measures;Mediating;Mental Depression;Modeling;Motivation;mu opioid receptors;Mus;novel;Opioid;Opioid agonist;Opioid Antagonist;opioid use disorder;opioid withdrawal;Oral;Orthostasis;Output;Oxycodone;Pathologic;patient population;Pharmaceutical Preparations;Pharmacologic Substance;Phase;phase 2 study;Phase II Clinical Trials;physical symptom;Physiological;Positioning Attribute;Positron-Emission Tomography;pre-clinical;Pre-Clinical Model;preclinical safety;Property;receptor;Receptor Signaling;Receptors, Adrenergic, alpha-2;Regimen;Relapse;reproductive toxicity;Research;Rewards;Rodent;Running;Safety;safety assessment;safety study;Sedation procedure;Serious Adverse Event;Severities;side effect;spiradoline;standard of care;Stress;Syncope;Therapeutic;Up-Regulation;Withdrawal;Withdrawal Symptom;Woman;Work

PROJECT_TITLE: CVL-354, a kappa opioid receptor antagonist for treatment of opioid use disorder, withdrawal and relapse

STUDY_SECTION: NIDA

STUDY_SECTION_NAME: Medication Development Research Study Section[NIDA-L]


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

ORG_CITY: GAINESVILLE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Estrogen receptor positive breast cancer can be treated with anti-hormone therapies, but de novo and acquired resistance are common. The goal of this proposal is to understand the molecular mechanisms of how different classes of estrogen receptor antagonists inhibit breast cancer growth and how expression of the epidermal growth factor receptor can cause resistance to tamoxifen.

PI_NAMEs: NETTLES, KENDALL W (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Address;Agonist;antagonist;Aromatase Inhibitors;Binding;Biological Markers;Biology;bone;Breast Cancer Cell;Breast Cancer therapy;cell growth;Cell Nucleus;Cells;Charcoal;Chemicals;ChIP-seq;Clinical;Code;Confocal Microscopy;Disease;effective therapy;Endocrine;Enzymes;Epidermal Growth Factor Receptor;Estradiol;Estrogen receptor positive;Estrogen Receptors;Fulvestrant;Gene Expression;gene network;gene repression;Genes;genetic corepressor;Genetic Transcription;Goals;Growth;Growth Factor;Growth Factor Receptors;Histones;hormone therapy;in vivo;inhibitor;Ligands;Malignant Breast Neoplasm;MAP Kinase Gene;Mediating;Modality;Modeling;Molecular;Molecular Conformation;novel therapeutics;overexpression;Pathway interactions;Patients;PIK3CG gene;Postmenopause;Premenopause;prevent;Proliferating;Proteins;Proteomics;receptor;Receptor Protein-Tyrosine Kinases;Receptor Signaling;Regulation;Resistance;response;scaffold;Selective Estrogen Receptor Modulators;Signal Pathway;Signal Transduction;Tamoxifen;targeted cancer therapy;targeted treatment;Testing;tool;transcription factor;Transcriptional Regulation;Western Blotting;Woman

PROJECT_TITLE: Mechanisms of estrogen receptor ligand signaling

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences;Sleep Research

ORG_DEPT: NEUROLOGY

PHR: Narrative Quality sleep is a fundamental necessity for maintaining health and optimal cognitive functioning. Our program aims to understand how the brain and nervous system regulate our sleep quality/efficiency and then use that knowledge to reduce the burden of neurological diseases (perhaps all diseases) for all people in our aging society.

PI_NAMEs: FU, YING-HUI  (contact)

PROGRAM_OFFICER_NAME: HE, JANET

PROJECT_TERMS: Aging;Alzheimer's Disease;Brain;brain cell;Brain Mapping;Brain region;cognitive function;Development;Disease;Genes;Genetic;Health;Hour;Human;Individual;Knowledge;Life;Longevity;Molecular;mouse model;Mutation;Nervous System;Nervous System Disorder;Neurodegenerative Disorders;Pathology;Pathway interactions;Persons;Population;prevent;Probability;programs;protective effect;Psyche structure;Regulation;Research;Sleep;Sleep Deprivation;sleep quality;sleep quantity;sleep regulation;Societies;Solid;System;Time;trait

PROJECT_TITLE: Investigating sleep efficiency mechanism and its impact on diseases


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Dental, Oral, and Craniofacial Disease;Infectious Diseases

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Dental health is critical to quality of life, but the tools that dentists and periodontists use to inspect the mouth have major limitations related to studying the gingiva. This work will build an ultrasound-based device to non- invasively map and measure periodontal disease easily, earlier, and more accurately. The imaging approach will evaluate the entire pocket and be less variable than the existing method—this will improve quality of life.

PI_NAMEs: JOKERST, JESSE VINCENT (contact)

PROGRAM_OFFICER_NAME: FISCHER, DENA

PROJECT_TERMS: 3-Dimensional;3D Print;acoustic imaging;Algorithms;alveolar bone;American;Bicuspid;biotypes;bone;Cadaver;California;Canis familiaris;Cardiovascular Diseases;Clinical;Clinical assessments;clinical translation;Collaborations;commercialization;Complement;Consumption;Data;Dental;Dental Care;Dental Enamel;Dental General Practice;Dentists;design;Devices;Diagnosis;Dimensions;Disease;Dose;Endoscopic Ultrasonography;Endoscopy;Equipment;Family suidae;Frequencies;Funding;Gingiva;Goals;Gold;Head and neck structure;Health;Health Professional;Hockey;Housing;Human;human data;human disease;human subject;Hypoxia;Image;image processing;imaging approach;Imaging Device;imaging system;Imaging technology;Implant;improved;in vivo imaging system;Incisor;Industrialization;industry partner;Inflammation;innovation;insight;Investments;Ionizing radiation;Jaw;Lasers;Lateral;Letters;Licensing;Light;Malignant Neoplasms;Maps;Measurement;Measures;meter;Methods;miniaturize;miniaturized device;Modality;Monitor;Mouth Diseases;Neck Disorder;Needles;non-invasive imaging;Operative Surgical Procedures;Oral cavity;Oral health;Outcome;Pain;Patients;Performance;Perfusion;Periodontal Diseases;Periodontitis;Periodontium;photoacoustic imaging;Physiologic pulse;Prevalence;Process;Provider;Quality of life;radiological imaging;Recording of previous events;Rectum;Resolution;Risk;soft tissue;Source;standard of care;Surface;System;Technology;technology validation;Thick;Time;Tissues;tool;Tooth Cervix;Tooth Loss;Tooth structure;Transducers;Translating;treatment planning;Ultrasonic Transducer;Ultrasonography;ultrasound;United States National Institutes of Health;Universities;Vagina;Validation;Variant;Widespread Disease;Work

PROJECT_TITLE: A Miniaturized and High-frequency Acoustic Imaging System for Oral Health and Diseases of the Head and Neck


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Genetic Testing;Genetics;Health Services;Human Genome;Prevention;Primary Health Care;Telehealth

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: PROJECT NARRATIVE The objective of this study is to assess the impact of a new cancer genetic counseling model that leverages the increasing digitization of healthcare on psychosocial, behavioral, and implementation outcomes. This will be achieved through a digitally-enhanced intervention to promote cascade testing for the at-risk relatives of probands with pathogenic/likely pathogenic variants (PV), and the optimal follow-up care of those with a variant of uncertain significance (VUS). This project has the potential to improve care for patients with a PV and their families, and patients with a VUS, and will ultimately be applicable to the practice of genetic counseling and genomic medicine across diseases and clinical settings.

PI_NAMEs: HAMILTON, JADA GABRIELLE;OFFIT, KENNETH  (contact)

PROGRAM_OFFICER_NAME: RIDER, RENEE ANNE

PROJECT_TERMS: Address;Appointment;arm;Authorization documentation;behavioral outcome;cancer genetics;cancer predisposition;cancer risk;care delivery;Caring;cascade genetic testing;Classification;Clinical;cognitive interview;Communication;comparative effectiveness;Confusion;Continuity of Patient Care;cost;Decision Making;digital;digital platform;digital technology;digital tool;Disclosure;Disease;disease-causing mutation;Education;Educational Materials;Effectiveness;Emotional;Ensure;Evaluation;experience;experimental study;Face;Family;Feedback;Focus Groups;follow-up;gene panel;Genes;Genetic;Genetic Counseling;Genetic Enhancement;genetic pedigree;genetic testing;Genomic medicine;Healthcare;hereditary risk;implementation cost;implementation intervention;implementation outcomes;Implementation readiness;improved;Individual;Intervention;intervention cost;Linguistics;Mediating;Medical;Memorial Sloan-Kettering Cancer Center;Modeling;Needs Assessment;non-genetic;Notification;novel;Outcome;outreach;Participant;Pathogenicity;Patient Care;Patients;Periodicals;Persons;Population;primary care provider;proband;prospective;Provider;psychosocial outcome;Quality of Care;Randomized;Randomized, Controlled Trials;Recommendation;Recontacts;Recording of previous events;Relative Risks;Research;Research Design;response;Risk;Saliva;Schedule;Service delivery model;Services;standard of care;stressor;Surveys;Technology;telegenetics;Testing;testing uptake;Time;tool;treatment arm;trial design;Uncertainty;Update;uptake;Variant;variant of unknown significance;Work

PROJECT_TITLE: Digital Technology to Enhance Access to and Effectiveness of Cancer Genetic Counseling


NIH_SPENDING_CATS: Behavioral and Social Science;Digestive Diseases;Drug Abuse (NIDA only);HIV/AIDS;Hepatitis;Hepatitis - C;Infectious Diseases;Liver Disease;Microbiome;Opioid Misuse and Addiction;Opioids;Prevention;Substance Misuse

ORG_CITY: BALTIMORE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Despite decades of investigation into behavioral drivers, understanding the gradient of HIV risk among people who inject drugs (PWID) and designing effective tools to predict this risk remains a challenge. This study will evaluate novel use of the plasma virome as a sentinel bioindicator of HIV risk, as well as elucidate whether the virome can reveal potential transmission networks before HIV infection occurs. This represents a particularly innovative approach to HIV treatment and prevention and may lead to more robust molecular surveillance methods that can guide public health officials in targeting interventions to prevent HIV outbreaks and focus limited resources for the greatest impact.

PI_NAMEs: CLIPMAN, STEVEN J.;KANDATHIL, ABRAHAM  (contact)

PROGRAM_OFFICER_NAME: BORGMANN, KATHLEEN RUTH

PROJECT_TERMS: Accounting;Acquired Immunodeficiency Syndrome;Acute Hepatitis C;Africa South of the Sahara;AIDS prevention;Baltimore;Behavioral;Benign;Biological;Blood;Blood specimen;case control;case finding;cohort;Cohort Studies;Country;County;Data;design;Disease Outbreaks;disorder control;DNA;Drug usage;Epidemic;Epidemiology;Equipment;Event;experience;General Population;Grant;Hepatitis C;Hepatitis C Acquisition;Hepatitis C Incidence;Hepatitis C virus;Heroin;High Prevalence;high risk;HIV;HIV Infections;HIV risk;HIV Seropositivity;HIV/HCV;Human;Incidence;India;Indiana;Individual;Injecting drug user;injection drug use;Injections;innovation;Interruption;Intervention;Investigation;Legal;Link;low and middle-income countries;Measures;Medical;medical complication;meetings;Methods;Modeling;Molecular;mortality;nanopore;Needle Sharing;Needle-Exchange Programs;new pandemic;next generation sequencing;novel;opioid overdose;opioid use;Overdose;Participant;Patient Self-Report;Persons;Pharmaceutical Preparations;Phylogenetic Analysis;Plasma;Population;Population Surveillance;predictive tools;prescription opioid;Prevalence;prevent;prevent outbreaks;Prevention;prevention service;Preventive measure;programs;prospective;Public Health;reconstruction;Research;Research Personnel;Resources;response;Risk;Risk Factors;risk prediction;RNA;rural counties;Sampling;San Francisco;Sentinel;social;Social Network;social stigma;Specimen;substance use;success;Surveillance Methods;System;Testing;Thailand;tool;transmission process;United States;virome;Virus;Work

PROJECT_TITLE: Leveraging the plasma virome as a biological indicator of HIV risk and transmission networks among people who inject drugs

STUDY_SECTION: HCCS

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Bioengineering;Clinical Research;Palliative Care;Patient Safety

ORG_CITY: MADISON

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE This project aims to improve the care of older adults by characterizing and identifying systems-level practice patterns that lead to the initiation of life-supporting treatments for patients with life-limiting illness. A deeper understanding of institutional routines and forces driving care might allow us to identify misaligned incentives and specific moments when interventions can be employed to disrupt patterns that lead to overtreatment at the end of life. The research and training proposed for this Midcareer Investigator's Award will support Dr. Schwarze as she builds a new direction of research and expands her mentorship activities for an increasing number of young investigators who aim to develop a career in patient-oriented and aging research.

PI_NAMEs: SCHWARZE, MARGARET  (contact)

PROGRAM_OFFICER_NAME: BAKOS, ALEXIS DIANE

PROJECT_TERMS: acute care;Administrator;advanced dementia;Affect;Aging;Anthropology;Award;Behavioral;career;career development;Caregivers;Caring;Clinical;clinical decision-making;Cognitive;Communication;Communication Tools;comparative;Coupled;Decision Making;Development Plans;Diagnosis;Dialysis procedure;driving force;end of life;end of life care;Engineering;Enteral Feeding;Environment;Event;experience;Exploratory/Developmental Grant for Diagnostic Cancer Imaging;Family member;financial incentive;Future;Goals;hands on research;Healthcare;Human;improved;Incentives;informant;innovation;Institution;interest;Intervention;Interview;K-Series Research Career Programs;Laboratories;Life;Link;Mechanical ventilation;Medical;Mentors;Mentorship;Methodology;Methods;Modeling;novel;Observational Study;older adult;older patient;Outcome;overtreatment;palliative;Palliative Care;Pathway interactions;Patient Care;patient oriented;patient oriented research;patient population;Patient Preferences;patient safety;patient-clinician communication;Patients;Pattern;Patterns of Care;Play;Positioning Attribute;practice setting;preference;Process;programs;Psychology;Quality of Care;Research;Research Personnel;Research Support;Resources;Role;shared decision making;skills;social;success;Surgeon;Surgical Intensive Care;Surveys;Symptoms;System;Technology;Testing;theories;therapy design;Time;Training;user centered design;Vascular Diseases;Work

PROJECT_TITLE: Use of systems engineering to evaluate the initiation of life-supporting treatments in older adults with life-limiting illness

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Clinical Aging Study Section[NIA-C]


NIH_SPENDING_CATS: Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Cancer;Liver Disease;Rare Diseases

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Project Narrative The proposed research examines the role of BNIP3, BNIP3L and mitophagy in control of lipid metabolism in the liver, de-regulation of which has significance for understanding the link between fatty liver disease and hepatocellular carcinoma.

PI_NAMEs: MACLEOD, KAY F (contact)

PROGRAM_OFFICER_NAME: WILLIS, KRISTINE AMALEE

PROJECT_TERMS: Address;Aging;Amino Acids;BCL2/Adenovirus E1B 19kd Interacting Protein 3-Like;Binding;Biological Markers;BNIP3L gene;Cancer Etiology;cell growth;Cessation of life;Clinic;Data;Detection;Development;Disease;Disease Management;Disease Progression;Etiology;fatty acid metabolism;fatty acid oxidation;Fatty Liver;fatty liver disease;FRAP1 gene;Genes;Glucagon;Grant;Growth;Guanosine Triphosphate Phosphohydrolases;hepatocellular carcinoma cell line;Hepatocyte;Homeostasis;Human;improved;Incidence;inhibitor;insight;Knock-out;Link;lipid metabolism;Lipids;Liver;liver cancer model;liver function;liver metabolism;Lobule;Lysosomes;Malignant neoplasm of liver;Metabolic;Mitochondria;mitochondrial dysfunction;Molecular;mouse model;mTOR inhibition;mTOR Inhibitor;mTOR Signaling Pathway;neoplastic cell;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;Nutrient;Nutrient availability;nutrient deprivation;Obesity Epidemic;Overnutrition;Patient-Focused Outcomes;Pattern;Phosphotransferases;prevent;Primary carcinoma of the liver cells;Process;Proteomics;receptor;Regulation;Research;response;Role;Sampling;Signal Transduction;Societies;Testing;tumor growth;Tumor Suppressor Proteins;tumorigenic;United States;Work

PROJECT_TITLE: BNIP3 and BNIP3L (NIX) in lipid homeostasis and growth control in the liver

STUDY_SECTION: CCB

STUDY_SECTION_NAME: Cancer Cell Biology Study Section[CCB]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

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

ORG_CITY: PULLMAN

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: WASHINGTON STATE UNIVERSITY

ORG_STATE: WA

PHR: PROJECT NARRATIVE A key impediment to recovery from cocaine use disorder is that exposure to cocaine-associated environments can trigger drug-associated memories and consequent profound craving. The proposed project aims to increase our understanding of hippocampal cellular mechanisms and synaptic plasticity mechanisms that maintain cocaine memories over time. The long-term goal of this research is to provide insight into how the neurobiological underpinnings of pathologically strong and invasive cocaine memories can be targeted for drug-relapse prevention.

PI_NAMEs: FUCHS LOKENSGARD, RITA A (contact)

PROGRAM_OFFICER_NAME: NAIR, SUNILA GOPI

PROJECT_TERMS: Abstinence;Animal Model;Basic Science;Behavior;cell type;Cells;Cocaine;cocaine exposure;cocaine seeking;Cocaine use disorder;craving;Data;dentate gyrus;Development;Dorsal;drug craving;Drug Modelings;drug relapse;drug seeking behavior;Drug Targeting;effective therapy;Electrophysiology (science);Environment;Exhibits;Exposure to;Future;Genetic Recombination;Glutamates;Goals;Hippocampal Formation;hippocampal pyramidal neuron;Hippocampus;Immunohistochemistry;Impairment;in vivo;Individual;insight;interest;Interneurons;Label;Literature;long term memory;Maintenance;Maps;Memory;memory recall;memory retrieval;Mental disorders;Molecular;mossy fiber;Motivation;neural;neural circuit;Neurobiology;Neuronal Plasticity;novel;optogenetics;Output;patch clamp;Pathologic;Pathway interactions;Pharmaceutical Preparations;Pharmacology;Phenotype;Play;Population;preservation;prevent;Process;Protein Biosynthesis;Protocols documentation;Publishing;Pyramidal Cells;Recovery;Relapse;relapse prevention;Research;response;Rest;Retrieval;Rhodopsin;Role;src-Family Kinases;Stimulus;Stratum Lucidum;Subgroup;Substance Use Disorder;Synapses;Synaptic plasticity;System;Testing;Therapeutic;therapeutic target;therapeutically effective;therapy development;Time;transmission process;Update;Work

PROJECT_TITLE: Hippocampal mechanisms of cocaine-memory reconsolidation

STUDY_SECTION: MCNP

STUDY_SECTION_NAME:
Molecular and Cellular Neuropharmacology Study Section
[MCNP]


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Hematology;Immunotherapy;Orphan Drug;Pediatric;Pediatric Cancer;Prevention;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: ANN ARBOR

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PUBLIC HEALTH RELEVANCE STATEMENT Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for many malignant hematological conditions, but its broader application has been limited by a serious complication known as graft-versus-host disease (GVHD). Novel drugs are continually being tested in clinical trials to identify more effective therapies to mitigate GVHD. However, there remains an urgent and major unmet need of providing children, adolescents, and young adults access to clinical trials examining novel GVHD prevention strategies as well as assessing their impact on parameters important to reintegration into society after transplantation, such as neurocognitive function and health-related quality of life.

PI_NAMEs: CHOI, SUNG WON  (contact)

PROGRAM_OFFICER_NAME: HENDERSON, LORI A

PROJECT_TERMS: Activities of Daily Living;Acute Graft Versus Host Disease;Adolescent and Young Adult;Adult;Age;aged;Algorithms;Allogenic;arm;Attenuated;attenuation;Biological;Biological Process;Biological Products;Cell-Mediated Cytolysis;Child;Childhood;Clinical;Clinical Data;clinical practice;Clinical Trials;Cognition;cognitive function;cognitive testing;Complication;conditioning;Coupled;curative treatments;cytokine;Data;design;Development;Disadvantaged;disorder prevention;Dose;Drug Kinetics;early phase trial;effective therapy;Enrollment;first-in-human;Functional disorder;Funding;Funding Opportunities;Future;Goals;graft vs host disease;graft vs leukemia effect;Grant;health related quality of life;Hematology;Hematopoietic Stem Cell Transplantation;Histone Deacetylase Inhibitor;immunomodulatory therapies;Immunosuppression;Impaired cognition;improved;Incidence;Inflammatory;Inflammatory Response;Infrastructure;insight;Intervention;investigator-initiated trial;Knowledge;Laboratory Study;Life;Malignant - descriptor;Maximum Tolerated Dose;Measures;member;Morbidity - disease rate;mortality;mouse model;multidisciplinary;Neurocognitive;neuroprotection;novel;novel strategies;novel therapeutics;Outcome;Patient Outcomes Assessments;patient population;Patient Self-Report;Patients;pediatric patients;Pharmacodynamics;Phase;Phase I/II Clinical Trial;Phase I/II Trial;phase II trial;Population;pre-clinical;preclinical study;preservation;prevent;prevention clinical trial;Prevention strategy;Property;prophylactic;Prophylactic treatment;public health relevance;Randomized Controlled Clinical Trials;Recommendation;Regulatory T-Lymphocyte;Research;Resources;Role;Safety;Sampling;skills;Societies;T-Lymphocyte;targeted agent;Testing;Tissues;Transplant Recipients;Transplantation;Vorinostat;Work

PROJECT_TITLE: Phase I/II clinical trial of HDAC inhibition for GVHD prevention in children, adolescents, and young adults

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


ADMINISTERING_IC: DK

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Diarrheal diseases cause millions of deaths each year and enteric viruses, such as human norovirus, significantly contribute to these cases. Due to the unavailability of conventional cell culture adaptations and animal models, mechanistic human norovirus studies remain lacking. This proposal uses a surrogate virus and human intestinal organoid systems to determine the calcium signaling dysregulation that occurs during norovirus infection and the role that this plays in viral pathogenesis and replication, ultimately unveiling key parallels between enteric viruses that can be exploited for broad spectrum antiviral therapies.

PI_NAMEs: SCRIBANO, FRANCESCA JEAN (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: Acute;Animal Model;Anti-viral Therapy;Antidiarrheals;Biological Models;Calcium;Calcium Channel;Calcium Oscillations;Calcium Signaling;Calicivirus;Calicivirus Infections;Cell Culture Techniques;Cell Physiology;Cell Signaling Process;Cells;Cessation of life;chelation;Clinical;Communication;cytokine;Data;Development;diarrheal disease;Disease;Disease Progression;Dose;Enteral;enteric pathogen;experience;extracellular;Family;Fluids and Secretions;Functional disorder;Gastroenteritis;Genetic;global health;Growth;Human;Image;Infection;Innate Immune Response;insight;Intestines;Ion Channel;Knock-out;Knowledge;Link;Liquid substance;Measures;Mediating;member;monolayer;Norovirus;novel;Organoids;paracrine;Paracrine Communication;Pathway interactions;pharmacologic;Phenotype;Play;Prevalence;Proteins;Purinoceptor;rational design;Reoviridae;Reovirus;response;Role;Rotavirus;Rotavirus Infections;Serotonin;Signal Pathway;Signal Transduction;societal costs;System;Testing;Therapeutic;Transfection;Vaccines;Viral;Viral Gastroenteritis;Viral Pathogenesis;Virus;Virus Diseases;Virus Replication;Work

PROJECT_TITLE: Calcium signaling in Calicivirus infection and replication


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

PHR: Pathologic α-synuclein spreading from the gut to the brain is an important driver to aging-associated α- synucleinopathy, a group of neurodegenerative diseases with no effective therapy. It remains largely unknown how aging-associated blood-borne components modulate the initiation and progression of α-synucleinopathy. Using the heterochronic blood exchange (HBE) approach, we will study how two aging-associated HBE- modulated plasma proteins (FGL1 and sLAG3) affect the pathogenesis of α-synucleinopathy. If successful, our discoveries will facilitate the development of early diagnosis and therapy for α-synucleinopathy, based on detecting and modulating these two blood-borne aging-associated factors. Our ultimate goal is to discover new ways to help people live longer healthier lives by modulating rejuvenation and age-acceleration factors.

PI_NAMEs: MAO, XIAOBO  (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Accounting;Affect;age acceleration;age related;age related decline;Aging;aging mechanism;aging related;aging reversal;alpha synuclein;Alzheimer's Disease;Alzheimer's disease patient;Anxiety;Automobile Driving;Autopsy;Behavioral;Blood;Brain;Brain region;Cells;Central Nervous System;Clinical;clinical translation;Cognition;Cognitive;common symptom;Dementia;Dementia with Lewy Bodies;Development;Disease;Disease Progression;Early Diagnosis;Early treatment;effective therapy;Enteral;Event;Exhibits;experimental study;Fibrinogen;Foundations;gain of function;gastrointestinal system;Gastrointestinal tract structure;Gene Activation;Genetically Engineered Mouse;Goals;gut-brain axis;Human;Impaired cognition;Impairment;Inflammation;Injections;insight;Knockout Mice;Knowledge;Ligands;loss of function;Lymphocyte Activation;Mediating;Mediation;Mediator;Memory impairment;Mental Depression;Modeling;Molecular;Molecular Profiling;Moods;motor disorder;mouse model;Mus;Nerve Degeneration;Nerve Fibers;Nervous System;Neurodegenerative Disorders;neuroinflammation;novel;novel strategies;old mice;Organ;Paper;Parkinson Disease;Parkinson's Dementia;Pathogenesis;Pathogenicity;Pathologic;Pathology;Patients;Peripheral Nervous System;Persons;Phenotype;Plasma;Plasma Proteins;prevent;prion-like;pro-aging;protein function;Proteins;receptor;Recombinants;Rejuvenation;Risk Factors;Role;Solid;Stereotyping;synuclein;synucleinopathy;System;therapeutic target;transcriptomics;transmission process;uptake

PROJECT_TITLE: Heterochronic Blood Exchange Inhibits α?Synucleinopathy through Modulating Plasma Protein's Mediation on Pathological α?Synuclein Spreading


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Narrative/Public Health Relevance: Vascular diseases combined account for half the morbidity and mortality in the United States and throughout the world. New single cell data is available for vascular cells throughout the body, however it is not known which cell populations contribute to vascular dysfunction and disease progression. We will build and share new computational software to integrate data from genetic association studies and single cell analysis of diseased vascular tissue to identify the genes, pathways and cell types that contribute to risk of multiple common diseases.

PI_NAMEs: GUPTA, RAJAT M (contact);SEGRE, AYELLET VERED

PROGRAM_OFFICER_NAME: CHARETTE, MARC F

PROJECT_TERMS: Affect;angiogenesis;Aorta;Aortic Aneurysm;autoencoder;Biological Process;Biology;Blood Vessels;Cell Physiology;cell type;Cells;Clinical;Collection;Communities;Complex;Computational Biology;Computer software;Computing Methodologies;Coronary Arteriosclerosis;Data;data integration;Data Set;data sharing;Dementia;Diabetes Mellitus;Disease;Disease Progression;Disease susceptibility;disorder risk;Effect Modifiers (Epidemiology);Endothelial Cells;Ensure;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic association;genetic information;Genetic Markers;Genetic Risk;Genetic Transcription;genome wide association study;genomic data;genomic profiles;Genotype;Heterogeneity;Human;Human BioMolecular Atlas Program;Human body;human data;human tissue;Integrins;Laboratories;Link;Lipids;Location;Malignant Neoplasms;Methodology;Methods;Morbidity - disease rate;mortality;multiple data types;Mus;Myofibroblast;Normal Cell;novel;open data;Organ;Pathogenicity;Pathway interactions;Play;Population;Process;programs;public health relevance;Research Personnel;Risk;Role;Sampling;sex;Signal Transduction;single cell analysis;single nucleus RNA-sequencing;single-cell RNA sequencing;Smooth Muscle Myocytes;Source;Stroke;System;Temporal Arteritis;Tissues;trait;United States;Vascular Diseases;Vascular Smooth Muscle;Work

PROJECT_TITLE: Identifying the organotypic and disease-specific vascular cell populations by integrating single cell data with polygenic risk


ORG_CITY: Chicago

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: PROJECT NARRATIVE The R35 proposal will develop ultrasensitive quantification tools to characterize cytokine release from the plasma membrane. Using T cells and interleukin-2 as a model system, the research will probe the temporal and directional cytokine release profiles, proximity-based membrane regulation, and the distribution between soluble and extracellular-vesicle-associated cytokines during T cell activation. The research program will enhance the fundamental understanding of the cytokine release at the molecular level and enable the search for membrane mechanisms to modulate the process.

PI_NAMEs: HU, YING SAMUEL (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Acute;Area;Biological Assay;Biological Models;Calcium Channel;Cell Communication;Cell membrane;Cells;clinical translation;Clinical Trials;Complex;cytokine;cytokine release syndrome;Disease;Drug Targeting;Enzyme-Linked Immunosorbent Assay;Event;extracellular vesicles;FDA approved;Flow Cytometry;Future;Immune;immune imaging;Impaired wound healing;inhibitor;Interleukin-2;Investigation;Ion Channel;Life;Masks;Membrane;Molecular;nanoscale;novel;Phenotype;Process;programs;Regulation;Research;Resolution;screening;Signaling Protein;Site;T-Cell Activation;T-Lymphocyte;Techniques;Technology;Time;tool;Vesicle

PROJECT_TITLE: Ultrasensitive quantification of cytokine release from T cells


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Hearing Loss;Neurosciences;Rehabilitation

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Project Narrative: With the growth of the United States’ aging population, acquired deafness is becoming increasingly common, and many individuals suffer hearing loss severe enough to warrant cochlear implantation. Enormous speech recognition outcome variability exists in adult cochlear implant (CI) users, which is only partly explained by clinical measures, and this unexplained variability impedes our ability to predict postoperative outcomes, identify sources of poor outcomes, and tailor rehabilitation protocols for individuals. This project will determine how a comprehensive approach including “bottom-up” sensory and “top-down” cognitive-linguistic factors predicts CI outcomes after implantation.

PI_NAMEs: MOBERLY, AARON C (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Acquired Deafness;Action Potentials;Address;Adult;Age;aging population;Audiology;Auditory Psychophysics;Clinical;clinical predictors;Cochlear implant procedure;Cochlear Implants;Cognitive;design;Devices;Electrocochleographies;Electrodes;experience;Face;Future;Goals;Growth;hearing impairment;Image;implantation;Implanted Electrodes;improved;Individual;Individual Differences;Knowledge;lexical;lexical processing;Linguistics;Measures;Modeling;Nerve;non-verbal;Operative Surgical Procedures;Outcome;Patients;Perceptual learning;Performance;phonology;Postoperative Period;Predictive Factor;Process;processing speed;prognostication;Protocols documentation;rehabilitation strategy;Rehabilitation therapy;Research;Research Project Grants;scaffold;Scientist;semantic processing;Semantics;Sensorineural Hearing Loss;Sensory;Sensory Process;Severities;Short-Term Memory;skills;Source;Speech;speech recognition;standard of care;Surgeon;Time;United States;Verbal Learning;Visual;X-Ray Computed Tomography

PROJECT_TITLE: Predicting Speech Recognition in Adults Receiving Cochlear Implants

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


NIH_SPENDING_CATS: Aging;Cerebrovascular;Neurosciences

ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

PHR: The work described in this proposal is based on experiments demonstrating that GDF11, an endogenous blood factor, can improve brain function by regulating properties of its vasculature. These studies will investigate molecular changes that take place in vasculature located in neurogenic and non-neurogenic regions, both of which are likely to impact the health of neurons and glial cells. In addition, the actions of systemically administered GDF11 will be compared with those of GDF11 expressed by hippocampal cells.

PI_NAMEs: RUBIN, LEE L (contact)

PROGRAM_OFFICER_NAME: NEWMAN, ELIZABETH

PROJECT_TERMS: Adult;adult neurogenesis;Affect;Aging;aging brain;Alzheimer's Disease;American;angiogenesis;Astrocytes;Blood;Blood - brain barrier anatomy;Blood Vessels;Brain;brain cell;brain endothelial cell;Brain region;Cardiovascular system;Cell Physiology;Cell secretion;cell type;Cells;Central Nervous System;Cerebrovascular system;Cognition;Data;Development;Disease;experimental study;Family;Future;GDF11 gene;GDF8 gene;Gene Expression;Genetic;Genetic Transcription;Health;Health Care Costs;Heterogeneity;Hippocampus;Histologic;Histology;Impaired cognition;improved;In Vitro;Injections;Ligands;Measures;Methods;Modification;Molecular;Mus;nerve stem cell;neural;Neurodegenerative Disorders;neurogenesis;Neuroglia;neuronal survival;Neurons;Neurophysiology - biologic function;old mice;older adult;Operative Surgical Procedures;Parkinson Disease;Positioning Attribute;Production;Property;Publishing;receptor;Recovery;Serum Proteins;Signal Pathway;Signal Transduction;Structure;Testing;Therapeutic;therapeutically effective;Transcriptional Regulation;transcriptome sequencing;transcriptomics;Transforming Growth Factor beta;Transgenic Mice;Vascular Dementia;Vascular Endothelial Growth Factors;Work;young adult

PROJECT_TITLE: Direct and Indirect Effects of GDF11 in the Aging Central Nervous System


ORG_DEPT: BIOLOGY

ORG_NAME: NEW YORK UNIVERSITY

PHR: PROJECT NARRATIVE Variable transcription factor-DNA interaction mediates phenotypic variation, including traits and a wide range of human diseases. Our proposed studies aim to understand how naturally occurring genetic and epigenetic variation in the genome gives rise to variation in transcription factor-DNA interactions, and how this variation collectively alters the regulatory networks in the cell. Our research will have the potential to reveal novel principles for predicting the regulatory functions of genetic and epigenetic variants, a critical element in the development of precision medicine.

PI_NAMEs: HUANG, SHAO-SHAN CAROL (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Address;Affect;base;Binding;Binding Sites;Catalogs;Cells;Code;Collection;Computer Analysis;Computer Models;Development;DNA;Elements;empowerment;Environment;Epigenetic Process;epigenetic variation;epigenome;epigenomics;Experimental Models;Family;Gene Expression;Genes;Genetic;Genetic Variation;Genome;genome-wide;Genomic DNA;Goals;human disease;Knowledge;Link;Location;Maps;Mediating;Modification;Molecular;Mouse-ear Cress;novel;Pattern;Phenotype;phenotypic data;Play;precision medicine;programs;protein protein interaction;reference genome;Research;Resolution;Role;Shapes;Specificity;trait;transcription factor;Variant

PROJECT_TITLE: Dissecting natural variation in transcription factor - DNA interactions


ADMINISTERING_IC: HD

ED_INST_TYPE: GRADUATE SCHOOLS

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

NIH_SPENDING_CATS: Adolescent Sexual Activity;Basic Behavioral and Social Science;Behavioral and Social Science;Child Abuse and Neglect Research;Contraception/Reproduction;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Prevention;Social Determinants of Health;Teenage Pregnancy;Violence Research;Youth Violence

ORG_CITY: Boulder

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Project Narrative This project will provide critical information on contraceptive access and use and factors that promote sexual and reproductive health among youth with child welfare involvement – a vastly understudied topic and population. The study will use secondary data from a multi-wave survey of youth, between the ages 12 and 18 with child welfare involvement, to provide basic information on contraceptive access and use across adolescence, identify modifiable factors that promote reproductive agency and autonomy, and clarify differences by demographic and child welfare characteristics – key factors for service delivery in child welfare settings.

PI_NAMEs: COMBS, KATIE MASSEY (contact)

PROGRAM_OFFICER_NAME: POPKIN, RONNA

PROJECT_TERMS: Adolescence;Adolescent;Adult;adverse childhood events;African American;Age;American Indians;Attitude to Health;biological sex;Buffers;career;Categories;Characteristics;Child;Child Abuse and Neglect;child protective service;Child Welfare;Code;Collection;Communities;Contraceptive Agents;Contraceptive Usage;Data;Education;Ethnic Origin;Ethnic Population;experience;Face;Family;Female;Female Adolescents;foster care;Future;General Population;Health behavior;high school;Home;Intervention;Interview;Investigation;Knowledge;Longitudinal Studies;male;marginalization;Modeling;multilevel analysis;Outcome;Participant;participant interview;Personal Satisfaction;Persons;Policy Maker;Population;Predictive Factor;Pregnancy;Pregnancy in Adolescence;Prevalence;Prevention;Preventive;psychosocial;Race;racial population;Reporting;reproductive;Research;Research Personnel;response;Risk;Risk Factors;Role;Sampling;Schools;service delivery;Services;sex;sexual and reproductive health;Social support;socioeconomics;Source;Surveys;System;Testing;unintended pregnancy;Vulnerable Populations;Youth

PROJECT_TITLE: Examining Contraceptive Access and Use among Youth with Child Welfare Involvement

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Population Sciences Study Section[CHHD-W]


ADMINISTERING_IC: AI

ED_INST_TYPE: OVERALL MEDICAL

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The development of curative approaches for HIV infection is now recognized as both a necessary and attainable goal. Hematopoietic stem cell transplantation resulting in a CCR5-deficient immune system has been shown to functionally cure HIV infection in two separate patients, but such an approach is not scalable to the general population. We propose here to develop novel AAV vectors targeted to immune system cells to support delivery of therapeutics such as HIV-targeted CRISPR-Cas9, chimeric antigen receptors, broadly neutralizing antibodies, or CCR5-blocking antibodies to mimic a CCR5-deficient immune system.

PI_NAMEs: ASOKAN, ARAVIND ;SACHA, JONAH B. (contact)

PROGRAM_OFFICER_NAME: POON, BETTY

PROJECT_TERMS: adeno-associated viral vector;Allogenic;Animal Model;Antibodies;antiretroviral therapy;B-Lymphocytes;Bar Codes;Berlin;Binding;Blocking Antibodies;Capsid;CCR5 gene;cell type;Cells;chimeric antigen receptor;clinical development;clinical translation;Clinical Trials;clinically relevant;cohort;Coupled;CRISPR/Cas technology;delivery vehicle;Dependovirus;design;Development;Directed Molecular Evolution;Disease remission;Dose;Engineering;Ensure;Epidemic;Evolution;extracellular;Future;Gene Delivery;gene therapy;Gene Transduction Agent;General Population;global health;Goals;Health Priorities;Hematopoietic Stem Cell Transplantation;HIV;HIV Infections;Human;human disease;Immune;Immune system;immunodeficiency;improved;in vivo;Individual;inhibitor;interest;Intramuscular;Intravenous;Knowledge;leukemia;Libraries;London;Macaca;Macaca mulatta;Mediating;Modality;Molecular Cloning;Monitor;Muscle Cells;neutralizing antibody;novel;Patients;Persons;pharmacologic;Phenocopy;Phenotype;Plasma;pre-clinical;Property;purge;Recording of previous events;Rectum;Role;Safety;simian human immunodeficiency virus;small molecule;Specificity;Stem cell transplant;Structure;T-Lymphocyte;Techniques;Technology;Testing;Therapeutic;therapeutically effective;Time;Tissues;Variant;Viral;viral rebound;Viral reservoir;Virus Replication;Work

PROJECT_TITLE: Evolving Novel AAV Vectors for Gene Therapy to Cure HIV


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

PHR: This project is focused on advancing non-viral transposon-based genome engineering. The proposed strategy will advance genome engineering of human cells, in vivo in animal models, and enable site-directed genomic integration. The studies and results will have broad impact for biotechnology and therapeutic applications.

PI_NAMEs: WILSON, MATTHEW H (contact)

PROGRAM_OFFICER_NAME: DARINGER, NICHOLE MARIE

PROJECT_TERMS: Advanced Development;Affect;Animal Model;Biological Assay;Biotechnology;Cell Line;Cell Therapy;Cells;Clinical Trials;clinically relevant;Communication;Complex;cost;Development;DNA;DNA Integration;DNA Transposons;Embryo;Engineering;Enzymes;flexibility;functional genomics;Gene Delivery;gene delivery system;gene discovery;gene therapy;Gene Transfer;Genome;Genome engineering;Genomics;genotoxicity;Human;Human Engineering;Human Genome;Hybrids;immunogenicity;In Vitro;in vivo;induced pluripotent stem cell;Injections;integration site;Inverted Terminal Repeat;Kidney;Liver;mammalian genome;Mediating;Methodology;Modification;Mus;Nature;next generation;next generation sequencing;non-viral gene delivery;novel strategies;Oncogenes;Organ;Paste substance;Plasmids;Post-Translational Protein Processing;Production;Protein Binding Domain;Protein-Protein Interaction Map;Proteins;Publishing;Recombinant Proteins;repaired;Reporter;Site;stable cell line;success;System;T cell therapy;T-Lymphocyte;Testing;Therapeutic;therapeutic transgene;three dimensional structure;Transfection;transgene expression;Transgenic Animals;Transgenic Mice;Transposase;vector genome;Viral

PROJECT_TITLE: Next generation transposon vectors for genome engineering

STUDY_SECTION: GDD

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


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;HIV/AIDS;Infectious Diseases;Mental Health;Prevention

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

PHR: PROJECT NARRATIVE For people with HIV who have cancer, consistent engagement in HIV care is integral to successful cancer treatment, but the evidence base for integrating HIV care into cancer care in resource-constrained settings like Zimbabwe is limited. New strategies to support continuous engagement in HIV care during cancer treatment in tertiary care settings in Zimbabwe are needed. The proposed work addresses this critical gap by identifying barriers to HIV care engagement during cancer treatment, and developing, refining, and testing strategies to address those barriers.

PI_NAMEs: MONTANO, MICHALINA  (contact)

PROGRAM_OFFICER_NAME: POLLARD-BRANCHARD, SUZANNE LEE

PROJECT_TERMS: Address;AIDS related cancer;antiretroviral therapy;Cancer Burden;cancer care;Cancer Center;cancer diagnosis;Cancer Hospital;Cancer Patient;cancer prevention;cancer therapy;career development;Caring;Clinical;clinical care;Clinical Data;cohort;comorbidity;Consolidated Framework for Implementation Research;Continuity of Patient Care;Data;design;Development;Development Plans;Disease;Documentation;Dose;effectiveness/implementation trial;Essential worker;Evaluation;evidence base;evidence based guidelines;experience;Face;global health;Goals;Health Resources;Healthcare;Healthcare Systems;HIV;Hospitals;implementation framework;implementation science;improved outcome;Income;integrated care;Interruption;Intervention;Interview;Malawi;Malignant Neoplasms;Measures;Mentors;Methodology;Methods;Morbidity - disease rate;mortality;multi-component intervention;novel strategies;Observational epidemiology;Oncology;Outcome;Participant;participant enrollment;Pathway interactions;Patients;Persons;Prevalence;primary care setting;primary outcome;process improvement;programs;Provider;Qualitative Methods;Quasi-experiment;Questionnaires;Recommendation;Regional Cancer;Reporting;Research;research clinical testing;Research Design;Research Methodology;Research Personnel;Resource-limited setting;Resources;scale up;screening;Screening for cancer;secondary outcome;Services;South Africa;Southern Africa;Subgroup;Techniques;tertiary care;Testing;therapy design;Time;time use;Training;treatment center;treatment guidelines;Treatment outcome;Uganda;United States;uptake;Visit;Work;Zimbabwe

PROJECT_TITLE: Development and Testing of a Multi-Component Intervention to Support HIV Care Engagement among Patients Receiving Cancer Treatment in Zimbabwe

STUDY_SECTION: PPAH

STUDY_SECTION_NAME: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH]


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

ORG_CITY: TAMPA

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

PHR: PROJECT NARRATIVE Discovering unique epigenetic targets in the human malaria parasite Plasmodium falciparum with function and structure diverse from those in the human host is critical for developing novel interventions in malaria control. Based on previous studies and our preliminary data, we propose to define the function and substrates of PfSET7, a SET-domain containing lysine methyltransferase with unique structures and functions in two pivotal blood stages: merozoite for invasion and gametocyte for transmission. With the completion of this project, we will reveal the unique function and specificity of PfSET7 in P. falciparum and will lay a solid foundation for the development of novel apicomplexan-specific epigenetic drugs.

PI_NAMEs: MIAO, JUN  (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Apical;Artemisinins;asexual;Biological Assay;Biology;Biomedical Research;Blood;cancer therapy;Catalysis;Cell Nucleus;Cessation of life;Chromatin;Combined Modality Therapy;Complex;conditional knockout;CRISPR interference;Cytoplasm;Cytosol;Data;Defect;Development;Down-Regulation;Drug Targeting;Enzymes;epigenetic drug;Epigenetic Process;Essential Genes;Face;Falciparum Malaria;Family;Foundations;Future;Gene Expression;genetic manipulation;Goals;Guide RNA;histone methylation;Histone-Lysine N-Methyltransferase;Histones;Human;human disease;Immunoprecipitation;Impairment;In Vitro;inhibitor;insight;Intervention;Invaded;knock-down;Knock-out;knockout gene;Lysine;Malaria;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Methylation;methylome;Methyltransferase;model organism;Motility;new technology;new therapeutic target;non-histone protein;novel;overexpression;Parasite resistance;Parasites;Pharmaceutical Preparations;Phenotype;Plasmodium;Plasmodium falciparum;Process;Proteins;Proteomics;Regulation;SET Domain;Set protein;Sexual Development;Site;Solid;Specificity;Structure;Substrate Specificity;System;Theileria;Therapeutic;therapeutic development;Toxoplasma gondii;transcriptome sequencing;transcriptomics;transmission process;Virulent

PROJECT_TITLE: Malaria parasite harbors a unique protein lysine methyltransferase targeting both chromatin and motility machinery

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Project Narrative Physician-scientists perform a critical role at the interface between biomedical research and clinical medicine. This program will train a diverse group of students with outstanding potential and prepare them to enter the biomedical research workforce as research active, physician-scientists. Informed by their knowledge of science and clinical medicine, they will perform basic, translational, and clinical research that leads to new approaches to prevent, treat, or cure disease and improve the health of Americans and people around the world.

PI_NAMEs: AKABAS, MYLES H. (contact)

PROGRAM_OFFICER_NAME: AIYEGBO, MOHAMMED S

PROJECT_TERMS: Medical;Scientist;Training Programs

PROJECT_TITLE: Medical Scientist Training Program

STUDY_SECTION: TWD

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: SAINT LOUIS

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Ischemic stroke is the leading cause of long-term disability in the United States and places an enormous financial burden. The brain has some intrinsic capacity for repair, but our understanding of the repair mechanisms remains very limited. The proposed TPM-PAM technique holds the potential to offer new insights into the spatiotemporal coordination of post-stroke neural and vascular repair, as well as the underlying metabolic requirements, which may reveal promising new therapeutic targets to enhance functional recovery.

PI_NAMEs: HU, SONG  (contact);LEE, JIN-MOO ;YANG, LAN

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Acoustics;Acute;acute stroke;Adverse effects;angiogenesis;Animals;awake;Behavioral;Benchmarking;Blood;Blood capillaries;Blood flow;Blood Vessels;Brain;Brain imaging;Brain Injuries;brain repair;burden of illness;Cephalic;cerebrovascular;Cerebrum;cognitive function;Collection;Computer software;cost;Coupling;Data;design;Detection;Development;Event;Facilities and Administrative Costs;Financial Hardship;Fluorescence;Fluorescence Microscopy;genetic manipulation;hemodynamics;Image;Imaging Techniques;Impairment;improved;improved outcome;in vivo;Individual;Infarction;Injury;insight;intravital imaging;Ischemic Stroke;Knockout Mice;Life Expectancy;Light;light transmission;Long term disability;Maps;Medical Care Costs;Metabolic;Metabolism;Microscopic;microscopic imaging;Microscopy;Modality;model organism;Molecular;Motor;Mus;neural;neural circuit;neural repair;neuronal circuitry;Neurons;neurovascular;neurovascular coupling;new therapeutic target;Optics;Oxygen;Patients;Penetration;Performance;Persons;post stroke;Process;Productivity;Property;prototype;Recovery;Recovery of Function;repaired;Research;Resolution;restoration;sensor;Sensory;serial imaging;Silicon;spatiotemporal;Stroke;stroke recovery;stroke therapy;Survival Rate;Survivors;Synaptic plasticity;System;Techniques;technology development;Testing;Transducers;transmission process;two photon microscopy;two-photon;Ultrasonics;ultrasound;United States

PROJECT_TITLE: Integrating TPM and PAM to examine the metabolic underpinning of neurovascular repair after stroke


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety;Precision Medicine

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

PHR: Project Narrative  This proposal aims to develop novel statistical methods and machine learning algorithms for use on real world data sets and clinical trial data in order to infer dynamic treatment regimens. The proposal will address im- portant challenges to the integration of real world data into estimation, such as differential distributions, real world treatment patterns, confounding bias and consideration of beneﬁt-risk tradeoff. The results from this proposal will complement the current knowledge base for individual patient care and will further accelerate the translation of clinical trial ﬁndings into practice.

PI_NAMEs: WANG, YUANJIA ;ZENG, DONGLIN  (contact)

PROGRAM_OFFICER_NAME: YUAN, JEAN

PROJECT_TERMS: Academic Medical Centers;Acceleration;Achievement;Address;Adherence;Adverse event;Affect;algorithm development;Algorithms;American;Atherosclerosis;Benefits and Risks;cardiovascular disorder risk;Center for Translational Science Activities;Chronic Kidney Failure;clinical decision-making;clinical practice;Clinical Trials;cohort;comorbidity;Complement;Computer software;cost efficient;Data;data modeling;Data Set;Databases;Decision Making;Diabetes Mellitus;Dimensions;Disadvantaged;Disease;disease registry;Effectiveness;efficacy outcomes;Electronic Health Record;Ensure;Epidemic;Equilibrium;Exclusion;feature selection;Feedback;Funding;Goals;Guidelines;Health Status;Hypoglycemia;improved;Individual;individual patient;individualized medicine;Inequality;insight;Joints;knowledge base;Lead;Learning;learning algorithm;learning strategy;Length;machine learning algorithm;machine learning method;Maintenance;Managed Care;Medical;Medical center;method development;Methods;Modeling;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Observational Study;Ohio;optimal treatments;Outcome;Patient Care;patient oriented;patient population;Patient Preferences;Patients;Pattern;Performance;personalized care;personalized decision;Population;Population Distributions;Population Heterogeneity;precision medicine;preference;Procedures;Process;prospective;Public Health;Quality Control;Randomized, Controlled Trials;Recommendation;Risk;Safety;Sample Size;Sampling;Selection Bias;semiparametric;side effect;simulation;social health determinants;software development;statistical and machine learning;statistical learning;Statistical Methods;Surveys;theories;Time;tool;translational clinical trial;treatment choice;treatment effect;treatment guidelines;treatment pattern;Treatment Protocols;treatment strategy;Uncertainty;Universities;Update

PROJECT_TITLE: Statistical and Machine Learning Methods to Improve Dynamic Treatment Regimens Estimation Using Real World Data.

STUDY_SECTION: ASPB

STUDY_SECTION_NAME: Analytics and Statistics for Population Research Panel B Study Section[ASPB]


PHR: PROJECT RELEVANCE / NARRATIVE This research is highly relevant to public health because the organism under study causes serious human illness for which current therapies are not adequate. Effective antifungal drugs target ergosterol (the yeast equivalent of cholesterol), but nothing is known about how Cryptococcus neoformans moves this lipid within the cell to regulate its levels at the surface. Filling this gap in knowledge may advance treatment of cryptococcal infection. This work will also contribute to basic science knowledge, which will provide insights into other pathogenic fungi and areas of biology.

PI_NAMEs: DOERING, TAMARA L (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Amphotericin B;anti-fungal agents;Area;Back;Basic Science;Binding;Biological Assay;Biology;Carrier Proteins;Cell membrane;Cells;Cessation of life;Cholesterol;clinical application;Columbidae;Cryptococcus;Cryptococcus neoformans;Dangerousness;Defect;Developing Countries;DNA Sequence Alteration;DNA sequencing;Drug Interactions;Drug Targeting;Endoplasmic Reticulum;Engineering;Equilibrium;Ergosterol;Exhibits;experience;experimental study;Family;Fluorescence-Activated Cell Sorting;Fungal Components;fungus;Future;gene discovery;Genes;genetic approach;Genetic Risk;Genetic Screening;Genome;genome-wide;Genomic approach;Genomics;Glycosphingolipids;Goals;Growth;Hand;HIV;Homologous Gene;Human;improved outcome;Individual;Infection;insight;interest;Investigation;Knowledge;Label;lipid transport;Lipids;Lung;Measures;Mediating;member;Membrane;Membrane Fluidity;Methods;Morbidity - disease rate;Morphology;Movement;mutant;Mutation;novel;Organelles;Organism;pathogen;Pathogenesis;pathogenic fungus;patient population;Phospholipids;polypeptide;Population;Positioning Attribute;prevent;Process;Productivity;Protein Family;protein function;Proteins;Public Health;Research;Resistance;Saccharomyces cerevisiae;skills;Sterols;Stress;Structure;success;Surface;System;Therapeutic;Toxic effect;vesicle transport;Virulence;whole genome;Work;Yeast Model System;Yeasts

PROJECT_TITLE: Leveraging genomic approaches to define sterol transport in Cryptococcus neoformans


ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

PHR: PROJECT NARRATIVE Redox imbalance, characterized by high reactive oxygen species (ROS) and low reactive nitrogen species (RNS), is a fundamental mechanism of endothelial cell (EC) dysfunction contributing to the inflammatory vascular and metabolic diseases such as atherosclerosis, diabetes and peripheral arterial disease. Our preliminary evidence suggests that EC metabolism and ROS are intimately connected and involved in vascular disease. The proposed studies will identify key mechanisms dictating the interplay of metabolism with ROS/NO and how this impacts endothelial function, which will lead to new therapeutic strategies.

PI_NAMEs: FUKAI, TOHRU  (contact);USHIO-FUKAI, MASUKO

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: Acceleration;Address;Adhesions;aerobic glycolysis;Affect;angiogenesis;Animals;Aorta;Atherosclerosis;Biological;Biological Assay;Biological Availability;Blood Pressure;Blood Vessels;cardiometabolism;Cardiovascular Diseases;Cell Adhesion Molecules;Cell model;cell motility;Cell Physiology;Cells;Cellular Metabolic Process;chemokine;Chronic;Complex;Consumption;Copper;CRISPR/Cas technology;Cyclic GMP;cytokine;Data;Dedications;Development;Diabetes Mellitus;diabetic;dihydroethidium;disease model;effective therapy;Endothelial Cells;endothelial dysfunction;Endothelium;Engineering;Enzymes;Epigenetic Process;Equilibrium;Event;experience;extracellular;Fluorescence;Functional disorder;Gene Expression Profiling;Genes;Genus Hippocampus;Glycolysis;Goals;Histologic;Hormonal;Hydrogen Peroxide;Hypertension;Impairment;improved;in vivo;Individual;Inflammation;Inflammatory;innovation;Intervention;Investigation;Knock-in;Knock-in Mouse;Knowledge;Label;Leptin;leptin receptor;Link;LoxP-flanked allele;Measurement;Measures;Mesenchymal;Metabolic;Metabolic Diseases;Metabolic Pathway;Metabolism;metabolomics;Mitochondria;Modeling;Molecular;monocyte;Morbidity - disease rate;mortality;mouse model;Mus;Mutant Strains Mice;Nitric Oxide;novel;novel therapeutic intervention;Obesity;Oxidation-Reduction;Oxidative Stress;Pathway interactions;Peripheral arterial disease;Permeability;Phenotype;Phosphotransferases;Plasmids;Process;programs;Proliferating;Protein Dynamics;Reactive Nitrogen Species;Reactive Oxygen Species;Reagent;Relaxation;Risk Factors;RNA metabolism;Severities;sex;Shapes;Signal Transduction;single-cell RNA sequencing;SLC2A1 gene;Stains;success;synergism;Telemetry;Testing;tetrahydrobiopterin;Thrombosis;transgene expression;Tube;vascular bed;Vascular Diseases;vasoconstriction;Vasodilation;Viral;Warburg Effect

PROJECT_TITLE: Endothelial Metabolism and Redox Imbalance in Vascular Disease

STUDY_SECTION: HLBP

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


PI_NAMEs: FUKAI, TOHRU  (contact)

PROJECT_TERMS: Accounting;Budgets;Collaborations;Computers;Consultations;Data;Endothelium;Ensure;Expenditure;Experimental Designs;Goals;Grant;Human Resources;Individual;Institution;Laboratories;meetings;Metabolism;Occupational activity of managing finances;operation;organizational structure;Oxidation-Reduction;Program Research Project Grants;Program Reviews;programs;Research;Research Personnel;Research Project Grants;Sample Size;scientific organization;Scientist;Statistical Data Interpretation;synergism;Universities;Vascular Diseases;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Genetics

PI_NAMEs: STEPP, DAVID W (contact)

PROJECT_TERMS: Anatomy;Animal Experimentation;Animal Model;Animals;Area;Autopsy;Award;Biological Assay;Blood Vessels;Body Composition;Breeding;cardiometabolism;Cells;Collaborations;Confounding Factors (Epidemiology);Data;Data Analyses;Data Science;Data Set;Development;Endothelial Cells;Endothelium;Evaluation;experience;experimental study;Fatty acid glycerol esters;Feedback;Foundations;Generations;Genes;Glucose;Growth;Heart Rate;In Vitro;in vivo;Individual;International;Lipids;meetings;member;Metabolic;Metabolic Diseases;metabolic phenotype;Metabolism;Methodology;Microanatomy;Modeling;Molecular;Monitor;Morphologic artifacts;mouse model;Mus;Myography;next generation;novel;operation;Output;Oxidation-Reduction;Oxygen Consumption;Participant;Phenotype;Physiology;Plasma;Play;pressure;prevent;programs;Proteins;Protocols documentation;Publishing;Quality Control;Reagent;Reporting;Reproducibility;Research;Resolution;Resources;Role;Services;Solid;Standardization;Structure;synergism;System;Tamoxifen;Techniques;Technology;Tissues;Vascular Diseases;Work

PROJECT_TITLE: Animal and Metabolic Phenotype Analytic Core


NIH_SPENDING_CATS: Biotechnology;Genetics

PI_NAMEs: LUCAS, RUDOLF  (contact)

PROJECT_TERMS: Animals;Binding;Bioinformatics;Calibration;CDH5 gene;Cell Adhesion Molecules;Cell Culture Techniques;Cell Separation;Cells;Cellular Metabolic Process;chemokine;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Consumption;cost;CRISPR/Cas technology;cytokine;Data Analyses;data dissemination;Dependovirus;Diabetes Mellitus;Doctor of Philosophy;E-Selectin;electric impedance;Electrodes;Endothelial Cells;Endothelium;Enzyme-Linked Immunosorbent Assay;Equipment;extracellular;Film;fluorescein isothiocyanate dextran;fluorescence microscope;Fostering;Gene Deletion;Gene Delivery;Gene Expression;Generations;Genes;Genetic;genetic manipulation;Genomics;Genus Hippocampus;Glucose;Glutamine;Glycolysis;Goals;Gold;Human;human tissue;Hydrogen Peroxide;Image;In Vitro;Inflammation;Inflammatory;Institution;Insulin-Dependent Diabetes Mellitus;Intercellular adhesion molecule 1;Knock-out;Label;Laboratories;Lentivirus;Leptin;Letters;Leukocytes;magnetic beads;Mass Spectrum Analysis;Measurement;Measures;Mesenchymal;Metabolism;metabolomics;Methods;Mitochondria;monocyte;monolayer;Mus;Nitrogen;nitrosative stress;Obesity;Operative Surgical Procedures;Outcome;Oxidation-Reduction;Oxidative Stress;Oxygen;P-Selectin;Pathogenicity;Patients;PECAM1 gene;Permeability;Phenotype;Plasma;Post-Translational Protein Processing;programs;Proteomics;Protocols documentation;PTPRC gene;recombinant adenovirus;Research Personnel;Research Project Grants;Sampling;Services;single-cell RNA sequencing;Small Interfering RNA;Standardization;Suspensions;synergism;System;Technology;Tissues;TNF gene;tool;Tracer;transcriptomics;Transfection;Transgenic Mice;Vascular Cell Adhesion Molecule-1;Vascular Diseases;Viral;VWF gene

PROJECT_TITLE: Endothelial Cell Analytic Core


PROJECT_TERMS: Acceleration;Address;Adenoviruses;aerobic glycolysis;angiogenesis;Aorta;Apolipoprotein E;Arterial Fatty Streak;ATAC-seq;atherogenesis;Atherosclerosis;ATP phosphohydrolase;Biological Availability;Biosensor;Cardiovascular Diseases;cardiovascular risk factor;catalase;Cell Lineage;Cell Physiology;Cell Separation;Cells;Cellular Metabolic Process;Chelating Agents;chelation;cofactor;Copper;CRISPR/Cas technology;cytokine;Cytosol;Data;Diabetes Mellitus;dietary;Endothelial Cells;endothelial dysfunction;Endothelium;Enzymes;Epigenetic Process;Equilibrium;experimental study;Exposure to;Fluorescence Microscopy;Functional disorder;Genetic;Glycolysis;Glycolysis Inhibition;Goals;High Fat Diet;histone demethylase;Human;in vivo;Inductively Coupled Plasma Mass Spectrometry;Inflammation;Inflammatory;innovation;insight;Intake;knock-down;Knock-in;Knock-in Mouse;Ligation;Link;loss of function;Measures;Mediating;Mesenchymal;metabolic phenotype;Metabolism;metabolomics;Micronutrients;Mitochondria;Modeling;Molecular;Morbidity - disease rate;mortality;Mus;mutant;Mutant Strains Mice;novel;novel therapeutic intervention;Oxidation-Reduction;Oxidative Stress;Permeability;Phenotype;Play;Reporter;Reporting;response;Roentgen Rays;Role;Shapes;single-cell RNA sequencing;Snails;Source;Synchrotrons;Testing;Tissues;transcription factor;transcriptome sequencing;transcriptomics;Up-Regulation;Vascular Diseases;X-Ray Emission Spectrometry

PROJECT_TITLE: Role of Cu Transporter in EC Metabolism, ROS, and Atherosclerosis


NIH_SPENDING_CATS: Autoimmune Disease;Cardiovascular;Diabetes;Pediatric;Women's Health Research

PI_NAMEs: BELIN DE CHANTEMELE, ERIC J (contact)

PROJECT_TERMS: 6-Phosphofructo-2-kinase;adipokines;Aorta;Arteries;Atherosclerosis;Bioenergetics;Blood Vessels;Cardiovascular Diseases;Cardiovascular system;Cell Physiology;cell type;Cells;Cellular Metabolic Process;cellular transduction;Chromosomes;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Complications of Diabetes Mellitus;Coronary heart disease;Cytoprotection;Data;Diabetic Angiopathies;Diabetic macrovascular disease;Disabling;early onset;Endothelial Cells;endothelial dysfunction;Endothelium;environmental stressor;Enzymes;Equilibrium;Event;expectation;Exposure to;Female;flexibility;Four Core Genotypes;Fructose-2,6-bisphosphatase;Genetic;genetic approach;Glycolysis;Goals;Gonadal Steroid Hormones;Homeostasis;Housekeeping;Impairment;Individual;Insulin-Dependent Diabetes Mellitus;Knock-in Mouse;Leptin;Life;male;Mediating;Metabolism;Molecular;mouse model;Mus;NADPH Oxidase 1;Nitric Oxide;novel;Organelles;Oxidation-Reduction;Oxidative Stress;Pathologic;Pathway interactions;pharmacologic;Physiological;Play;Premenopause;prevent;Production;programs;protective effect;Reactive Oxygen Species;Regulation;Relaxation;response;Role;sex;Sex Chromosomes;Shapes;Signal Transduction;Source;Testing;Up-Regulation;Vascular Diseases;Vasodilation;vasomotion;Woman;women patients;Women's Role

PROJECT_TITLE: Sex and Leptin control of endothelial cell glycolysis and redox balance in Type 1 Diabetes


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Diabetes

PI_NAMEs: USHIO-FUKAI, MASUKO  (contact)

PROJECT_TERMS: Address;aerobic glycolysis;AMP-activated protein kinase kinase;angiogenesis;Animal Model;Automobile Driving;Biological Assay;Biosensor;C-terminal;cardiovascular risk factor;catalase;Cellular Metabolic Process;CRISPR/Cas technology;cysteinesulfenic acid;Cytosol;Data;Diabetes Mellitus;diabetic;disease model;disulfide bond;Endothelial Cells;Endothelium;Enzymes;Event;Gene Transfer;genome editing;Glucose;Glycolysis;Goals;Guanosine Triphosphate Phosphohydrolases;Hindlimb;Hydrogen Peroxide;Impairment;In Situ;in vivo;innovation;insight;Insulin-Dependent Diabetes Mellitus;Ischemia;KDR gene;Knock-in;Knock-in Mouse;Label;Link;Measures;Metabolic;Metabolism;metabolomics;Mitochondria;Mus;Muscle;mutant;Mutant Strains Mice;Mutate;NADPH Oxidase;neovascularization;non-diabetic;novel;overexpression;oxidation;Oxidation-Reduction;Oxidative Phosphorylation;Peripheral arterial disease;Phase;Physiological;Post-Translational Protein Processing;prevent;Production;Protein Dynamics;protein protein interaction;Proteins;Proteomics;Reactive Oxygen Species;real-time images;Regulation;Reporting;Role;Signal Transduction;Signaling Molecule;Skin wound healing;Source;Structure;Therapeutic;therapeutic angiogenesis;Transgenic Mice;transmission process;treatment strategy;Vascular Diseases;Vascular Endothelial Growth Factors;Wound models

PROJECT_TITLE: Mitochondrial dynamics protein Drp1 regulation of endothelial metabolism, ROS, and ischemic vascular disease


ADMINISTERING_IC: NR

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Aging

ORG_CITY: PHILADELPHIA

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Addressing the needs of the growing population of older adults who are coping with complex health and social challenges and supporting their family caregivers are significant societal priorities. Building on our success since 2007, we will continue to prepare nurse scientists to advance science that seeks to develop and improve integrated care models, mitigate adverse social determinants of health, and equitably support older adults and caregivers throughout transitions in health (e.g., new diagnosis, illness progression) and health care (i.e., movement across health care providers or settings). Our faculty mentors will contribute rich scientific expertise, resources, and networks to provide an excellent foundation and environment for this training program.

PI_NAMEs: BOWLES, KATHRYN HELENE;NAYLOR, MARY D (contact)

PROGRAM_OFFICER_NAME: KEHL, KAREN

PROJECT_TERMS: older adult;personalized care;Risk

PROJECT_TITLE: Individualized Care for At Risk Older Adults

STUDY_SECTION_NAME: Special Emphasis Panel[ZNR1 REV-N (03)]


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

ORG_CITY: GREENSBORO

ORG_NAME: NORTH CAROLINA AGRI & TECH ST UNIV

ORG_STATE: NC

PHR: PROJECT NARRATIVE During the five-year project period, we will investigate key questions related to 1) the biochemical mechanisms underlying oxidation-induced changes in protein kinase substrate selection and 2) the functional consequences of redox modification on kinase-dependent signaling processes related to health and disease. To this end, we will build upon our recent studies, which focused on PKA-Cα and ERK2 as representative members of the AGC and MAPK kinase families, to explore the impact of redox modification on the global substrate selection of other kinase family members (including several understudied kinases in the “dark kinome”) using functional protein microarrays composed of >21,000 unique human proteins. Together, these studies will help identify points of signal integration between redox- and phosphorylation-dependent pathways while complementing existing models of pathological oxidative stress and providing new opportunities for targeted antioxidant therapeutics for many diseases (e.g., cancer, diabetes, cardiovascular disease, and several neurodegenerative disorders).

PI_NAMEs: NEWMAN, ROBERT HOWARD (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Affect;Affinity;Antioxidants;Award;Biochemical;Biophysics;Cardiovascular Diseases;Cells;Darkness;Data;Diabetes Mellitus;Diamide;Disease;Family;Family member;Health;Human;Hydrogen Peroxide;insight;interest;Malignant Neoplasms;MAPK1 gene;Mediating;member;Mentors;Minority Groups;Mitogen-Activated Protein Kinase Kinases;Mitogen-Activated Protein Kinases;Modeling;Modification;Mutation;National Institute of General Medical Sciences;Neurodegenerative Disorders;Outcome;oxidation;Oxidation-Reduction;Oxidative Stress;Pathologic;Pathologic Processes;Pathway interactions;Phosphorylation;Phosphotransferases;Physiological Processes;Post-Translational Protein Processing;preference;Process;programs;Protein Kinase;Protein Microchips;protein protein interaction;Proteins;Reactive Oxygen Species;Regulation;Research;Second Messenger Systems;Signal Pathway;Signal Transduction;spatiotemporal;Therapeutic;Underrepresented Minority

PROJECT_TITLE: Redox regulation of protein kinase function: biochemical mechanisms and cellular consequences

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


ED_INST_TYPE: HOSPITALS

FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: NARRATIVE: OVERALL Over the past 20 years, advances in the treatment of brain cancer, including glioblastoma (GBM) and medulloblastoma (MB), have been only incremental at best. The research proposed in this Brain Cancer SPORE renewal application seeks to reverse this trend by developing and testing for the first time mechanistically diverse, previously-untested therapeutic strategies that attack the highly immunosuppressive tumor microenvironment, which makes brain cancers recalcitrant to most treatments. These novel strategies include combining viro- immunotherapy with cellular therapy, targeting GBM-associated myeloid cells with small molecules, and applying immune checkpoint inhibitors and CAR T-cells to specific subsets of MB patients with hypermutant tumors.

PI_NAMEs: FUEYO, JUAN ;LANG, FREDERICK F (contact)

PROGRAM_OFFICER_NAME: HUBBARD, LEAH

PROJECT_TERMS: Activities of Daily Living;Address;Adult;Agonist;Animals;Antigen Presentation;Antigens;Award;Back;bench to bedside;Bexarotene;biobank;Bioinformatics;Biological Assay;Biological Response Modifier Therapy;Biometry;Black Populations;bone marrow mesenchymal stem cell;Brain;Brain Neoplasms;career;Cell Therapy;Cellular immunotherapy;Child;Childhood Brain Neoplasm;Childhood Malignant Brain Tumor;chimeric antigen receptor T cells;Clinic;Clinical Trials;Clinical Trials Design;Collaborations;Complementary therapies;Complex;design;Development;Diagnosis;Down-Regulation;engineered NK cell;Engineering;Epitopes;first-in-human;flexibility;Functional disorder;Funding;Genetic Engineering;Genomics;Glioblastoma;Glioma;Goals;Grant;Hispanic Populations;Home;Immune;Immune checkpoint inhibitor;immunotherapeutic virotherapy;improved outcome;Incubators;inhibitor;Malignant neoplasm of brain;Malignant neoplasm of central nervous system;Malignant Neoplasms;Mediating;Medulloblastoma;Mentors;Minority Groups;Mission;multidisciplinary;Mutation;Myelogenous;Myeloid Cells;Myeloid-derived suppressor cells;Natural Killer Cells;neuro-oncology;next generation;novel;novel strategies;oncolytic adenovirus;Oncolytic viruses;Outcome;Pathology;patient subsets;Patient-Focused Outcomes;Patients;Pediatric Hospitals;pembrolizumab;Persons;Phagocytosis;Phase;Phase I Clinical Trials;Phosphatidylinositide 3-Kinase Inhibitor;PIK3CG gene;Point Mutation;posttranscriptional;PPAR-beta;preclinical study;Preclinical Testing;Primary Neoplasm;Prognosis;programs;Records;Research;Research Personnel;Resources;Role;Science;Shapes;SHH gene;small molecule;Small Nuclear RNA;Source;targeted agent;targeted treatment;Testing;Texas;Therapeutic;Therapeutic Effect;Time;Translating;Translational Research;translational scientist;treatment strategy;trend;tumor;tumor-immune system interactions;U1 small nuclear RNA;Umbilical Cord Blood;Underrepresented Minority;Untranslated RNA;Viral;Virus;Work

PROJECT_TITLE: SPORE in Brain Cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RPRB-8 (J1)]