ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative Choroid plexus cilia are a new type of multi-sensory cilia structurally distinct from primary or motile cilia. These cilia play an important role in regulating the production of cerebrospinal fluid during development and physiology. Using advanced imaging techniques, mouse genetics and genomics, cell and molecular biology approaches, our proposed studies aim to characterize the ultrastructure of choroid plexus cilia, characterized their developmental dynamics, and elucidate the molecular basis for their regulation on cerebrospinal fluid production.

PI_NAMEs: HE, LIN  (contact)

PROJECT_TERMS: Apical;bean;Biological Process;Categories;Cells;Cellular biology;Cerebral Ventricles;Cerebrospinal Fluid;Choroid Plexus Epithelium;Cilia;ciliopathy;cilium biogenesis;Cilium Microtubule;cilium motility;Classification;Development;Electron Microscopy;Electrons;Epithelial Cells;Exhibits;extracellular;Genetic Models;Genetic Transcription;Genomics;Hydrocephalus;imaging study;Imaging Techniques;Impairment;insight;Ion Channel;Ions;kinetosome;Knockout Mice;Liquid substance;Locomotion;Mediating;Metabolic;MicroRNAs;Molecular;Molecular Biology;Molecular Target;monolayer;Motility;mouse genetics;Movement;multisensory;Mus;Mutant Strains Mice;neurodevelopment;neuron development;Nutritional;Phenotype;Physiology;Play;Production;programs;Regulation;Resolution;Role;Scanning;Scanning Electron Microscopy;Sensory;SHH gene;Signal Pathway;Signal Transduction;Site;smoothened signaling pathway;Stimulus;Structure of choroid plexus;superresolution imaging;System;Transmission Electron Microscopy;water channel

PROJECT_TITLE: Choroid Plexus Multi-Sensory Cilia Regulate Production of Cerebrospinal Fluid

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Neurosciences;Orphan Drug;Precision Medicine;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: SEATTLE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: INSTITUTE FOR SYSTEMS BIOLOGY

ORG_STATE: WA

PHR: PROJECT NARRATIVE The objective of this proposal is to use a systems approach to uncover the gene networks responsible for driving drug resistance and recurrence in an individual patient with brain cancer (glioblastoma). This capability will enable formulation of therapies that will have a higher likelihood to be effective because they will be tailored to the precise characteristics of a patient’s tumor. The research combines a hypothesis-driven approach with data- driven science to make discoveries of mechanisms underlying tumor subtype transitions –linking systems-level behavior to molecular mechanism, and bulk tumor characteristics to the behavior of single cells within a tumor.

PI_NAMEs: BALIGA, NITIN S (contact);COBBS, CHARLES S;HOTHI, PARVINDER

PROGRAM_OFFICER_NAME: COVELL, DAVID G

PROJECT_TERMS: 3' Untranslated Regions;Adjuvant;Automobile Driving;Autopsy;Behavior;Binding;Biopsy;causal variant;Cells;Characteristics;Chemicals;chemotherapy;Chromatin;cis acting element;Clinical;Clinical Trials;clinically relevant;Complex;CRISPR screen;cytotoxic;Cytotoxic agent;Data;Data Analyses;Development;drug action;Drug Combinations;drug repurposing;Drug resistance;Drug Screening;Elements;Event;Evolution;Excision;FDA approved;Female;Flow Cytometry;Formulation;fractionated radiation;Gene Expression;Gene Expression Regulation;gene network;Genes;Genetic;genetic predictors;Genetic Transcription;Glioblastoma;Glioma;Heterogeneity;high throughput screening;Hospitals;individual patient;insight;Intervention;Label;Letters;Link;Literature;Location;male;Malignant neoplasm of brain;Malignant Neoplasms;Maps;Mesenchymal;Methodology;MicroRNAs;model development;Modeling;Molecular;molecular subtypes;Multiomic Data;multiple omics;Mus;Mutation;neoplastic cell;non-genetic;novel;off-label use;Oncogenic;Oranges;Outcome;Pathway Analysis;Pathway interactions;patient response;Patient Selection;patient subsets;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Population;Population Heterogeneity;Predisposition;prevent;Process;Prognosis;promoter;Radiation therapy;Recurrence;Recurrent tumor;Regimen;Regulation;Research;Resistance;Resolution;response;Science;Selection for Treatments;Sensitivity and Specificity;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;Somatic Mutation;standard of care;stem-like cell;stressor;Survival Rate;System;Systems Biology;temozolomide;Testing;transcription factor;transcription regulatory network;transcriptome sequencing;tumor;tumor heterogeneity;tumor microenvironment;Tumor Subtype;Validation;Xenograft procedure

PROJECT_TITLE: Systems biology of intratumoral heterogeneity in glioblastoma

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


ED_INST_TYPE: SCHOOLS OF MEDICINE

ORG_CITY: CHAPEL HILL

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative Adoptive T cell therapy to treat human malignancies has been revolutionized by the use of chimeric antigen receptor (CAR) T cells in the past decade. However, despite the recent FDA approval of CAR T cells for the treatment of leukemia and lymphoma, how these CAR molecules really function remains largely unknown. Therefore, understanding how these novel molecules shape the function of T cells remains critical to logically advancing the field by designing molecules that reflect their true mode of action. In turn, these discoveries will be instrumental to generate more effective and safer therapies for patients with cancer.

PI_NAMEs: DOTTI, GIANPIETRO  (contact)

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Affect;Antibodies;antigen binding;Antigens;Attenuated;Automobile Driving;B lymphoid malignancy;cancer cell;CD19 gene;CD28 gene;Cell Physiology;Cell Respiration;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;Clinical Research;Clinical Trials;Complex;cytokine;Cytoplasm;Cytotoxic T-Lymphocytes;Data;design;Development;Engineering;Equilibrium;Event;exhaustion;gene therapy;Genes;Genetic Transcription;Human;Hyperactivity;Impairment;imprint;Kinetics;Lead;leukemia/lymphoma;Malignant Neoplasms;Mediating;Metabolic Pathway;Metabolism;metabolomics;Monoclonal Antibodies;neoplastic cell;novel;NR0B2 gene;overexpression;Patients;pharmacologic;Phosphatidylinositols;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;PIK3CG gene;Pre-Clinical Model;Predisposition;premature;Prevention;Proliferating;Protein Tyrosine Phosphatase;Proteins;Proteomics;Publishing;receptor;recruit;Reporting;response;Safety;Shapes;Side;Signal Pathway;Signal Transduction;Signaling Molecule;Solid Neoplasm;Speed;Synapses;T cell therapy;T Chain;T-Cell Activation;T-Cell Receptor;T-Cell Receptor Therapy;T-Lymphocyte;TNF gene;TNF Receptor-Associated Factors;transcriptome;tumor;Ubiquitin;Xenograft Model;Zinc Fingers

PROJECT_TITLE: Tuning CAR-T cell function

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


ADMINISTERING_IC: AR

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: PHILADELPHIA

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: PROJECT NARRATIVE  This study aims to elucidate the roles of decorin, a cartilage matrix molecule, in regulating the structure and mechanical properties of healthy and degenerative cartilage. We will determine how decorin contributes to the mechanical function of normal cartilage and the degradation of cartilage in osteoarthritis. We expect to reveal a new molecular mechanism that governs cartilage matrix assembly, which can be used for developing new strategies for cartilage regeneration and osteoarthritis treatment.

PI_NAMEs: HAN, LIN  (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: absorption;Acceleration;Adhesions;aggrecan;Atomic Force Microscopy;Biological;Biological Availability;Biomechanics;Biomimetics;Cartilage;cartilage degradation;Cartilage Matrix;cartilage regeneration;Catabolism;Cells;Chondrocytes;Collagen;Data;decorin;Degenerative polyarthritis;design;Development;Disease;Event;Experimental Designs;Extracellular Matrix;femur head;Future;Growth;Growth Factor;Health;Homeostasis;Impairment;improved;In Vitro;in vivo;Inflammatory;Injury;innovation;Insulin-Like Growth Factor I;Interleukin-1 beta;Joints;Knockout Mice;Leucine;Link;mechanical properties;Mechanics;Medial meniscus structure;Mediating;Modeling;Molecular;Mus;nanomechanics;normal aging;novel;old mice;Operative Surgical Procedures;Pathway interactions;Physiological;Play;postnatal;Production;Property;Proteoglycan;receptor;receptor binding;response;Role;Signal Transduction;Spectrum Analysis;Structure;Testing;Time;Transforming Growth Factor beta;Traumatic Arthropathy;Weight-Bearing state

PROJECT_TITLE: Biomechanics of Cartilage: Roles of Decorin in ECM Assembly and Degradation


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Depression;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Prevention;Rehabilitation;Women's Health Research

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative Psychological distress, presented through symptoms of depression and anxiety, is very common among breast cancer survivors, and it is critical that easily accessible, helpful, and engaging interventions are made available. IntelliCare, an app-delivered intervention, has been shown to be highly effective in reducing symptoms of depression and anxiety in the general population, suggesting strong potential for public impact among breast cancer survivors. This proposal will evaluate the efficacy of IntelliCare to reduce symptoms of depression and anxiety for breast cancer survivors, as well as the added value of human coaching to increase engagement, resulting in an adaptive intervention design for breast cancer survivors that is low cost, easily accessible, and highly efficient.

PI_NAMEs: CHOW, PHILIP  (contact)

PROGRAM_OFFICER_NAME: GRIMES, GENEVIEVE M

PROJECT_TERMS: adaptive intervention;Address;anxiety symptoms;arm;Attention;Breast Cancer survivor;cancer diagnosis;Cancer Survivor;cancer survivorship care;Caring;Classification;Clinical;clinically significant;Cognitive Therapy;cost;Data;depressive symptoms;design;Diagnosis;digital health;digital intervention;Distress;efficacious intervention;efficacy evaluation;efficacy testing;Enrollment;Equilibrium;experience;Experimental Designs;experimental study;Feedback;follow-up;Future;General Population;Goals;Health;Human;improved;improved outcome;Individual;innovation;Intervention;Interview;Longterm Follow-up;Malignant Breast Neoplasm;Malignant Neoplasms;member;Mental Health;Methods;mhealth interventions;mobile application;mood symptom;Outcome;Participant;Patient Education;patient engagement;Pattern;Perception;Personal Satisfaction;personalized approach;Pilot Projects;Population;post intervention;Precision Medicine Initiative;prevent;psychological distress;psychosocial;Psychosocial Assessment and Care;Public Health;Publishing;Randomized;reduce symptoms;Reporting;Research;Research Design;Sequential Multiple Assignment Randomized Trial;skills;smartphone application;social stigma;Step Tests;Structure;Survivors;survivorship;symptom treatment;Testing;therapy design;Time;Training;Woman

PROJECT_TITLE: Evaluating a mobile application to reduce distress in breast cancer survivors using an adaptive design

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics;Human Genome;Machine Learning and Artificial Intelligence

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: PROJECT NARRATIVE Transcription factor proteins bind to the human genome and regulate the genes that govern human health. Understanding how transcription factors find their regulatory targets on the genome informs us of how the diversity of cell types in the human body arises during development and how cells go wrong during disease. This project aims to develop machine learning tools for understanding how transcription factors find their DNA binding sites when they are expressed in cells.

PI_NAMEs: MAHONY, SHAUN AENGUS (contact)

PROGRAM_OFFICER_NAME: KRASNEWICH, DONNA M

PROJECT_TERMS: 3-Dimensional;Affinity;algorithm development;Behavior;Binding;Binding Proteins;Binding Sites;Cell Differentiation process;cell type;Cells;Chromatin;cohort;Collaborations;computerized tools;Development;Disease;DNA Binding;DNA-Binding Proteins;Environment;Event;Genes;Genome;genome-wide;Genomics;Goals;Health;Hematopoiesis;Human;Human body;Human Genome;Machine Learning;machine learning method;Methodology;Modeling;neural network architecture;Neurons;novel;Pattern;preference;programs;Research;Shapes;Site;Specific qualifier value;Specificity;synergism;System;tool;transcription factor;vertebrate genome

PROJECT_TITLE: Understanding the predeterminants of transcription factor regulatory activity

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences

ORG_CITY: ALBUQUERQUE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: While synapses within a single cell have long been known to be independently modified to allow the encoding of new information, the elements that allow these processes are thought to be relatively uniform across synapses. Thus, a fundamental gap exists in our knowledge as to whether unique protein signatures at individual synapses create functional differences in activity. This study seeks to determine whether proteins encoded by members of the neuron-specific gene family confer distinct functional properties to a subset of excitatory synapses, which could alter how neural networks respond to the flow of information during experience-dependent plasticity.

PI_NAMEs: WEICK, JASON P (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TERMS: Active Biological Transport;Acute;Address;Affect;Affective;AMPA Receptors;Animals;anxiety-like behavior;Behavior;behavior test;Behavioral;Brain;Cell surface;Cells;Chronic;cognitive function;Cultured Cells;Data;Dendritic Spines;Development;Disparate;Elements;ex vivo imaging;Excitatory Synapse;experience;Family;Family member;fear memory;Gene Family;Genes;Glutamates;Goals;Hippocampus;Image;In Vitro;Individual;information processing;Integral Membrane Protein;Knock-out;knockout animal;Knockout Mice;Knowledge;Label;Long-Term Potentiation;Maintenance;member;Mental Depression;Molecular;Molecular Profiling;Morphology;Motor;nerve supply;neural network;Neurons;novel;outcome disparities;overexpression;Pathway interactions;Pattern;Physiological;Play;Population;Post-Translational Protein Processing;postsynaptic;postsynaptic neurons;Preparation;Presynaptic Terminals;Process;Property;protein expression;protein transport;Proteins;Proteome;Publishing;receptor expression;recruit;Regulation;response;Role;Scaffolding Protein;Second Messenger Systems;Shapes;Signaling Protein;Site;Slice;Stimulus;subcellular targeting;Surface;Synapses;synaptic function;Synaptic plasticity;Techniques;Time;trafficking;Vesicle;Work

PROJECT_TITLE: Molecular mechanisms of excitatory postsynaptic diversity


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Nutrition;Obesity;Prevention;Rural Health;Social Determinants of Health

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: Project Narrative: In the US, sugar-sweetened beverages (SSB) is the largest contributor to added sugar intake, with SSB consumption in Appalachia twice as high as national estimates. Excessive SSB is also associated with numerous chronic health conditions (e.g., obesity, some cancers, type II diabetes, heart disease, dental caries). This efficacy trial evaluates a technology-based behavioral and health literacy intervention targeting SSB reduction and weight reduction/maintenance among rural Appalachia adults. The long-term goal of this research is to sustain an effective, scalable, and high reach intervention to improve SSB behaviors and reduce SSB-related inequities and chronic conditions in Appalachia and beyond.

PI_NAMEs: RITTERBAND, LEE M;ZOELLNER, JAMIE  (contact)

PROGRAM_OFFICER_NAME: JOHNSON, JARRETT AINSWORTH

PROJECT_TERMS: Address;Adherence;Adoption;Adult;Appalachian Region;Behavior;behavior change;Behavior Therapy;Behavioral;Beverages;Biological Markers;Body Weight decreased;Calories;Caring;Chronic;Community Services;Consumption;Coronary heart disease;cost;Data;Dental caries;design;Development;Diabetes Mellitus;diaries;Diet;dietary;digital divide;Effectiveness;efficacy evaluation;efficacy outcomes;efficacy trial;Energy Intake;evidence base;Evidence based intervention;follow-up;Food;Fruit;Future;Geography;Goals;Health;health inequalities;health literacy;Heart Diseases;Home;Hypertension;improved;Inequity;Intake;internet delivery;Intervention;Intervention Studies;Literature;Maintenance;Malignant Neoplasms;Mediation;Mediator;Medical;medically underserved;mHealth;Neighborhood Health Center;Non-Insulin-Dependent Diabetes Mellitus;nutrition;Obesity;Obesity associated cancer;Outcome;Participant;Patient Education;Pattern;Persons;Phase;post intervention;Prevention program;primary outcome;Process;programs;Provider;Public Health;Quality of life;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;Research;Resources;response;Risk Factors;Rural;Rural Appalachia;rural area;screening;secondary outcome;Services;soft drink;Source;Sports;Structure;sugar;sweetened beverage;System;Tea;Technology;technology intervention;Text Messaging;theories;Transportation;United States;Virginia;Voice;web site;web-based intervention;Weight

PROJECT_TITLE: iSIPsmarter: An RCT to evaluate the efficacy, reach, and engagement of a technology-based behavioral and health literacy intervention to reduce sugary beverages among rural Appalachian adults

STUDY_SECTION: CLHP

STUDY_SECTION_NAME: Community-Level Health Promotion Study Section[CLHP]


ADMINISTERING_IC: HL

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Dissemination and Implementation Research;Emergency Care;Health Services;Lung;Prevention

ORG_CITY: SAINT LOUIS

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE This study has the potential to positively impact public health by improving the implementation (deimplementation) and sustainment of evidence-based practices in the hospital setting. To do so, I propose adapting and testing an innovative, behavioral theory-driven deimplementation program called DRAUP in two intensive care units for proof of concept and support that the program can help providers and hospital organizations address context determinants of deimplementation. Study data will be used to optimize the intervention for a subsequent R01 trial, resulting in an independent research pathway, to improve the precision of care for critically ill patients.

PI_NAMEs: ABLORDEPPEY, ENYO  (contact)

PROGRAM_OFFICER_NAME: MASTERSON, MARY YAA SEDEGAH

PROJECT_TERMS: absorption;Accident and Emergency department;acute care;Address;Adoption;Area;Behavior;behavior change;Behavioral;behavioral construct;Behavioral Mechanisms;career;Caring;Case Study;Catheters;Chest;Clinical;Clinical effectiveness;Clinical Research;cost effectiveness;Cost Effectiveness Analysis;Critical Care;Critical Illness;Data;Deimplementation;design;Disease;dissemination science;Dose;effectiveness evaluation;effectiveness measure;effectiveness outcome;Electronic Health Record;Elements;Ensure;Environment;Equipment;evidence base;Evidence based practice;Exclusion;experience;Focus Groups;Frequencies;Future;Gatekeeping;Goals;Health;Healthcare;Healthcare Systems;hospital organization;Hospitals;Image;implementation evaluation;implementation outcomes;implementation research;implementation science;improved;Incentives;Individual;innovation;insight;Intensive Care Units;Intervention;intervention mapping;intervention program;Interview;K-Series Research Career Programs;Life;Literature;Measures;Medical;Medicine;Mentored Research Scientist Development Award;Mentorship;Methodology;Methods;Modeling;Motivation;National Heart, Lung, and Blood Institute;Operative Surgical Procedures;Pathway interactions;Patient Care;Patients;Perception;personalized care;Pilot Projects;Pneumothorax;point of care;Policies;Positioning Attribute;Process;Program Effectiveness;programs;Protocols documentation;Provider;Public Health;Qualitative Research;radiologist;Research;research study;Resources;Sample Size;Science;Services;Strategic vision;Structure;success;successful intervention;Surveys;Testing;theories;Thoracic Radiography;Training;trial design;ultrasound;United States;Universities;Venous;Washington;Work

PROJECT_TITLE: Adapting and testing a deimplementation program in the Intensive Care Unit


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Nanotechnology;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Radiation Oncology;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: This work proposes a new therapeutic strategy to deliver conventional or molecularly targeted therapies across the blood-brain barrier specifically to primary brain tumors. Studies will focus on medulloblastoma, the most common pediatric brain tumor in children, with the goals that brain tumor-specific drug targeting will enhance efficacy and minimize systemic side effects. Should our results prove favorable, we envision applicability to other primary brain tumors commonly seen in children and in adults as well as potential utility in neurological diseases with evidence of neuroinflammation including multiple sclerosis and stroke.

PI_NAMEs: HELLER, DANIEL ALAN (contact);RAJU, PRAVEEN B.

PROGRAM_OFFICER_NAME: FOUNTAIN, JANE W

PROJECT_TERMS: Address;Adult;Affinity;aggressive therapy;Antineoplastic Agents;Biochemical;Biodistribution;Biological Availability;Blood - brain barrier anatomy;bone;Brain;Brain Neoplasms;brain tissue;cancer cell;Cancer Etiology;Central Nervous System;Cephalic;Cerebellar Neoplasms;Cessation of life;chemotherapy;Child;Childhood Brain Neoplasm;childhood cancer mortality;Childhood Malignant Brain Tumor;Clinical;clinical application;Common Neoplasm;Compensation;conventional therapy;Dependence;Diagnosis;Disease;Distant;Dose;Drug Delivery Systems;Drug Kinetics;Drug Modulation;Drug Targeting;Drug toxicity;effective therapy;efficacy evaluation;Endothelial Cells;Endothelium;Excision;Extravasation;Gene Modified;Genetic;Genomics;Goals;imaging modality;Immunofluorescence Immunologic;improved;improved outcome;in vivo;Inflammation;inhibitor;Investigation;Ionizing radiation;irradiation;Knowledge;knowledge translation;Leptomeninges;Measurement;Mediating;Medulloblastoma;Metastatic Neoplasm to the Leptomeninges;microCT;Modeling;Molecular;Molecular Biology;molecular targeted therapies;Morbidity - disease rate;mouse model;multiphoton microscopy;Multiple Sclerosis;Mus;nanoparticle;nanoparticle delivery;nanoparticle drug;Neoplasm Metastasis;neoplastic cell;Nervous System Disorder;Neurocognitive Deficit;neuroinflammation;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;Outcome;P-Selectin;Pathway interactions;Patients;Pediatric Neoplasm;Pharmaceutical Preparations;Pharmacodynamics;Physiological;Pre-Clinical Model;precision drugs;precision medicine;Precision therapeutics;Primary Brain Neoplasms;primary endpoint;Primary Neoplasm;Radiation;Radiation Dose Unit;Radiation therapy;Research Personnel;Resistance;Role;Route;SHH gene;side effect;Sonic Hedgehog Pathway;standard of care;Stroke;synergism;systemic toxicity;targeted treatment;Technology;Therapeutic;Therapeutic Agents;Therapeutic Index;therapy resistant;Toxic effect;Treatment Efficacy;treatment strategy;Treatment-related toxicity;tumor;Tumor Tissue;uptake;Vertebral column;Vincristine;Work

PROJECT_TITLE: Tumor-Selective Delivery Approaches for Medulloblastoma

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: PROJECT NARRATIVE Many mucosal epithelial cells project elaborate protrusions on their apical surfaces, called microridges, which help adsorb and retain mucus. The Sagasti lab has established a zebrafish model to investigate the morphogenesis of these understudied protrusions, revealing novel mechanisms by which the actomyosin cortex, cytolinkers, and intermediate filaments contribute to protrusion morphogenesis. Future work will investigate how cortical contractility is temporally and spatially regulated to promote microridge morphogenesis, and identify additional regulatory proteins that build the microridge cytoskeletal scaffold.

PI_NAMEs: SAGASTI, ALVARO  (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Achievement;Actins;Actomyosin;Adsorption;Apical;Biomechanics;Cell Physiology;Cell surface;Cells;Cellular biology;Cornea;Cytokeratin filaments;Cytoskeleton;Data;Dissection;Dryness;Endowment;Epithelial Cells;Epithelium;experimental study;Future;genetic regulatory protein;Image;Infection;Intercellular Junctions;Intermediate Filaments;Length;Modeling;Molecular;Morphogenesis;Morphology;Mucous body substance;Mucous Membrane;Myosin ATPase;novel;Oral cavity;Pattern;Periodicals;Process;protein crosslink;Proteins;Research;Role;scaffold;Skin;Structure;Study models;Surface;Surface Tension;Tissues;Work;Zebrafish

PROJECT_TITLE: Mechanisms of microridge protrusion morphogenesis on mucosal epithelial cells

STUDY_SECTION: MRAC

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


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Cancer;Dental, Oral, and Craniofacial Disease;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative African-Americans have a five-fold incidence of ameloblastoma than Caucasians. One quarter of all post-surgical ameloblastoma recurrence occur in the Black racial group. Full understanding of mechanisms promoting ameloblastoma recurrence are needed to mitigate disparities in ameloblastoma treatment outcomes.

PI_NAMEs: AKINTOYE, SUNDAY O (contact)

PROGRAM_OFFICER_NAME: WOODHOUSE, ELIZABETH

PROJECT_TERMS: African American population;Ameloblastoma;angiogenesis;Autophagocytosis;Autophagosome;Bioenergetics;Biological;Biological Markers;Black Populations;Black race;BRAF gene;cancer stem cell;Caucasians;CD34 gene;Cell Line;Cell Survival;Cells;Characteristics;Clinical;cohort;Colorectal Cancer;comparative;Complex;Cysteine-Rich Domain;Cytoprotection;Death Rate;density;Disparity;disparity reduction;DNA Sequence Alteration;Drosophila pros protein;ENG gene;Epithelium;Growth;GTF2H1 gene;Head and Neck Neoplasms;Hypoxia;Hypoxia Inducible Factor;in vivo;Incidence;Knowledge;MAP Kinase Gene;Mediating;Mesenchymal;migration;Modeling;Mus;Mutation;Neoplasm Metastasis;neoplastic;neoplastic cell;Nutrient;Odontogenic Tumors;Oncogenes;Oncogenic;Operative Surgical Procedures;Oxidative Stress;Pathway interactions;Patients;Pattern;PECAM1 gene;Phagocytosis;Phenotype;Phosphotransferases;Prevalence;prognostic indicator;Prognostic Marker;prognostic value;Property;Protein-Serine-Threonine Kinases;Proteins;Proto-Oncogene Proteins B-raf;Race;racial disparity;racial diversity;racial health disparity;racial population;Recurrence;Recycling;Residual state;Running;Sampling;Signal Pathway;stemness;Stress;survival outcome;Testing;therapy resistant;Tissues;trafficking;Treatment outcome;tumor;tumor microenvironment;Tumor Promotion;Variant

PROJECT_TITLE: Biological Indicators of Racial Disparity in Ameloblastoma Recurrence

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-Y(55)R]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Microbiome

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative The microbes present in our gut have a profound impact on health, and profoundly influence the human immune system. In this proposal, we characterize specific immunologically-active lipids produced by the microbes in our intestines. We further investigate how these lipids shape immunity by regulating natural killer T cells, a specialized group of immune cells that recognizes lipids.

PI_NAMEs: BRENNAN, PATRICK JOSEPH (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Address;Affect;Allergic Disease;alpha-galactosylceramide;Anaerobic Bacteria;Animal Model;anomer;Antigens;Archaea;Bacteria;Bacteroides fragilis;Binding;Biochemical;Cell Count;Cells;Chronic;Collaborations;Colon Carcinoma;Complex;Cytotoxic T-Lymphocytes;Data;Diet;Digestive System Disorders;Disease;Dose;effector T cell;Enteral;enteric infection;Environment;experimental study;Exposure to;feeding;Food Hypersensitivity;Fractionation;Future;Gastrointestinal Diseases;Genomic approach;Germ-Free;gut microbes;gut microbiota;Health;Histocompatibility;Homeostasis;Host Defense;Human;Immune;Immune response;Immune system;Immunity;Immunologics;immunoregulation;Infant;Inflammatory Bowel Diseases;Intestines;Knowledge;Life;Link;Lipids;Lymphocyte;Lymphocyte Subset;Malignant Neoplasms;Mass Spectrum Analysis;member;mesenteric lymph node;Metabolic Diseases;Methanobrevibacter;Methods;Microbe;microbial;microbial products;microbiota;microorganism;Modeling;Molecular;mouse model;Mucous Membrane;Mus;mutant;Nature;novel;Outcome Study;Pathway interactions;Phenotype;Play;Population;Property;receptor;Recombinants;Reporting;Role;Series;Shapes;single-cell RNA sequencing;Source;stereochemistry;Structure;sugar;symbiont;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;Testing;Therapeutic;transcriptomics

PROJECT_TITLE: Lipid Antigens for iNKT Cells in the Gut Microenvironment

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


NIH_SPENDING_CATS: Cardiovascular;Congenital Structural Anomalies;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: LEXINGTON

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Project Narrative Marfan syndrome is a genetic condition that causes thoracic aortic aneurysm, a life-threatening dilation of the largest blood vessel in the body. This research project will examine how statin medicines prevent thoracic aortic aneurysm growth and whether they add benefit to the medicines currently used to treat thoracic aortic aneurysm in Marfan syndrome.

PI_NAMEs: SHEPPARD, MARY BURCHETT (contact)

PROGRAM_OFFICER_NAME: HUANG, LI-SHIN

PROJECT_TERMS: 3-hydroxy-3-methylglutaryl-coenzyme A;Adrenergic Receptor;Aneurysm;Angiotensin Receptor;Animal Model;antagonist;Aorta;Aortic Aneurysm;Aortic Diseases;Aortic Rupture;Area;ascending aorta;Atenolol;Attenuated;Basic Science;Biological Assay;Blood Vessels;career;Cause of Death;Cell Fractionation;Cell membrane;Cellular Membrane;Cholesterol;Cholesterol Homeostasis;Clinic;Clinical Research;clinically relevant;college;Confocal Microscopy;Cultured Cells;Data;Diagnosis;Disease;Dissection;Elasticity;Elastin;Etiology;experimental study;Faculty;farnesyl pyrophosphate;Farnesyl Transferase Inhibitor;farnesylation;FBN1;Fluorescence-Activated Cell Sorting;Funding;Future;Gel;Gelatinase A;Genetic Diseases;Genetic Predisposition to Disease;Goals;Growth;Human;Hypertension;Immunohistochemistry;in vivo;Incubated;Infusion procedures;insight;interest;Kentucky;Laboratories;Laboratory Study;Lead;Learning;Leukocytes;Life;Losartan;Marfan Syndrome;Matrix Metalloproteinases;Measurement;Measures;Medical Genetics;Medicine;Mentors;Microscopy;mouse model;Mus;new therapeutic target;novel therapeutics;Operative Surgical Procedures;Oxidoreductase;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacology;Physicians;Plasma;Pravastatin;pre-clinical research;prevent;Production;professor;Proteins;Publications;RAS inhibition;Regimen;Renin-Angiotensin System;repaired;Research;Research Personnel;Research Project Grants;Retrospective Studies;Risk;Scientist;Senior Scientist;sexual dimorphism;Signal Transduction;Signaling Molecule;skills;Smooth Muscle Myocytes;standard of care;Techniques;Testing;Therapeutic Uses;Thoracic aorta;Thoracic Aortic Aneurysm;Tissues;Training;Transforming Growth Factor beta;translational study;ultra high resolution;ultrasound;United States National Institutes of Health;Universities;Vascular Diseases;Vascular Smooth Muscle;Work

PROJECT_TITLE: Pharmacological Mechanistic Insights into Thoracic Aortic Aneurysm


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: GAINESVILLE

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: NARRATIVE Infectious disease is a pervasive problem in human heath. The continuing goal of this training program in Basic Microbiology and Infectious Disease is to provide exceptional training in the mechanisms of infectious disease that bridges the gap between basic and clinical science. This will help enhance the quality of the biomedical research workforce in the United States.

PI_NAMEs: KARST, STEPHANIE M (contact)

PROGRAM_OFFICER_NAME: SASTALLA, INKA I

PROJECT_TERMS: Communicable Diseases;Microbiology

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Advisory Committee[MID]


NIH_SPENDING_CATS: Cancer;Genetics;Immunotherapy;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: PHYSIOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: NARRATIVE The aberrant presence of double-stranded nucleic acids in the cytoplasm promotes a robust inflammatory re- sponse, which has galvanized interest in developing therapies that can sensitize cancer cells to the immune system. However, we found that cancer cells with chronic inflammation - fueled by genomic instability – have adapted resistance to a key innate immune pathway called cGAS-STING, redirecting a normally lethal output towards alternative pathways that promote metastasis. Motivated by the discovery that these resistant cells can still be sensitized to immune attack in a manner independent of cGAS-STING, we aim to unravel the con- text-dependence of this versatile signaling cascade to test if restoring normal responses to inflammation can be used as an effective therapeutic strategy to sensitize tumors to immune therapy.

PI_NAMEs: LAUGHNEY, ASHLEY MARIE (contact)

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: Agonist;anti-tumor immune response;Antitumor Response;autoinflammatory;Back;Biological Assay;Breast Cancer Model;Bypass;cancer cell;cancer cell differentiation;Cell Differentiation process;Cell Shape;Cells;Chromosomal Instability;Chronic;Clustered Regularly Interspaced Short Palindromic Repeats;combinatorial;CXCL10 gene;Cyclic GMP;cytokine;Cytoplasm;Cytosol;Data;Dependence;Development;DNA;Double-Stranded RNA;ds-DNA;early phase clinical trial;Embryonic Development;epithelial stem cell;experimental study;Gene Activation;Gene Silencing;Gene Targeting;genetic manipulation;Genetic Transcription;Genetically Engineered Mouse;Genomic Instability;Human;Immune;immune activation;immune checkpoint blockade;immune resistance;Immune response;Immune system;Immunotherapy;In Vitro;in vivo;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;innate immune pathways;interest;Interferon Type I;Interferons;Invaded;Knock-out;Link;Logic;Malignant neoplasm of lung;Malignant Neoplasms;Mammalian Cell;Maps;Mediating;Mediator;Medicine;mouse model;Mus;Mutagenesis;Nature;Neoplasm Metastasis;neoplastic cell;Normal Cell;novel;Nucleic Acids;Output;pancreatic cancer model;Pathway interactions;Phenotype;Predisposition;Process;Production;programs;Reporter;Resistance;resistance mechanism;response;Role;sensor;Signal Transduction;single cell sequencing;Source;stem;stem cells;Stimulator of Interferon Genes;Stimulus;STING1 gene;synergism;System;Testing;Therapeutic;therapeutically effective;therapy development;Thinking;tissue regeneration;transcription factor;Transplantation;tumor;tumor heterogeneity;Tumor Immunity;Tumor Promotion;type I interferon receptor;vector;Viral;Work;wound healing

PROJECT_TITLE: Probing cytosolic nucleic acid sensing pathways in cancer


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biotechnology;Hematology;Immunotherapy;Infectious Diseases;Lung;Pediatric;Pneumonia;Pneumonia and Influenza;Prevention;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: CHARLESTON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Statement of Relevance Transplant-related complications including idiopathic pneumonia syndrome (IPS) are major contributors to the development of multiple organ dysfunction syndrome after allogeneic hematopoietic stem cell transplantation (HSCT) and continue to limit successful outcomes following this otherwise lifesaving procedure particularly in the pediatric population. The development of novel strategies to reduce the incidence and severity of these complications or treat the life-threatening aspects of each once established remains one of the most significant challenges facing our pediatric HSCT patients. Experiments proposed in this application will enhance our understanding of how alarmins and their receptors contribute to lung injury with the potential to modulate these pathways to reduce the severity of respiratory failure in pediatric HSCT recipients, and thereby improved outcomes and extend the use of HSCT as well as other novel cellular therapies.

PI_NAMEs: PACZESNY, SOPHIE  (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Acute Lung Injury;Allogenic;Alveolar;Binding;Biological;Biological Markers;Blood;Bone Marrow Transplantation;Cell Therapy;cell type;Cells;Childhood;Chimera organism;Clinical;Clinical Data;clinical investigation;Clinical Trials;Correlative Study;curative treatments;Cytoprotection;Data;Detection;Development;Disease;Educational workshop;Effector Cell;effector T cell;Endothelium;Epithelial Cells;Epithelium;Equilibrium;Eragrostis;experimental study;Frequencies;Functional disorder;Genetic;graft vs host disease;Hematology;Hematopoietic;Hematopoietic Stem Cell Transplantation;Idiopathic pneumonia syndrome;IL9 gene;improved;improved outcome;Incidence;Inflammation;insight;Interferon Type II;Interleukin-9;Interleukins;Journals;Knowledge;Laboratories;Life;Lung;lung injury;Lymphoid Cell;Malignant - descriptor;Mediating;Membrane;Minor;Modeling;Molecular;Monoclonal Antibodies;mortality;Multiple Organ Failure;neutralizing antibody;neutralizing monoclonal antibodies;new therapeutic target;Non-Malignant;novel;novel strategies;Outcome;Pathogenesis;Pathogenicity;Pathway interactions;Patients;pediatric patients;Plasma;Population;pre-clinical;Pre-Clinical Model;prevent;Procedures;Production;prophylactic;protective effect;Proteome;PTPRC gene;radioresistant;receptor;Regimen;Regulation;Regulatory T-Lymphocyte;Residual state;Respiratory Failure;response;Risk;Risk Reduction;risk stratification;Role;Severities;Severity of illness;Signal Transduction;small molecule;Source;Stromal Cells;success;T-Lymphocyte;Testing;Therapeutic;Translating;translational medicine;Translational Research;Transplant Recipients;Transplantation;United States National Institutes of Health

PROJECT_TITLE: IL-33 induced-lL-9 producing type 2 innate lymphoid cells in the regulation of acute lung injury after hematopoietic stem cell transplantation (HSCT) in pediatric patients

STUDY_SECTION: TTT

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


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Public health relevance This proposal incorporates leading-edge genetic and physiological studies to investigate contractile proteins that govern cardiac muscle performance in health and in disease. Therefore, the health relevance of the proposal is substantial and highly significant to the mission of the National Institutes of Health.

PI_NAMEs: METZGER, JOSEPH MARK (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Actins;Affect;Binding;Biosensor;Cardiac;Cardiac Myocytes;Cardiac Myosins;Cells;clinical translation;Complex;Contractile Proteins;Country;Disease;experimental study;Fluorescence Resonance Energy Transfer;Foundations;Functional disorder;Genetic;Genetic Diseases;Genetic Models;Health;Heart;Heart Diseases;Heart failure;heart function;Human;Hypertrophic Cardiomyopathy;Inherited;innovation;insight;ischemic cardiomyopathy;Kinetics;Knockout Mice;Length;Ligands;Methodology;Microfilaments;Mission;Modification;Molecular;Molecular Conformation;Morbidity - disease rate;mortality;Muscle Cells;Muscle Contraction;Mutation;Myocardial Ischemia;Myocardium;Myosin ATPase;myosin-binding protein C;novel therapeutics;Pathogenesis;Performance;Permeability;Persons;Physiological;Play;Proteins;public health relevance;Pump;Regulation;Role;Sarcomeres;Signal Transduction;small molecule;System;Tertiary Protein Structure;Testing;Therapeutic;Thick;Thick Filament;Thin Filament;Thinness;Time;Tropomyosin;Troponin;Troponin I;United States National Institutes of Health

PROJECT_TITLE: Myofilaments as regulators of heart function in disease

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Brain Disorders;Genetics;HIV/AIDS;Infectious Diseases;Mental Health;Neurodegenerative;Neurosciences

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative HIV-associated neurocognitive disorder is a devastating disease that affects approximately 50% of people with HIV. While the exact cause of HAND is likely variable and multifactorial, evidence suggest that altered metabolism and reduced bioenergetic capacity in the brain may contribute to the disease. These proposed studies will probe underlying mechanisms of metabolic alterations and reduced bioenergetic capacity in the brain, which may lead to novel therapeutic interventions for HAND and other neurodegenerative diseases.

PI_NAMEs: FIELDS, JEREL ADAM (contact)

PROGRAM_OFFICER_NAME: RAO, VASUDEV RAMACHANDRA

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Acute;Address;Affect;Aging;Agonist;Anti-Inflammatory Agents;antiretroviral therapy;Area;Astrocytes;Autopsy;Basic Science;Behavioral Sciences;Bioenergetics;Biogenesis;Brain;brain cell;brain control;Brain Diseases;brain tissue;Buffers;cannabinoid receptor;Chronic;Cognitive;comorbidity;comparison control;cytokine;Data;Disease;Excess Mortality;Exhibits;Exposure to;Extracellular Space;Gene Expression;Genetic;Glucose;Glutamine;Glycolysis;HIV;HIV Envelope Protein gp120;HIV Infections;HIV-associated neurocognitive disorder;Homeostasis;Human;In Vitro;in vitro Model;Infection;Inflammatory;Interleukins;knock-down;Lactate Transporter;Learning;Link;Location;Memory;Metabolic;Metabolism;Microglia;Mitochondria;mitochondrial dysfunction;Mitochondrial Proteins;monocyte;mortality risk;mouse model;Mus;Neurodegenerative Disorders;neuroinflammation;Neurologic Dysfunctions;Neuronal Dysfunction;neuronal metabolism;Neurons;neuropathology;neurotoxic;neurotoxicity;neurotrophic factor;novel therapeutic intervention;Oxidative Phosphorylation;Persons;Pharmaceutical Preparations;Phase;Phenotype;Play;Prevalence;prevent;Process;Production;Proteins;Quality of life;release factor;Reporting;Research;Research Priority;Role;Seminal;Specimen;Stimulus;Tenofovir;Testing;Therapeutic;transcription factor;Transgenic Mice;Viral;Viral Load result;Viral Proteins;Virus;Work

PROJECT_TITLE: The role of TFAM alterations in HIV- and ART-induced mitochondrial dysfunction in the brain

STUDY_SECTION: HCCS

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


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

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: PROJECT NARRATIVE Patients with MLL1-rearranged acute leukemia exhibit particularly poorer clinical outcomes, demanding effective treatments. This proposal aims to characterize a previously unknown non-canonical oncogenic function of EZH2, which contributes to aggressive tumor phenotypes, and develop a novel therapeutic strategy and generate a promising drug candidate for treating MLL1-rearranged leukemias. Therefore, the proposed research is directly relevant to public health.

PI_NAMEs: JIN, JIAN ;WANG, G GREG  (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Accounting;Acute leukemia;Acute Lymphocytic Leukemia;Affect;antitumor effect;Binding;Biological Availability;c-myc Genes;cancer cell;Cancer Model;Cancer Patient;Catalytic Domain;CCNE1 gene;Cell model;Chemicals;Chromatin;Clinical;cofactor;Complex;design;Development;Disease;Dissection;Dose;drug candidate;Drug Kinetics;Drug Targeting;effective therapy;Enhancers;EP300 gene;Exhibits;EZH2 gene;Gene Activation;gene repression;Genes;Genetically Engineered Mouse;genomic profiling;Goals;Histone H3;histone methylation;histone methyltransferase;Histones;Homologous Gene;Human;improved;In Vitro;in vivo;Infant;inhibitor;innovation;insight;knock-down;Knock-out;Lead;lead series;Left;leukemia;Leukemic Cell;Ligands;Link;Lysine;Mediating;MLL gene;Modeling;Mus;neoplastic cell;novel;novel therapeutic intervention;novel therapeutics;Oncogene Activation;Oncogenes;Oncogenic;Oncoproteins;Oral;Outcome;Pathway interactions;patient derived xenograft model;Patients;pediatric acute leukemia;Phenotype;Polycomb;Prognosis;Property;Protac;Public Health;Publishing;recruit;Reporting;Repression;Research;response;Role;Series;Site;small molecule;Solid;standard care;targeted treatment;Technology;Testing;Therapeutic;therapeutic candidate;Therapeutic Effect;Transactivation;tumor;tumorigenesis;tumorigenic;ubiquitin-protein ligase;Xenograft procedure

PROJECT_TITLE: Dissecting and targeting canonical and non-canonical oncogenic functions of EZH2 in caner

STUDY_SECTION: DMP

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Hematology;Human Genome;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: NARRATIVE Myelodysplastic Syndromes (MDS) are blood cancers with increasing incidence with aging and in cancer survivors and limited therapeutic options. The field lacks adequate MDS models to facilitate hypothesis- and preclinical-testing. The proposed work utilizes a breakthrough humanized mouse recipient to build xenograft models, and then validate both the engrafting material and its response to standard therapy.

PI_NAMEs: GRIMES, H. LEIGHTON (contact);HALENE, STEPHANIE

PROJECT_TERMS: Acceleration;Affect;Aging;aging population;Allogenic;Antibodies;Azacitidine;Biological;Biopsy;Cancer Model;Cancer Survivor;Categories;Cell surface;cell type;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Clonality;comparative;conditioning;curative treatments;cytokine;Data;Data Set;Decitabine;Dendritic Cells;Development;Diagnosis;Diagnostic;Disadvantaged;Disease Progression;DNA Sequence Alteration;DNA sequencing;Dose;Dysmyelopoietic Syndromes;Engraftment;Epigenetic Process;epigenome;Erythroid;Frequencies;Future;Genetic;Genetic Transcription;Genetically Engineered Mouse;Genomics;Genotype;Hematologic Neoplasms;Hematopoietic;Hematopoietic Neoplasms;Hematopoietic stem cells;high risk;Histologic;Human;human data;humanized mouse;improved;Incidence;Individual;Interleukin-15;irradiation;Knock-in;leukemia;Libraries;Link;Macrophage;Macrophage Colony-Stimulating Factor;Marrow;Measures;Modeling;Modification;Molecular;monocyte;mouse model;multiple omics;Mus;mutant;Mutation;new therapeutic target;novel therapeutics;Osteoclasts;Patients;Pharmacodynamics;Phenotype;Physiological;Population;pre-clinical;Preclinical Testing;Production;programs;Proto-Oncogene Protein c-kit;Publishing;repaired;Reproducibility;Research;Resistance;response;Risk;Sampling;single cell analysis;single cell technology;standard of care;stem cell niche;Stem cell transplant;targeted treatment;Technology;Therapeutic;Therapeutic Agents;transcriptome;Transitional Cell;treatment response;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Modeling myelodysplasia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-N(55)R]


NIH_SPENDING_CATS: Cardiovascular;Rare Diseases

PHR: Project Narrative Group 2 innate lymphoid cells (ILC2) and eosinophils are both innate immune cells, but their participation in abdominal aortic aneurysms (AAA) has never been examined, although blood eosinophil counts are significantly higher in patients with AAA than in those without AAA. This study is proposed to test a role of ILC2 in the development of mouse AAA by releasing interleukin-5 to regulate the expansion and function of eosinophils.

PI_NAMEs: LIBBY, PETER  (contact)

PROGRAM_OFFICER_NAME: CHARETTE, MARC F

PROJECT_TERMS: Abdominal Aortic Aneurysm;abdominal wall;Acceleration;Adhesions;Adoptive Transfer;Affect;Allergic;angiogenesis;Angiotensin II;Antibodies;Aorta;Apolipoprotein E;Apoptosis;Atherosclerosis;Attenuated;Blood;blood pressure control;Bone Marrow;Bone Marrow Transplantation;Cardiovascular Diseases;cell type;Cells;Cessation of life;cytokine;Development;Diphtheria Toxin;Endothelium;eosinophil;Eosinophil cationic protein;Event;General Population;Growth;Human;Human Activities;IL4 gene;IL5 gene;Immune;Inflammation;Infusion procedures;Injury;Interferon Type II;Interleukin-10;Interleukin-13;Interleukin-5;Lesion;Life Style;Link;Lymphocyte;Lymphoid Cell;Macrophage;Mediating;Mediator;migration;Modeling;Molecular;monocyte;mortality;mouse development;Mus;neutrophil;Obesity;Operative Surgical Procedures;Parasitic infection;Patients;Peripheral;Pharmaceutical Preparations;Plasma;Play;Prevalence;Proteins;Recombinants;Reporting;response;Risk Factors;Role;Site;smoking cessation;Stents;subcutaneous;Testing;Wild Type Mouse

PROJECT_TITLE: Role of ILC2 and eosinophils in abdominal aortic aneurysm

STUDY_SECTION: AICS

STUDY_SECTION_NAME: Atherosclerosis and Inflammation of the Cardiovascular System Study Section[AICS]


ORG_CITY: PITTSBURGH

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Narrative: Despite significant improvement in short-term survival of organ transplants, attrition of transplanted organs over time remains a significant clinical problem. Exploring novel mechanisms by which the recipient’s immune system responds to the foreign organ would lead to better donor/recipient matching and novel therapies that enhance long-term graft and patient survival.

PI_NAMEs: LAKKIS, FADI G. (contact);METES, DIANA M

PROGRAM_OFFICER_NAME: KULKARNI, SHILPA S

PROJECT_TERMS: Acceleration;Acute;adaptive immune response;Adult;Adverse effects;Allogenic;Allografting;Antibodies;Antigen Presentation;Applications Grants;Arterial Disorder;B-Lymphocytes;Biopsy;Biopsy Specimen;Cells;Cessation of life;Chronic;Clinic;Clinical;clinical practice;cohort;Coupled;cytotoxic;Data;Dendritic Cells;donor-specific antibody;druggable target;Failure;Fibrosis;Gene Expression Profile;Genes;Genetic Transcription;Genotype;graft failure;graft function;Graft Survival;HLA Antigens;Human;human data;human leukocyte antigen testing;Immune system;Immunosuppression;improved;Inflammation;Injury;innovation;insight;interstitial;kidney allograft;Kidney Transplantation;Living Donors;Longevity;Macrophage;Mediating;Membrane;Memory;memory acquisition;Molecular;monocyte;Mus;novel;novel therapeutics;Organ;Organ Survival;Organ Transplantation;Outcome;Pathologic;Pathology;Pathway interactions;Patients;peripheral blood;Phenotype;post-transplant;premature;Protocols documentation;response;Risk;Risk Factors;Role;SHPS-1 protein;Signaling Molecule;sobriety;statistics;T-Lymphocyte;Testing;Time;Translating;Transplant Recipients;Transplantation

PROJECT_TITLE: Innate Allorecognition in Clinical Organ Transplantation


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Bioengineering;Data Science;Machine Learning and Artificial Intelligence;Prevention;Social Determinants of Health

ORG_CITY: NEWARK

ORG_NAME: RUTGERS THE STATE UNIV OF NJ NEWARK

ORG_STATE: NJ

PHR: Project Narrative Statement of Relevance to Public Health Being able to ensure privacy and security while enabling data sharing and analysis is critical to pave the way forward for public health research and improve our understanding of diseases. The proposed work will address the challenges that impede the use of data across all of the different modalities of data sharing. The integration into existing platforms will ensure that the developed models, tools, and solutions directly impact the research community and improve public health interventions.

PI_NAMEs: VAIDYA, JAIDEEP  (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: biomedical data science;Biomedical Research;care fragmentation;cohort;Collaborations;Communities;Complex;cost;Data;Data Analyses;Data Collection;Data Commons;data modalities;Data Science;data sharing;deep learning;Diabetes Mellitus;Disease;Economics;Ensure;Goals;Healthcare;improved;Institution;Lead;Learning;Malignant Neoplasms;Modeling;Modernization;Nature;new technology;novel;open source;Pathway interactions;patient privacy;Prevention;Privacy;programs;Public Health;public health intervention;public health research;Research;Risk;Security;social;Software Tools;Statutes and Laws;Substance abuse problem;success;Techniques;Technology;tool;usability;Work

PROJECT_TITLE: Developing novel technologies that ensure privacy and security in biomedical data science research

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


ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Project Narrative The proposed study will take multiple genetic and biochemical approaches to tackle two novel nutrient-related problems that are related to human health. The first is to uncover the unexpected beneficial roles of metabolites from the bacterial cell wall to animal development and behaviors, as well as understand the underlying mechanism. The second is to uncover a gut-initiated pathway that senses the imbalance of nucleotides to regulate germ cell proliferation and nucleotide metabolism.

PI_NAMEs: HAN, MIN  (contact)

PROGRAM_OFFICER_NAME: BLATCH, SYDELLA ANNE

PROJECT_TERMS: Amino Acids;Animals;Behavior;Behavioral;Biochemical;Biological Assay;Biology;Caenorhabditis elegans;Cell Proliferation;Cell Wall;Cellular Metabolic Process;commensal microbes;Data;deprivation;detection of nutrient;Development;Diet;endonuclease;Enterobactin;Event;fascinate;Fatty Acids;Genetic;Germ Cells;Glucose;Grant;Health;Human;Immune;innovation;Integration Host Factors;Intestines;Investigation;Mammalian Cell;Metabolic;microbiota;Micronutrients;Modeling;Mus;Nematoda;novel;nucleotide metabolism;Nucleotides;Nutrient;Nutritional;Organism;Pathway interactions;Peptidoglycan;Physiological;Physiology;Pyrimidine;Recording of previous events;reproductive fitness;Research;response;Role;Siderophores;Signal Transduction;Structure;System;Variant

PROJECT_TITLE: Novel Nutrient Functions and Sensing Mechanisms

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


NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

PHR: Narrative Epithelial cells employ components of the epithelial-mesenchymal transition (EMT) program as the main route for entering into the stem cell state with enhance tumor-initiating ability and a greater propensity to acquire resistance to chemotherapeutics. We have identified a TGFβ-regulated EMT program that induces the generation of tumor initiating cells through the reactivation of a silenced pluripotent lncRNA which induces tumor-mediated immunosuppression and tumor cell innervation. A comprehensive molecular characterization of the pathways mediating EMT is vital to our ability to therapeutically target tumor progression and metastasis.

PI_NAMEs: HOWE, PHILIP H (contact)

PROGRAM_OFFICER_NAME: HILDESHEIM, JEFFREY

PROJECT_TERMS: Adult;Automobile Driving;axon guidance;Breast Cancer Model;breast cancer progression;breast tumorigenesis;cancer cell;cancer stem cell;cell mediated immune response;Cell Physiology;Cell surface;Cells;Cellular Immunity;chemokine;Chemoresistance;Clinical;Code;conventional therapy;cytokine;Data;design;differential expression;effector T cell;Embryonic Induction;Epigenetic Process;Epithelial Cells;Epithelium;Epitopes;Exhibits;experimental study;Gene Expression Profile;Generations;Genetic Transcription;Goals;Heterogeneous-Nuclear Ribonucleoproteins;High-Throughput RNA Sequencing;Homologous Gene;Immune;Immunoglobulin Domain;Immunoglobulins;Immunosuppression;In Vitro;in vivo;Informatin;Injections;Ligands;Malignant Breast Neoplasm;Malignant Epithelial Cell;Malignant Neoplasms;mammary;mammary epithelium;Mammary gland;Mammary Neoplasms;Mammospheres;Mediating;member;Mesenchymal;Metastatic Neoplasm to the Lung;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;Neoplasm Metastasis;neoplastic cell;nerve supply;neurogenesis;neuron development;neuronal tumor;new therapeutic target;novel;Organ;Outcome;Pathway interactions;Phosphorylation;pluripotency;Primary Neoplasm;Production;programmed cell death ligand 1;programs;Property;receptor;Regulation;Relapse;Resistance;RNA-Binding Proteins;Role;Route;SET Domain;Signal Pathway;Signal Transduction;stem cells;stemness;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;Therapeutic;Therapeutic Intervention;therapeutic target;Tissues;Transcript;Transforming Growth Factor beta;tumor;tumor initiation;tumor progression;Tumor Promotion;Tumorigenicity;Untranslated RNA

PROJECT_TITLE: TGFbeta-regulated epithelial-mesenchymal transition (EMT)

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Genetics;Hematology;Neurosciences;Rare Diseases

ORG_CITY: Columbus

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: OHIO STATE UNIVERSITY

PHR: PROJECT NARRATIVE Genes encoding enzymes in the tricarboxylic acid cycle (TCA cycle, also known as the Krebs cycle) are causative genetic lesions in human cancers, including both inherited tissue-specific tumor syndromes and a variety of sporadic cancers. These tumors are associated with the accumulation of oncometabolites which interfere with an enzyme family of ~70 members that use alpha-keto-glutarate (aKG, also known as 2-oxo-glutarate) as a cofactor. In this application, we will use a CRISPRi-based screen to identify and perform pilot validation of the aKG-dependent enzyme(s) whose inhibition by oncometabolites leads to the acquisition of the neoplastic phenotype.

PI_NAMEs: KIRSCHNER, LAWRENCE S (contact)

PROGRAM_OFFICER_NAME: CERO, CHERYL

PROJECT_TERMS: Acute Myelocytic Leukemia;Aerobic;Affect;aldehyde dehydrogenases;alpha ketoglutarate;Biological Models;Cancer Etiology;Cell Line;Cell model;Cell Physiology;Cells;Cellular Metabolic Process;Characteristics;Citric Acid Cycle;Clear Cell;Clustered Regularly Interspaced Short Palindromic Repeats;cofactor;Collagen;Correlative Study;CRISPR interference;CRISPR/Cas technology;Data;Data Set;Disease;DNA;DNA Modification Process;Elderly;Endocrine;Enzyme Inhibition;Enzymes;Epithelium;Eukaryotic Cell;Familiarity;Family;Family member;Fumarate Hydratase;Future;Gastrointestinal Stromal Tumors;gene repression;Generations;Genes;Genetic;Glioblastoma;Glioma;Hereditary Paraganglioma;high risk;histone demethylase;Histones;Human;Hydroxylation;in silico;In Vitro;in vivo;in vivo Model;Inherited;Investigation;Isocitrate Dehydrogenase;knock-down;Knowledge;Lead;Lesion;leukemia;Light;Localized Disease;Malate Dehydrogenase;Malignant neoplasm of thyroid;Malignant Neoplasms;Mediating;member;Metabolic;Missense Mutation;Mitochondrial Proteins;Mixed Function Oxygenases;Modeling;Molecular;mouse model;mutant;Mutation;Neoplasms;neoplastic;Nuclear;Oncogenic;Operative Surgical Procedures;Oxygenases;Paraganglioma;Patients;Phenotype;Pheochromocytoma;Process;Production;Property;Protein Isoforms;Proteins;Quality of life;Reactive Oxygen Species;Renal Carcinoma;Renal Cell Carcinoma;Reporting;Research Project Grants;RNA;Role;small hairpin RNA;Somatic Mutation;Source;stem;stem cell biomarkers;stem cells;Structural Protein;Study models;Succinate Dehydrogenase;Succinates;Survival Rate;Syndrome;System;therapy development;Thyroid Gland;Time;Tissues;transcription factor;tumor;Tumor Promotion;tumorigenesis;United States;United States National Institutes of Health;Validation;Variant;Work

PROJECT_TITLE: Identification of enzymes inhibited by oncometabolites in Succinate Dehydrogenase mutant tumors


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Machine Learning and Artificial Intelligence;Multiple Sclerosis;Neurodegenerative;Neurosciences;Patient Safety;Precision Medicine

ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE The rapid expansion of approved treatments and the individual variation in treatment response have created a critical unmet need to develop individually tailored treatment strategy for the nearly 3 million persons with multiple sclerosis (MS) worldwide. The proposed study will address salient knowledge gaps in the MS clinical management due to the absence of randomized controlled trial evidence. To achieve the goal of generating robust real-world evidence to guide optimal treatment selection and patient outcomes at the point of care, we will apply novel computational methods such as machine learning to electronic health records (EHR) data. First, we will compare the effectiveness of commonly prescribed MS treatments using EHR data to correct for confounding bias. Second, we will identify patient clusters based on an individual’s MS treatment prescription pattern over time and compare the clinical outcomes among the patient clusters. Third, we will identify optimal MS treatment sequences that predict favorable treatment responses using EHR data and reinforcement learning. The proposed research will close knowledge gaps due to absent randomized controlled trial evidence and limited real-world evidence to guide optimal treatment selection and bring precision medicine closer to people with MS.

PI_NAMEs: XIA, ZONGQI  (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Address;Benchmarking;Chronic;Classification;Clinical;Clinical Data;Clinical Management;cohort;Collaborations;comorbidity;comparative effectiveness analysis;compare effectiveness;Computing Methodologies;cost;Data;Data Analyses;data registry;data warehouse;demographics;Disease;Effectiveness;efficacy clinical trial;Electronic Health Record;Ensure;Event;Favorable Clinical Outcome;Frequencies;Future;Goals;Healthcare Systems;improved;Individual;individual variation;individualized medicine;Knowledge;Learning;longitudinal, prospective study;Machine Learning;Maps;markov model;Medical center;meetings;Mission;Modeling;Multiple Sclerosis;multiple sclerosis patient;multiple sclerosis treatment;National Institute of Neurological Disorders and Stroke;Nervous System Disorder;Nervous System Physiology;non-compliance;novel;Observational Study;optimal treatments;Outcome;Patient Outcomes Assessments;patient registry;Patient-Focused Outcomes;Patients;Pattern;phenome;Phenotype;point of care;Population;Positioning Attribute;precision medicine;Probability;Productivity;Psychological reinforcement;randomized, clinical trials;Randomized, Controlled Trials;Recording of previous events;Registries;Relapse;Research;Selection for Treatments;Severities;Testing;Time;Time trend;transfer learning;Treatment Efficacy;Treatment Failure;treatment optimization;Treatment outcome;treatment response;treatment strategy;trial comparing;Universities;Validation

PROJECT_TITLE: Leveraging electronic health records to optimize treatment selection and response in multiple sclerosis

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]


NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Estrogen;Heart Disease;Menopause;Prevention;Women's Health Research

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: PROJECT NARRATIVE While cardiovascular disease (CVD) is the leading cause of death in men and women, substantial sex differences exist in disease prevalence and prognosis. Elevated myocardial stiffness is a precursor and a biological response to a spectrum of cardiovascular diseases and is highly likely to be affected by hormonal changes during menopause, but quantitative non-invasive in vivo measurements have not been realized clinically to make these measurements. In this project, we will develop a non-invasive magnetic resonance elastography (MRE) method that quantitatively measures myocardial stiffness and will use it to evaluate the influence of natural aging, sex, and menopause transition on myocardial stiffness.

PI_NAMEs: FORGHANIAN-ARANI, ARVIN  (contact)

PROGRAM_OFFICER_NAME: DANTHI, NARASIMHAN

PROJECT_TERMS: 3-Dimensional;Acceleration;Adoption;Affect;Age;age effect;Aging;Biological;Biological Markers;Biomechanics;Blood Tests;Breathing;Cardiac;cardiac magnetic resonance imaging;Cardiac Volume;Cardiovascular Diseases;cardiovascular disorder risk;Cause of Death;Clinical;clinical biomarkers;clinical examination;clinical imaging;critical period;Data;Development;Diagnostic;Diastole;Disease;disorder prevention;Dyspnea;Echocardiography;EFRAC;Enrollment;Evolution;Failure;Follicle Stimulating Hormone;follow-up;Functional disorder;Future;Goals;Heart;Heart failure;Hormonal Change;hospitalization rates;Image;imaging biomarker;improved;in vivo;Intervention;Left;Left Ventricular Ejection Fraction;Longitudinal Studies;Magnetic Resonance Elastography;Measurement;Measures;Mechanics;men;Menopausal Status;Menopause;Methods;Modeling;Monitor;Motion;Myocardial;Myocardial tissue;normal aging;Participant;patient population;Patients;Perimenopause;Phase;Pilot Projects;Postmenopause;Premenopause;preservation;pressure;Prevalence;prevent;Prevention;preventive intervention;Prognosis;quantitative imaging;Radial;reconstruction;reproductive;Resolution;respiratory;response;Risk;Risk Factors;routine imaging;Sampling;sex;sex as a biological variable;Sex Bias;Sex Differences;Shortness of Breath;Slice;Symptoms;System;Systole;Techniques;Technology;Testing;Therapeutic Trials;Time;tool;trend;Validation;Ventricular;volunteer;Woman

PROJECT_TITLE: Evaluating the natural evolution of myocardial stiffness in aging, sex differences, and through menopause transition in women, using a free-breathing magnetic resonance elastography approach

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


NIH_SPENDING_CATS: Chronic Obstructive Pulmonary Disease;Clinical Research;Data Science;Genetics;Lung;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine

PHR: Project Narrative In this application, we propose to use machine learning to construct COPD patient profiles integrating their clinical and genomic data to study COPD heterogeneity. We leverage these integrated profiles to identify biologically meaningful COPD subtypes and predict disease outcomes. Finally, we use network-based methodologies to identify the biological pathways connected to each subtype and gain a deeper understanding of the molecular underpinnings of COPD heterogeneity.

PI_NAMEs: MAIORINO, ENRICO  (contact)

PROGRAM_OFFICER_NAME: YE, JANE

PROJECT_TERMS: Affect;Agreement;Area;autoencoder;Biological;Biological Assay;Biological Process;Biology;career;Cause of Death;Characteristics;Chronic Bronchitis;Chronic Obstructive Pulmonary Disease;Classification;Clinical;clinical biomarkers;Clinical Data;Clinical Research;clinical subtypes;clinically significant;Cohort Studies;Collection;Data;data integration;deep learning;deep neural network;Development;dimension reduction;Discrimination;Disease;disease heterogeneity;Disease Management;Disease Outcome;Disease Progression;disorder subtype;Endogenous Factors;Environment;Environmental Risk Factor;epigenomics;Exogenous Factors;Frequencies;Future;Genes;Genetic;Genetic Markers;genomic data;Goals;Grouping;high dimensionality;improved;Individual;insight;Investigation;Joints;Knowledge;Link;Lung Diseases;Machine Learning;Measurement;medical schools;Medicine;meetings;member;Mentors;Methodology;Methods;Molecular;Molecular Conformation;molecular marker;Molecular Profiling;molecular subtypes;mortality;Multiomic Data;multiple omics;Network-based;neural network architecture;novel marker;Outcome;Pathogenesis;Pathway interactions;Patients;Pattern;personalized medicine;personalized therapeutic;Phenotype;phenotypic data;Population;precision medicine;predict clinical outcome;Process;profiles in patients;prognostic model;programs;Property;protein protein interaction;Public Health;Pulmonary Emphysema;pulmonary function;Research;Research Personnel;Respiratory Disease;Sampling;Science;skills;specific biomarkers;Spirometry;statistics;Structure of parenchyma of lung;Time;Training;Training Programs;transcription factor;transcriptomics;Work

PROJECT_TITLE: Linking endotype and phenotype to understand COPD heterogeneity via deep learning and network science


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Gene Therapy;Genetics;Hematology;Nanotechnology;Orphan Drug;Rare Diseases;Sickle Cell Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_DEPT: BIOMEDICAL ENGINEERING

PHR: Project Narrative CRISPR/cas9 gene editing has shown great promise for the treatment of genetic hematological diseases. Here we propose to develop a novel gene editing platform that combines nanotechnology and synthetic biology approaches for precise in vivo gene editing of HSPCs in the bone marrow. The success of this project has the potential to provide an effective and low-cost therapy for hematological diseases.

PI_NAMEs: TONG, SHENG  (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: adaptive immunity;Adult;Allogenic;Autologous;Autologous Transplantation;Back;Basic Science;beta Globin;beta Thalassemia;Binding Sites;Blood Vessels;Bone Marrow;Bone Marrow Cells;Bone Marrow Purging;Cell Therapy;Cells;Chromosome Mapping;clinical application;clinical translation;Clinical Treatment;Clustered Regularly Interspaced Short Palindromic Repeats;complement system;cost;CRISPR/Cas technology;curative treatments;delivery vehicle;design;Disease;DNA;DNA cassette;DNA Sequence;DNA Sequence Alteration;Endothelium;Engraftment;Extravasation;Face;Femur;Future;gene correction;Gene Delivery;gene editing technology;Gene Mutation;gene-editing approach;Genes;Genetic;genotoxicity;Guide RNA;Hematological Disease;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Hemoglobinopathies;Human;Immunologics;In Situ;in vivo;Infusion procedures;Insect Viruses;intravenous injection;lipid nanoparticle;magnetic field;Magnetic nanoparticles;Magnetism;Mammalian Cell;Mediating;Messenger RNA;Methods;MicroRNAs;mouse model;mRNA Translation;multidisciplinary;Mus;Mutation;Myelogenous;nanomedicine;nanoparticle;Nanotechnology;novel;nuclease;Patients;Permeability;Population;Post-Translational Regulation;preclinical study;Regulatory Element;Risk;self-renewal;Sickle Cell Anemia;Site;Specificity;stem cell biology;stem cells;success;synthetic biology;System;targeted delivery;Techniques;Therapeutic;therapeutic target;tool;Toxic effect;Transfection;transgene delivery;Translation Initiation;translational potential;Transplantation;Untranslated RNA;vector;Viral Vector

PROJECT_TITLE: Precise in vivo gene editing of HSPC for the treatment of genetic hematologic diseases

STUDY_SECTION: GDD

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


NIH_SPENDING_CATS: Antimicrobial Resistance;Clinical Research;Genetics;Infectious Diseases;Malaria;Rare Diseases;Vector-Borne Diseases

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE: Leveraging our extensive infrastructure and ongoing research activities in Uganda, we will characterize emerging antimalarial resistance at field sites across Uganda. We will use molecular, parasitological and epidemiological approaches to better understand the extent and origins of drug resistance, the genotypes that contribute to resistance, and the epidemiological factors that facilitate the evolution of resistant parasites.

PI_NAMEs: CONRAD, MELISSA D (contact)

PROGRAM_OFFICER_NAME: RAO, MALLA R

PROJECT_TERMS: Address;Africa;Age;Anti-malarial drug resistance;Anti-malarials;Artemisinins;Automobile Driving;Biological Assay;Blood;candidate validation;Cessation of life;Clinical;Collection;Combined Modality Therapy;Communication;Country;CRISPR/Cas technology;deep sequencing;Detection;Drug Exposure;Drug resistance;Epidemiologic Factors;Epidemiology;Evolution;fitness;Fright;Genetic;Genetic Polymorphism;Genotype;Geography;Goals;Growth;Hot Spot;Household;Immunity;improved;In Vitro;Incidence;Individual;Infection;Infrastructure;Intervention;Laboratories;Malaria;Maps;Mediating;Metadata;Modernization;Molecular;Molecular Epidemiology;molecular marker;Mutation;novel;novel therapeutics;Parasite resistance;Parasites;Parasitology;Pharmaceutical Preparations;Phenotype;Plasmodium falciparum;Policies;Policy Maker;Population;Population Genetics;Positioning Attribute;Predisposition;Prevalence;Public Health;Reporting;Research Activity;Resistance;Resolution;response;Rwanda;Site;Testing;Time;transmission process;trend;Uganda;Urbanicity;Validation

PROJECT_TITLE: Surveillance to track and characterize antimalarial resistance trends in Ugandan Plasmodium falciparum parasites (STARTUP)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIB-J(90)]


NIH_SPENDING_CATS: Aging;Brain Disorders;Cerebrovascular;Machine Learning and Artificial Intelligence;Neurosciences;Stroke

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: SPAN is a randomized, placebo-controlled, blinded, multi-laboratory trial using state-of-the-art experimental design and rigor to successfully reduce or eliminate common sources of bias in choosing treatments for evaluation in clinical studies. The applicant PI and research team—the SPAN Coordinating Center (CC)— created and implemented novel solutions to several key barriers that impede pre-clinical network implementation, resulting in a highly successful, multi-site network for testing putative cerebroprotectants in animal stroke models that include equal numbers of females and males and co-morbidities such as aging, hypertension and hyperglycemia. This renewal application will allow the SPAN CC to continue significant improvement and advancement of preclinical development by implementing critical technical innovations, including novel assessment tools using machine learning, and continue our track record of successful enrollment and technical innovation, providing a model for pre-clinical networks in other disease areas.

PI_NAMEs: LYDEN, PATRICK D (contact)

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Address;Aging;Animal Model;Animals;Area;arm;Artificial Intelligence;Assessment tool;Award;Behavior;Behavior assessment;behavior test;Behavioral;behavioral outcome;blind;Blinded;Blood coagulation;Certification;Clinical Research;Clinical Trials;clinically relevant;Communication;comorbidity;Data;Databases;design;digital;Disease;Drug Compounding;Elements;Enrollment;Evaluation;experience;Experimental Designs;falls;Female;Funding;Futility;Future;Goals;Histologic;Hyperglycemia;Hypertension;Image;improved;improved outcome;Individual;Infrastructure;innovation;Intervention;invention;Ischemic Stroke;Laboratories;Lead;Lesion;Machine Learning;machine learning algorithm;Magnetic Resonance Imaging;male;meetings;Methods;Mind;Modeling;Modernization;Monitor;morphometry;MRI Scans;Mus;National Institute of Neurological Disorders and Stroke;novel;Operative Surgical Procedures;Outcome;Outcome Assessment;Phase;phase 2 testing;Placebo Control;power analysis;pre-clinical;pre-clinical assessment;Pre-Clinical Model;preclinical development;Preclinical Testing;primary outcome;Procedures;Process;Production;Protocols documentation;Randomized;Rattus;Reperfusion Therapy;Reporting;repository;Reproducibility;Research;Research Personnel;Review Literature;secondary outcome;Secure;Site;Site Visit;Source;Specific qualifier value;Stroke;stroke model;stroke therapy;success;Support System;Surgeon;System;Testing;Therapeutic;therapy design;thrombolysis;Time;tool;Training;Uncertainty;United States National Institutes of Health;Update

PROJECT_TITLE: The NIH SPAN Coordinating Center


NIH_SPENDING_CATS: Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Immunotherapy;Orphan Drug;Precision Medicine;Rare Diseases

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Existing analysis of HNSCC cancer tissues obtained by core biopsy is limited in many aspects. We have developed a new immune and cancer cell profiling technology based on cellular immunocycling. Using fine needle aspirates (FNA) rather than more invasive core biopsies, this method allows frequent and serial profiling on the composition of the tumor microenvironment in HNSCC patients undergoing immunotherapy.

PI_NAMEs: PAI, SARA ISABEL;WEISSLEDER, MD, PHD, RALPH  (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Address;anti-PD-1;Antibodies;Archives;Artificial Intelligence;B-Lymphocytes;Biological Markers;biomarker discovery;biomarker validation;Biopsy;Biopsy Specimen;cancer cell;Cells;Certification;Chemistry;chemotherapy;Clinical;clinical application;Clinical Laboratory Improvement Amendments;clinical predictors;companion diagnostics;Consumption;Core Biopsy;cost;Diagnostic;Emerging Technologies;Engineering;Evaluation;Evolution;experimental study;Fine needle aspiration biopsy;Fresh Tissue;Goals;Head and Neck Squamous Cell Carcinoma;Human;Image Guided Biopsy;Immune;Immune response;Immunotherapeutic agent;Immunotherapy;innovation;Laboratories;Malignant Neoplasms;Methods;Modification;molecular marker;Morbidity - disease rate;mouse model;Needles;novel;Pathologist;Patients;Physiologic Monitoring;predictive marker;programmed cell death ligand 1;prospective;Quality Control;Recurrence;Research;response;response biomarker;Sampling;Sedation procedure;single-cell RNA sequencing;Site;Specimen;Stains;System;T-Lymphocyte;Technology;Testing;therapy outcome;Time;Tissue Harvesting;Tissues;Training;Translating;translational goal;Treatment Efficacy;Treatment Protocols;tumor;tumor microenvironment;United States Food and Drug Administration;Validation

PROJECT_TITLE: FAST-FNA immune cell profiling in HNSCC

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


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Immunization;Infectious Diseases;Malaria;Malaria Vaccine;Orphan Drug;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE Malaria kills hundreds of thousands and sickens hundreds of millions of people globally each year. This project will use cutting edge molecular and immunological analyses of samples from clinical trials with live attenuated parasite vaccines to identify new vaccine antigens and characterize vaccine induced antibody and cellular immune responses. The materials and knowledge from this project can aid malaria vaccine development.

PI_NAMEs: STUART, KENNETH D (contact)

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: adaptive immune response;analytical tool;Antibodies;Antibody Response;Antibody Specificity;Antigen Presentation;Antigen Receptors;antigen-specific T cells;Antigens;Attenuated;B-Cell Antigen Receptor;B-Lymphocytes;Base Sequence;Benchmarking;Bioinformatics;Biological Assay;biophysical properties;Biophysics;Blood;Cell Physiology;Cells;Characteristics;Clinical Trials;Complex;cytokine;Cytometry;Data;data portal;data sharing;Epitopes;Erythrocytes;experience;family structure;Gene Expression;Gene Expression Profile;Genes;Goals;Immune;immune function;Immune response;Immunity;Immunologics;Immunology;In Vitro;Infection;Informatics;Infrastructure;Innate Immune Response;insight;Joints;Kinetics;Knowledge;Link;Liver;longitudinal analysis;Malaria;Malaria Vaccines;Mediating;Metadata;Methods;Molecular;Monoclonal Antibodies;multiple omics;novel;novel vaccines;Parasites;Peptide/MHC Complex;Peptides;Persons;Phenotype;Plasmodium falciparum;Population;Process;protein expression;prototype;Resources;response;Role;Sampling;Sequence Analysis;single cell sequencing;Sorting;Specificity;Sporozoites;Stains;System;T Chain;T-cell receptor repertoire;T-Lymphocyte;transcriptomics;United States National Institutes of Health;Vaccination;Vaccine Antigen;vaccine development;vaccine efficacy;vaccine evaluation;vaccine immunogenicity;vaccine-induced antibodies;Vaccines;Yeasts

PROJECT_TITLE: Collective Responses to Malaria Vaccination


NIH_SPENDING_CATS: Brain Disorders;Down Syndrome;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_DEPT: PEDIATRICS

PHR: Narrative Down Syndrome is primarily caused by trisomy of chromosome 21, resulting in an extra copy of over 200 genes and significant intellectual and developmental disability. Generating translational models and identifying the brain cell type specific contribution to Down Syndrome pathophysiology has been difficult and has hampered development and screening of new treatments. This project is relevant to the NIH’s mission to enhance life and reduce disability, aiming to understand how human microglia contribute to the neurodevelopmental pathogenesis of Down Syndrome with a goal of identifying novel treatment targets and screening methodologies.

PI_NAMEs: COUFAL, NICOLE GABRIELE (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: 3-Dimensional;Adolescent;Affect;amyloid pathology;Architecture;astrogliosis;ATAC-seq;Behavior assessment;behavior test;Behavioral;behavioral phenotyping;Biogenesis;Brain;brain cell;Cell Respiration;cell type;Cerebrum;Child;ChIP-seq;Chromosome 21;Chromosomes;clinical predictors;Coculture Techniques;Cognition;Cognitive deficits;cognitive testing;comparison control;Complex;cytokine;Data;Defect;Dendritic Spines;density;Development;disability;Down's Syndrome;Drug Screening;Engraftment;Environment;Epigenetic Process;Exhibits;Functional disorder;Gene Expression;Genes;Genetic;Genetic Transcription;genome-wide;Genomics;Goals;Heterogeneity;Human;human induced pluripotent stem cells;human model;human stem cell-derived;Hypertrophy;Immune System Diseases;Immunologics;Impaired cognition;improved outcome;In Vitro;in vivo;Individual;Inflammatory;innovation;Intellectual functioning disability;Interferons;Knowledge;Learning;Life;life span;Maps;Measurement;Memory;Mental disorders;Methodology;Methods;Microglia;migration;Mission;Mitochondria;Modeling;Molecular;Morphology;mouse model;Mus;nerve stem cell;Neurodegenerative Disorders;neurodevelopment;Neurodevelopmental Deficit;neuroimmunology;Neurons;neuropathology;new therapeutic target;Nitrogen;novel;novel therapeutic intervention;novel therapeutics;Organoids;Orthologous Gene;Outcome;Oxygen;Pathogenesis;Pathologic;Pathology;Patients;Peripheral;Phagocytosis;Phenotype;pre-clinical;prevent;Regulation;response;screening;Short-Term Memory;single-cell RNA sequencing;stem cells;Stimulus;Synaptosomes;System;Testing;Therapeutic;therapeutic target;Thick;transcriptome sequencing;transcriptomics;translational impact;translational model;Trisomy;United States;United States National Institutes of Health;Vertebral column;vocalization;Xenograft Model;young adult

PROJECT_TITLE: Microglial contribution to Down Syndrome Neuropathology

STUDY_SECTION: CMBG

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


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

ORG_CITY: TAMPA

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

PHR: PROJECT NARRATIVE Microglial cells are the resident immune cell of the brain and are responsible for the immunological defense of the central nervous system against invading pathogens, brain injury, and amyloid deposition. The studies herein are designed to investigate a novel mechanism in regulating neuroinflammation in response to β-amyloid, a causative factor in Alzheimer’s Disease (AD). The proposed research will lead to a more comprehensive understanding of the establishment of neuroinflammation in aging and AD, and approaches to manipulate this pathway in the treatment of neurodegenerative diseases.

PI_NAMEs: HECKMANN, BRADLEE L (contact)

PROGRAM_OFFICER_NAME: MCGAVERN, LINDA

PROJECT_TERMS: abeta deposition;Address;age related;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid beta-Protein;Amyloid deposition;Animal Model;Animals;Apoptotic;Autophagocytosis;Biological Assay;biological systems;Brain;brain cell;Brain Injuries;Cell Death;Cells;Cellular biology;Central Nervous System;Cessation of life;Complex;cytokine;Data;Deposition;design;Development;Disease;Endocytosis;Endocytosis Pathway;Endosomes;Experimental Designs;Genetic;Genetic Drift;glial activation;Human;Immune;immune activation;immune system function;Immunologics;Impairment;improved;in vivo;infancy;Inflammasome;Inflammation;Inflammatory;Invaded;Investigation;Link;Macrophage;Measurable;Memory;Memory impairment;Methodology;Microglia;Molecular;Mus;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;neuron loss;neurotoxic;novel;old mice;Onset of illness;pathogen;Pathology;Pathway interactions;Phagocytosis;Physiological;Play;Process;Production;programs;Proteins;Reactive Oxygen Species;receptor;receptor recycling;Recycling;Regulation;Research;response;Role;Severity of illness;Signal Transduction;tau Proteins;tau-1;therapeutic development;therapeutic target;TLR4 gene;trafficking;TREM2 gene;WD Repeat

PROJECT_TITLE: Regulation of LC3-associated endocytosis and neuroinflammation

STUDY_SECTION: NOMD

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


NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Cardiovascular;Clinical Research;Heart Disease;Hematology;Kidney Disease

ORG_CITY: BALTIMORE

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: PROJECT NARRATIVE Medical devices that use blood pumps, for example on pump cardiopulmonary bypass (CPB) leads to the destruction of red blood cells (RBCs) when used over long duration (>4 hour). The hemoglobin released into circulation as a result of RBC damage can cause organ toxicity, for example acute kidney injury in at risk patients. These complications can extend patient hospital stays at a cost of more than $9 billion/year and lead to 300,000 avoidable deaths. Therefore, developing methods to remove hemoglobin and its degradation products in patients undergoing procedures requiring medical device use, such cardiac surgery with on pump CPB will improve individuals outcomes and overall public health.

PI_NAMEs: BUEHLER, PAUL WERNER (contact);CABRALES, PEDRO ;IRWIN, DAVID CHARLES;PALMER, ANDRE FRANCIS

PROGRAM_OFFICER_NAME: AGRAWAL, NITIN

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Affinity;Animal Model;Animals;apohemoglobin;Attenuated;Binding;Binding Proteins;Binding Sites;Biological Assay;Biological Markers;Biomedical Engineering;blood pump;Brain;Cardiac;Cardiac Output;Cardiac Surgery procedures;Cardiopulmonary Bypass;cell injury;Cells;Cessation of life;Chemicals;Circulation;Clinical;clinically relevant;Complex;Complication;cost;cost estimate;Cytolysis;Data;design;dimer;Dimerization;Dose;Drug Metabolic Detoxication;Drug or chemical Tissue Distribution;Effectiveness;Engineering;Erythrocytes;experience;Extracorporeal Membrane Oxygenation;Fractionation;Functional disorder;Goals;Hamsters;Haptoglobins;Health Care Costs;Heart;heart function;Heme;hemodynamics;Hemoglobin;Hemoglobin concentration result;Hemolysis;Hemolysis Induction;Hemopexin;Hospitalization;Hour;Human;improved;In Vitro;in vivo;Individual;individual patient;Injury to Kidney;instrument;Intestines;Iron;Kidney;Kinetics;large scale production;Length of Stay;Ligands;Lung;lung injury;Macrophage;Medical;Medical Device;Methods;Microvascular Permeability;Modeling;Monitor;monocyte;Morbidity - disease rate;mortality;mortality risk;novel;novel therapeutics;Operative Surgical Procedures;Organ;organ injury;Outcome;Paste substance;Patients;Plasma;prevent;Procedures;Process;prospective;protein complex;Proteins;Proteolysis;proteostasis;Public Health;pulmonary function;Pump;Qualifying;Rattus;Reaction;Renal function;response;Risk;Sampling;Secure;Self-Help Devices;Severities;Supportive care;System;Testing;Therapeutic;Therapeutic Intervention;Therapeutic Uses;Toxic effect;Toxin;Transferrin;urinary;Urine;Ventricular

PROJECT_TITLE: Bioengineering a novel therapeutic protein complex to minimize the effects of medical device induced hemolysis


NIH_SPENDING_CATS: Aging;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Genetic Testing;Genetics;Precision Medicine;Prevention;Women's Health Research

PHR: NARRATIVE Women with atypical hyperplasia (AH) have increased risk of breast cancer (BC). Toward the goal of improving cancer prevention for these women, this research will identify biomarkers from breast biopsy tissues that will improve individualized risk prediction and help to determine which women will personally benefit from tamoxifen.

PI_NAMEs: DEGNIM, AMY C (contact);RADISKY, DEREK C

PROGRAM_OFFICER_NAME: HECKMAN-STODDARD, BRANDY

PROJECT_TERMS: Address;African American Women;Atypical hyperplasia;Atypical Hyperplasia of the Breast;Benign;Biological;Biological Markers;biomarker discovery;biomarker evaluation;biomarker identification;Biopsy;Breast;Breast biopsy;Breast Cancer Prevention;Breast Cancer Prevention Trial;Breast Cancer Risk Factor;Breast Carcinogenesis;Breast Diseases;breast imaging;breast lesion;cancer prevention;Clinic;Clinical;Clinical Trials;cohort;Computing Methodologies;Diagnosis;early detection biomarkers;Effectiveness;Event;experience;Formulation;Gel;Gene Expression Profiling;genetic signature;Goals;high risk;High Risk Woman;Histologic;Hormonal;hormone therapy;improved;Incidence;Individual;individual response;individualized prevention;innovation;insight;Investments;Link;Malignant Breast Neoplasm;Mammary Gland Parenchyma;Mammographic Density;Measures;Methods;Molecular;nano-string;non-invasive imaging;novel;novel marker;Oral;personalized decision;personalized risk prediction;predicting response;predictive marker;Prevention;Prevention approach;Prevention strategy;Prevention therapy;Prevention trial;primary endpoint;randomized placebo controlled study;randomized, clinical trials;Research;Resources;response;response biomarker;Retrospective cohort;Risk;risk prediction;risk prediction model;Risk Reduction;RNA;Sampling;Sampling Studies;side effect;Tamoxifen;Tissues;tool;Toxic effect;Transcript;translational study;treatment duration;Universities;uptake;Woman;women's prevention;Women's trial;Work

PROJECT_TITLE: Biomarkers to Improve Targeting of Breast Cancer Prevention in Women with Atypical Hyperplasia

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_CITY: PORTLAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Exposure to cues associated with cocaine use can trigger relapse in recovering cocaine users, even after long periods of abstinence. The proposed experiments will test the role of retinoic acid signaling in the synaptic plasticity underlying this persistent vulnerability to cue-induced relapse. By focusing on retinoic acid signaling - a pathway that has only recently been implicated in cocaine addiction - our work has the potential to identify novel targets for therapies aimed at preventing relapse and prolonging abstinence.

PI_NAMEs: WOLF, MARINA ELIZABETH (contact)

PROGRAM_OFFICER_NAME: TSAI, SHANG-YI ANNE

PROJECT_TERMS: Abstinence;Acute;Area;Attenuated;Brain;Brain region;cell cortex;Cells;Cocaine;cocaine craving;cocaine cue;Cocaine Dependence;cocaine seeking;cocaine self-administration;cocaine use;Cocaine Users;Cocaine withdrawal;Coculture Techniques;craving;Cue-induced relapse;Cues;Data;Development;Disinhibition;Enterobacteria phage P1 Cre recombinase;Enzymes;Exhibits;experimental study;Exposure to;falls;Fiber;Glutamates;Hippocampus;Home;Human;Incubated;knock-down;Lead;Link;Maintenance;Mediating;Modeling;Neurons;new therapeutic target;novel;Nucleus Accumbens;patch clamp;Pathway interactions;Permeability;Pharmaceutical Preparations;Phase;Photometry;Population;prolonged abstinence;Proteins;Rat Transgene;Rattus;receptor;Relapse;relapse prevention;response;Role;Saline;Signal Transduction;Synapses;Synaptic plasticity;Synaptic Transmission;synthetic enzyme;Testing;tool;Translations;transmission process;Tretinoin;Withdrawal;Work

PROJECT_TITLE: Retinoic acid, homeostatic plasticity and cocaine craving

STUDY_SECTION: MNPS

STUDY_SECTION_NAME: Molecular Neuropharmacology and Signaling Study Section[MNPS]


NIH_SPENDING_CATS: Genetics

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Project Narrative Nearly all phenotypes, from height and weight to disease susceptibility, result from a complex interplay between genes and the environment. This project aims to illuminate basic rules acting to integrate environmental and genetic signals in the production of the phenotype. Thus, the proposed research is relevant to the part of NIH's mission that pertains to developing fundamental knowledge that will help to reduce the prevalence of human disease.

PI_NAMEs: BRISSON, JENNIFER A (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Address;Aphids;asexual;Bypass;Complex;Cues;Developmental Process;dimorphism;Disease;Disease susceptibility;Environment;Epigenetic Process;Evolution;Exhibits;experimental study;fascinate;Female;Follistatin;Genes;Genetic;Genetic Polymorphism;genomic locus;Health;Height;Horizontal Gene Transfer;Hormones;Human;human disease;innovation;insight;Knowledge;Life;male;Mission;Modeling;Molecular;Morphology;Nature;Organism;paralogous gene;Phenotype;Pisum sativum;Plants;Prevalence;Process;Production;programs;recruit;Research;Role;Signal Transduction;Testing;Textbooks;trait;United States National Institutes of Health;Variant;Weight;Wing;Women's study

PROJECT_TITLE: Molecular Mechanisms and Evolution of Phenotypic Plasticity

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]