NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetic Testing;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Narrative The development and validation of predictive models is a critical step toward improving strategies for an early diagnosis of sporadic frontotemporal dementia (FTD) and other neurodegenerative diseases and improving strategies for personalized treatment. The goal of this proposal is to develop novel imaging genetic biomarkers that can help clinicians with an early and accurate diagnosis and prognosis of sporadic FTD. This project is highly relevant to the NIA’s mission because it supports the conduct of genetic, imaging, and clinical aging research and fosters the development of a clinical research scientist in aging.

PI_NAMEs: BROCE-DIAZ, IRIS J (contact)

PROGRAM_OFFICER_NAME: ROVESCALLI, ALESSANDRA C

PROJECT_TERMS: Acceleration;accurate diagnosis;Age;Age of Onset;age related;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Atrophic;Behavioral;Biological;Biological Markers;biomarker development;Biometry;Brain Mapping;California;Cardiovascular Diseases;Cardiovascular system;career;Classification;Clinical;clinical development;clinical heterogeneity;Clinical Research;clinical subtypes;Clinical Trials;Clinical Trials Design;Cognitive aging;cohort;Complex;Computer Models;Data;Data Set;Dementia;dementia risk;Development;Diagnosis;Diagnostic;diagnostic tool;Differential Diagnosis;Discriminant Analysis;Disease;Early Diagnosis;Environment;Epidemiologist;Epidemiology;experience;Fostering;frontal lobe;Frontotemporal Dementia;Frontotemporal Lobar Degenerations;Genes;Genetic;Genetic Markers;Genetic Models;Genetic Research;Genetic Risk;genetic variant;Genotype;Goals;hazard;high risk;Image;imaging biomarker;imaging genetics;Immune;Immunologics;improved;Incidence;Individual;Inherited;innovation;International;Iris;Knowledge;Language;Machine Learning;Magnetic Resonance Imaging;Mediating;Memory;Mentored Research Scientist Development Award;Mentors;Mentorship;Methodology;Methods;Mission;Modeling;multimodal data;Multimodal Imaging;multimodality;Nerve Degeneration;Neurodegenerative Disorders;neuroimaging;Neurologist;neuropathology;novel;Outcome;Pathway interactions;patient oriented;patient subsets;Patients;Pattern;Performance;personalized medicine;personalized strategies;Phenotype;pleiotropism;polygenic risk score;population based;Postdoctoral Fellow;predictive marker;predictive modeling;professor;Prognosis;prognostic tool;programs;recruit;Research;Research Methodology;Research Project Grants;Risk;risk prediction;Role;San Francisco;Scientist;skills;Social Behavior;statistics;Stratification;Subgroup;symptomatology;targeted treatment;tau Proteins;Tauopathies;Techniques;Temporal Lobe;Therapeutic;Therapeutic Clinical Trial;Time;tool;Training;Translating;United States National Institutes of Health;Universities;Validation;Work

PROJECT_TITLE: Novel imaging genetic biomarkers for sporadic frontotemporal dementia through machine learning

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Clinical and Translational Research of Aging Study Section[NIA -T]


ADMINISTERING_IC: DC

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

ORG_CITY: STANFORD

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OTOLARYNGOLOGY

ORG_FIPS: US

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: Research is advancing the field of Otolaryngology–Head and Neck Surgery. Here, we have designed a research training program to train the next generation of physician-scientists in areas aligned with NIDCD missions, to ultimately improve human health by combining scientific discovery with clinical care.

PI_NAMEs: CHENG, ALAN GI-LUN (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: Advisory Committees;Aging;Applications Grants;Area;Association of American Medical Colleges;Award;Basic Science;Budgets;career;career development;Clinical;clinical care;Clinical Research;Collaborations;Dedications;design;Diagnosis;Disease;Doctor of Philosophy;Environment;Equilibrium;equity, diversity, and inclusion;experience;Faculty;Fellowship;Funding;Future;gender diversity;Goals;graduate medical education;hands on research;Head and Neck Surgery;Health;health communication;Healthcare;Hearing;Human;improved;Individual;Infrastructure;innovation;interest;Journals;Language;medical schools;Medical Students;Medicine;Mentors;Mentorship;Mission;National Institute on Deafness and Other Communication Disorders;next generation;Operative Surgical Procedures;Otolaryngology;Outcome;Output;Patient Care;Patients;Philosophy;Physicians;Positioning Attribute;programs;racial diversity;recruit;Reporting;Research;Research Activity;Research Personnel;Research Training;Residencies;Resources;Schedule;Schools;Science;Scientist;Smell Perception;Speech;Structure;Surgeon;Surveys;Taste Perception;Time;Training;Training Programs;Translating;Translational Research;trend;United States National Institutes of Health;Universities;Voice;working group

PROJECT_TITLE: Stanford Clinician Scientist Training Program


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Aging

ORG_CITY: ROCHESTER

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: Tendon experiences substantial age-related impairments in structure, function, and healing capacity. The mechanisms that initiate these age-related disruptions are unknown and there are currently no therapeutic approaches to retain or restore tendon health through the lifespan. Here, we will define the multi-scale signature of tendon aging and define the efficacy of partial reprogramming to maintain and rescue tendon homeostasis and healing capacity in aged mice.

PI_NAMEs: LOISELLE, ALAYNA  (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Address;Age;Age Months;age related;Age related pathologies;age-related disease;aged;Aging;Anabolism;Apoptosis;ATAC-seq;Attenuated;Automobile Driving;c-myc Genes;cell age;Cell Communication;Cell Death;cell dedifferentiation;Cell Density;Cell Physiology;Cells;Cellularity;Cessation of life;Cues;Data;Drops;efficacy evaluation;Elderly;Environment;Epigenetic Process;experience;Extracellular Matrix;Flexor;functional plasticity;functional restoration;Genomics;Goals;healing;Health;Heterogeneity;Histologic;Homeostasis;Impaired healing;Impairment;improved;Inflammatory;Injury;juvenile animal;life span;Locomotion;Mechanics;middle age;Modeling;Modification;Molecular;Morphology;Mus;normal aging;novel strategies;novel therapeutics;old mice;Pathway interactions;Pattern;Periodicity;Phase;Phenotype;Physiological;pluripotency;Population;preservation;prevent;Production;programs;proteostasis;proteostasis loss;Quality of life;Rejuvenation;reparative capacity;response;Role;single-cell RNA sequencing;skeletal;Spontaneous Rupture;Structure;Tendon Injuries;Tendon structure;Testing;Therapeutic;therapeutic development;Tissues

PROJECT_TITLE: Age-related mechanisms of altered tendon structure and function


ORG_DEPT: PHARMACOLOGY

PHR: Project Narrative Effective therapeutic strategies for cartilage degeneration are urgently needed, and our preliminary data sug- gest differential roles of Piezo1 and Piezo2 channels in chondrocyte death and cartilage remodeling. We will use cutting-edge engineering and physiology approaches to identify the joint injury and exercise effect on un- derlying mechanisms of Piezo1/2-mediated cartilage homeostasis and degeneration. Our successful outcome will be useful in understanding cartilage pathology and in future therapeutic strategies for cartilage disorders, including osteoarthritis.

PI_NAMEs: LEE, WHASIL  (contact)

PROJECT_TERMS: aggrecan;American;anterior cruciate ligament injury;Area;Arthritis;arthropathies;articular cartilage;Atomic Force Microscopy;Biological Assay;Biological Markers;Cartilage;cartilage degradation;Cartilage Diseases;cartilage regeneration;Cells;Cessation of life;Chondrocytes;comparison control;Cultured Cells;Custom;Data;Degenerative polyarthritis;Devices;Disease;Engineering;Exercise;Exhibits;Extracellular Matrix;Female;Femur;Future;Gene Expression Regulation;Genes;Health;Homeostasis;Human;human disease;Image;immunocytochemistry;Immunohistochemistry;In Situ;In Vitro;Injury;insight;joint injury;Joints;Knee Injuries;Knockout Mice;Knowledge;male;mechanical load;mechanical signal;Mechanics;mechanotransduction;Mediating;Metabolic;Metabolism;Methods;Microscope;MMP3 gene;Modeling;Modulus;Monitor;mouse model;multidisciplinary;Mus;Natural regeneration;Outcome;Pathology;Pattern;Peptides;Physiology;Piezo 1 ion channel;Piezo 2 ion channel;Play;postmitotic;Predisposition;prevent;programs;Property;Reporting;resilience;response;Role;Running;Severities;Signal Transduction;System;Testing;Therapeutic;therapeutically effective;Thick;Tissues;Weight-Bearing state

PROJECT_TITLE: Piezo1 and Piezo2-dependent cartilage health and disease

STUDY_SECTION: SBSR

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


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Genetics

ORG_CITY: KANSAS CITY

ORG_NAME: STOWERS INSTITUTE FOR MEDICAL RESEARCH

ORG_STATE: MO

PHR: PROJECT NARRATIVE The zebrafish has proven to be a powerful disease model for various disorders, including metabolic disorders, cancer, and neurodegeneration, as well as a model for development and congenital defects. Organism-based meetings like the zebrafish meeting are essential to disseminate novel organism- specific technologies, to initiate collaborations, and to develop future scientific strategies critical for the field. This proposal seeks support for five future conferences in a successful series initiated in 1994, but in a new hybrid format that combines in-person and virtual attendance and thus allows broader participation.

PI_NAMEs: PIOTROWSKI, TATJANA  (contact)

PROGRAM_OFFICER_NAME: TOYAMA, REIKO

PROJECT_TERMS: 3-Dimensional;Aging;Alleles;American;Asia;Award;Bar Codes;Biological Models;Canada;Cancer Model;career;Cells;Cementation;Chemicals;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Communicable Diseases;Communication;Communities;Congenital Abnormality;cost;Country;COVID-19 pandemic;CRISPR/Cas technology;Data;demographics;Development;developmental disease;Disease;disease model;Dissection;Economics;Ensure;Environment;Epitopes;Europe;European;Faculty;Financial Support;forging;Fostering;Funding;Future;Gender;Generations;Genes;Genetic;genetic analysis;genome editing;Geographic Locations;Geography;Goals;graduate student;Grant;Growth;Homeostasis;Housing;Human;human disease;human model;Hybrids;imaging modality;Inflammatory;insertion/deletion mutation;International;Japan;Journals;Knowledge;Laboratories;Location;Malignant Neoplasms;Maps;meetings;Mental disorders;Metabolic Diseases;Metabolism;Methodology;Methods;model development;model organism;Modeling;Molecular;Mutation;Natural regeneration;Nerve Degeneration;neural circuit;new technology;novel;optogenetics;Organ;Organism;originality;Participant;Pathway interactions;Persons;Physiology;Poland;Postdoctoral Fellow;Price;professor;Proteins;Race;Research;Research Personnel;research study;Research Technics;Resolution;Resources;reverse genetics;Rotation;Science;Scientist;screening;senior faculty;Series;Societies;Students;success;symposium;Talents;Technology;Therapeutic Agents;Time;Tissues;tool;Transgenic Organisms;Travel;Underrepresented Populations;United States National Institutes of Health;virtual;virtual technology;Visualization;Zebrafish;zebrafish genome

PROJECT_TITLE: International Zebrafish Conference

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Developmental Biology Study Section[CHHD-C]


ADMINISTERING_IC: AT

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Depression;Eating Disorders;Mental Health;Mental Illness;Nutrition;Obesity

ORG_CITY: NEW YORK

ORG_DEPT: PSYCHOLOGY

ORG_NAME: YESHIVA UNIVERSITY

PHR: PROJECT NARRATIVE I propose to develop a novel digital treatment, Mindfulness Meditation-enhanced Cognitive Behavioral Therapy (CBT-MM), that integrates MM and CBT for the treatment of Binge Eating Disorder (BED) to target the two important mechanisms in the development and maintenance of BED: dietary over-restriction and emotion dysregulation. The current K23 proposal involves developing digital CBT-MM for BED and conducting a pilot randomized control trial to evaluate its feasibility, acceptability, and within-group changes from pre-to post treatment on indices of: binge eating remission, binge eating frequency, weight, quality of life, depressive symptoms, emotion dysregulation, dietary over-restriction, and trait mindfulness. This innovative research project has the potential to advance research on mindfulness-based treatment for eating disorders.

PI_NAMEs: SALA, MARGARITA  (contact)

PROGRAM_OFFICER_NAME: MUDD, LANAY MARIE

PROJECT_TERMS: acceptability and feasibility;Address;Affect;Aftercare;American;Area;Award;Behavioral;Benchmarking;Binge Eating;Binge eating disorder;career;Clinical;cognitive enhancement;Cognitive Therapy;Combined Modality Therapy;comparative efficacy;Conduct Clinical Trials;cost;depressive symptoms;Development;dietary;digital;digital delivery;digital treatment;Disease;Disease remission;Eating;Eating Disorders;effective therapy;efficacy evaluation;Elements;Eligibility Determination;emotion dysregulation;Emotions;Feedback;follow up assessment;follow-up;Frequencies;Guidelines;Health Services Accessibility;improved;indexing;Individual;innovation;Intervention;Interview;Length;Logistics;Maintenance;Measures;Meditation;Mental Depression;Mentorship;mindfulness;mindfulness meditation;Mindfulness Training;Monitor;National Center for Complementary and Integrative Health;novel;Obesity;Outcome;Overweight;Participant;Pathway interactions;Phase;Population;primary outcome;Protocols documentation;prototype;psychosocial;Public Health;Qualitative Methods;Quality of life;Randomized;Randomized, Controlled Trials;recruit;relapse patients;Research;Research Project Grants;Role;Shapes;skills;smartphone application;Source;Specialist;Symptoms;System;Technology;Testing;theories;therapy development;Training;trait;Transportation;usability;user centered design;virtual;Wait Time;web app;Weight

PROJECT_TITLE: Digital Mindfulness Meditation-enhanced Cognitive Behavioral Therapy (CBT-MM) for Binge Eating Disorder


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Health Services;Pediatric;Prevention

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Infants with brief resolved unexplained events (BRUE) and oropharyngeal dysphagia are a significant driver of pediatric health care expenditure since the mechanism for their swallow dysfunction is incompletely understood and therefore frequently goes unrecognized and untreated. We hypothesize that infants with BRUE have measurable differences in swallowing physiology to explain their symptoms of cyanotic choking spells, that these differences can be quantified using pharyngeal high resolution impedance-manometry compared to videofluoroscopic swallow study results, that this swallowing dysfunction can be safely corrected with a change of formula viscosity, and that patients receiving thickening will have improved clinical outcomes compared to patients who do not receive thickening. Through this career development award, we will systematically investigate the effects of thickened feedings on swallow function and clinical outcomes in infants with BRUE, perform detailed physiology studies on pharyngeal and esophageal motility as critical mediators of improved outcomes, and complete a decision analysis to identify the subgroup of infants with BRUE that can safely receive empiric thickening of feeds as treatment for their oropharyngeal dysphagia.

PI_NAMEs: DUNCAN, DANIEL R. (contact)

PROGRAM_OFFICER_NAME: LOH, KATRINA SHUEH WEN

PROJECT_TERMS: Academy;Address;Advisory Committees;Algorithms;American;Appearance;aspirate;Belief;Boston;brief intervention;burden of illness;career;Caring;Child;Child health care;Childhood;Choking;Clinical;clinical care;Clinical Research;Clinical Trials Design;cohort;common symptom;cost;Coughing;course development;Cross-Over Studies;Cross-Sectional Studies;Cyanosis;Data;Decision Analysis;Deglutition;Derivation procedure;Development;Disease;electric impedance;Emergency department visit;Environment;Esophagus motility;Etiology;Evaluation;Event;evidence base;Evidence based treatment;experience;feeding;Feeds;Frequencies;Frustration;Functional disorder;Goals;Guidelines;health care service utilization;Health Expenditures;high risk;Hospitalization;improved;improved outcome;indexing;Infant;innovation;Instruction;instructor;Intervention;Investigation;K-Series Research Career Programs;Knowledge;Life;Liquid substance;Longitudinal cohort study;Manometry;Measurable;Measures;Mechanics;Mediator;Medical;medical schools;Mentors;Mentorship;Modeling;modifiable risk;Morbidity - disease rate;Neonatal;Oropharyngeal Dysphagia;Outcome;Pallor;Parents;patient oriented research;Patient Outcomes Assessments;Patients;Pediatric Hospitals;pediatrician;Pediatrics;persistent symptom;personalized medicine;Pharyngeal structure;Physiological;Physiology;Pilot Projects;Population;predicting response;programs;prospective;Prospective cohort;Prospective Studies;Public Health Schools;Quality of life;randomized trial;Recommendation;Recording of previous events;Recurrence;reduce symptoms;Research;Research Activity;Research Personnel;Resolution;Resources;Risk;Risk Factors;Safety;Scholarship;skills;spelling;Subgroup;Symptoms;Techniques;Testing;Thick;Thinness;Training;Training Activity;treatment strategy;United States;Viscosity

PROJECT_TITLE: Effect of Thickened Feeds on Swallow Physiology and Clinical Outcomes in Children with Brief Resolved Unexplained Event

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Eye Disease and Disorders of Vision;Genetics;Lung;Lung Cancer;Rare Diseases

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE Acquired resistance to targeted therapy poses a major barrier to curing cancer, but the molecular mechanisms that allow cancer cells to adapt to therapy remain poorly understood. I propose to elucidate mechanisms of resistance to multiple therapies in use or in trial to treat non-small cell lung cancer (NSCLC) by identifying novel regulators of the cell cycle and lung cancer cell identity. This work will provide novel insight into the principles that govern cancer cell plasticity and may help identify ways to improve the efficacy of targeted therapies in NSCLC and other cancers.

PI_NAMEs: CHAIKOVSKY, ANDREA CHRISTINE (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Adenocarcinoma Cell;Bar Codes;Biochemical;Bioinformatics;Biological Assay;cancer cell;Cancer cell line;Cancer Etiology;cancer subtypes;cancer type;career;CDK4 gene;Cell Cycle;Cell Cycle Progression;Cell Line;Cells;Cessation of life;Characteristics;Clinic;Complex;CRISPR screen;CRISPR/Cas technology;Cyclin D1;Cyclin-Dependent Kinase Inhibitor;Cyclins;Diagnosis;Disease;Disease Progression;driver mutation;Drug resistance;experimental study;follow-up;G1/S Transition;Gene Targeting;Genes;Genetic study;Genetically Engineered Mouse;genome-wide;Global Change;Goals;improved;In Vitro;in vivo;in vivo Model;inhibitor;insight;Ligase;Lung Adenocarcinoma;lung cancer cell;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Molecular;mouse model;mutant;neuroendocrine cancer;Neurosecretory Systems;Non-Small-Cell Lung Carcinoma;novel;Oncogenic;Pathway interactions;Patient-Focused Outcomes;Patients;Phase;Phosphorylation;Phosphotransferases;Postdoctoral Fellow;prevent;Process;Proteins;receptor;Receptor Protein-Tyrosine Kinases;Relapse;Research;Research Personnel;Research Project Grants;Resistance;resistance mechanism;response;restraint;Retinoblastoma;retinoblastoma pathway;retinoblastoma tumor suppressor;Role;Route;Signal Pathway;small cell lung carcinoma;small molecule;small molecule inhibitor;Stress;Structure;success;targeted treatment;Testing;therapy resistant;Time;transdifferentiation;tumor;tumor progression;Tumor Suppressor Proteins;tumorigenesis;Tyrosine Kinase Inhibitor;ubiquitin-protein ligase;Ubiquitination;Work

PROJECT_TITLE: Investigating the Role of Cell Plasticity in Malignant Transformation


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Gene Therapy;Genetics;Organ Transplantation;Rare Diseases;Regenerative Medicine;Transplantation

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Health Relevance In this work we propose to develop a novel smart graft engineering platform, which can sensitively measure local tissue signaling would enable practical monitoring and diagnosis of acute rejection episodes, can transform care of transplant patients since compliance issues in medication would be dramatically reduced, and will likely increase the overall efficacy and therefore reduce graft rejections. In the longer term, the preservation methods developed here could also be enabling for tolerance induction in VCA transplants, and therefore allow for their wide-spread use which is not possible currently.

PI_NAMEs: CETRULO, CURTIS LISANTE;PAREKKADAN, BIJU ;UYGUN, KORKUT  (contact)

PROGRAM_OFFICER_NAME: FEHR, TUBA HALISE

PROJECT_TERMS: Acute;Allogenic;allograft rejection;Allografting;Animals;Anti-Inflammatory Agents;Attenuated;Automobile Driving;Biological Markers;Biosensing Techniques;Biosensor;Blood;Blood Vessels;blood-based biomarker;Bone Marrow;Burn injury;Calculi;candidate selection;Caring;CD34 gene;Cell Density;Cell Transplantation;cell type;Cells;Characteristics;Chimerism;Clinical;clinically relevant;CMV promoter;Complex;cost;Coupled;Defect;Development;Diagnosis;dosage;Dose;efficacy testing;Engineering;Engraftment;Ensure;Ethics;experimental study;facial transplantation;Generations;Genes;Genetic;Genetic Engineering;genetically modified cells;Goals;Graft Rejection;Hand;Health;immunogenicity;immunoreaction;immunoregulation;immunosuppressed;Immunosuppression;improved;In Vitro;in vivo;in vivo engraftment;in vivo evaluation;Inbreeding;Interleukins;Intervention;Isolated limb perfusion;Libraries;limb transplantation;Long-Term Effects;Luciferases;Macrophage;manufacture;Measures;Methods;Modeling;Modification;Monitor;NF-kappa B;novel;Organ Transplantation;Patients;Performance;Perfusion;Pharmaceutical Preparations;Plasma;preservation;pressure;promoter;prospective;Proteins;Protocols documentation;Quality Control;Quality of life;Rattus;reconstruction;Recovery;release factor;Reporter;response;response biomarker;Response Elements;Rodent Model;Sampling;sensor;Serum;side effect;Signal Transduction;Site;Solid;synthetic biology;System;Technology;Temperature;Testing;theranostics;Therapeutic;therapeutic protein;Time;Tissues;transcription factor;Transcriptional Regulation;Transplant Recipients;Transplantation;Transportation;Trauma;Upper Extremity;Vascular Graft;Vascularized Composite Allotransplantation;Work

PROJECT_TITLE: Genetic-engineered control of the immunogeneic state of vascular composite allografts during preservation

STUDY_SECTION: BTSS

STUDY_SECTION_NAME: Bioengineering, Technology and Surgical Sciences Study Section[BTSS]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Data Science;Lung;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: NARRATIVE We propose to develop a novel multiscale machine-learning microscopy platform for automated, large-scale analyses of single cells. By integrating new computational optics with deep learning, this new system will enable high resolution (0.4 μm) and large field-of-view (10 mm2) volumetric imaging and automatically identify hidden phenotypes from millions of single cells. We will apply the developed technology to map out the live cell phenotypes in iPSC(induced Pluripotent Stem Cell)-derived airway epithelium.

PI_NAMEs: LEE, HAKHO ;LEE, KWONMOO  (contact)

PROGRAM_OFFICER_NAME: SHENOY, SIDDHARTH KAUP

PROJECT_TERMS: 3-Dimensional;Adopted;airway epithelium;Algorithms;analytical tool;Biological Process;Cell Differentiation process;Cell Physiology;cell type;Cells;Cellular biology;cellular imaging;Cellular Structures;Code;Color;Complex;cost;Cystic Fibrosis;Cystic Fibrosis Transmembrane Conductance Regulator;Data;Data Analyses;Data Set;deep learning;design;Detection;Development;Diagnosis;digital imaging;Disease;disease model;disease phenotype;Epithelium;feature selection;Goals;Heterogeneity;high resolution imaging;Homeostasis;Human;human induced pluripotent stem cells;Image;Image Analysis;imaging platform;imaging system;in vitro Model;Individual;induced pluripotent stem cell;innovation;insight;Knowledge;large datasets;Learning;Light;Lighting;live cell imaging;live cell microscopy;Lung;Machine Learning;Maps;Methods;Microfluidic Microchips;Microscope;Microscopy;Modeling;Molecular;Monitor;Morbidity - disease rate;mortality;movie;Mucociliary Clearance;multidimensional data;novel;operation;Optics;Phenotype;Play;Population;Positioning Attribute;Process;Protocols documentation;reconstruction;Research;Resolution;respiratory;Respiratory Disease;Role;Scanning;Series;single cell analysis;single-cell RNA sequencing;Source;spatiotemporal;Structure;supervised learning;Supervision;System;Techniques;Technology;temporal measurement;Testing;therapeutically effective;three dimensional cell culture;Time;Tissues;tomography;tool;trait;Transcend

PROJECT_TITLE: High-throughput Phenotyping of iPSC-derived Airway Epithelium by Multiscale Machine Learning Microscopy

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


NIH_SPENDING_CATS: Arthritis;Autoimmune Disease;Clinical Research;Microbiome;Rheumatoid Arthritis

ORG_CITY: SAN FRANCISCO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Rheumatoid arthritis (RA) is a debilitating autoimmune disease affecting over one million Americans, and while first-line therapy with methotrexate (MTX) works for many, in most patients, it is not enough. Our recent studies indicate that the gut microbiome plays important roles in RA treatment and that MTX acts on the microbiota to reduce inflammation. Understanding how MTX acts on the microbes to affect key metabolites may enable the development of new microbially targeted therapies to improve treatment response to MTX.

PI_NAMEs: NAYAK, RENUKA RAJENDRA (contact)

PROGRAM_OFFICER_NAME: MAO, SU-YAU

PROJECT_TERMS: Adenosine;Affect;American;Anti-Inflammatory Agents;Antiinflammatory Effect;Arthritis;Autoimmune Diseases;Bacterial Model;Bacteroides thetaiotaomicron;Bacteroidetes;Blood;clinical practice;cohort;cost effective;design;Development;Dose;Enzymes;extracellular;Feces;Folic Acid;Foundations;Future;Genetic Models;Gnotobiotic;Goals;Grant;Growth;gut bacteria;gut microbiome;gut microbiota;Human;immune activation;Immunity;improved;In Vitro;in vivo;Individual;Inflammation;Inflammatory Arthritis;innovation;Knowledge;Link;Measures;Mediating;Metabolic;Metabolism;metabolome;metabolomics;Methotrexate;Microbe;microbial;microbiota;Molecular;Mus;mutant;Pathway interactions;patient response;Patients;Pharmaceutical Preparations;Play;Pre-Clinical Model;precision medicine;responders and non-responders;response;Rheumatism;Rheumatoid Arthritis;Rheumatology;Role;Shapes;skin disorder;T-Lymphocyte;targeted treatment;Testing;Transplantation;treatment response;Work

PROJECT_TITLE: Microbial metabolites impacting the response to methotrexate in rheumatoid arthritis

STUDY_SECTION: AMS

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Special Grants Study Section[AMS]


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Pediatric;Rare Diseases

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: Project Narrative Proper heart development is critical, as congenital heart defects are the most common malformations and frequent cause of death in newborns. The information gleaned from this project will provide a better understanding of normal heart development and congenital heart defects, which may allow us to generate of novel therapies able to prevent or ameliorate congenital heart defects and arrythmias in children and adults.

PI_NAMEs: WAXMAN, JOSHUA  (contact)

PROGRAM_OFFICER_NAME: SCHRAMM, CHARLENE A

PROJECT_TERMS: Adopted;Adult;Alleles;apoAI regulatory protein-1;Arrhythmia;Atrial Heart Septal Defects;Binding Sites;Biological Assay;Cardiac;Cardiac Myocytes;cardiogenesis;Cause of Death;chicken ovalbumin upstream promoter-transcription factor;Child;Chromatin;Complication;Congenital Abnormality;Congenital Heart Defects;Data;Defect;Development;Differentiated Gene;Electrophysiology (science);Embryo;EMSA;Enhancers;Epigenetic Process;Etiology;Failure;Foundations;FOXF1 gene;Frequencies;Gene Expression;Gene Expression Profiling;gene regulatory network;Genes;Genetic;Genetic Epistasis;genome editing;Genomics;Glean;Goals;Heart;Heart Atrium;Human;in vivo;loss of function;Luciferases;Maintenance;malformation;Molecular;Morbidity - disease rate;mortality;Mus;mutant;Mutation;Neonatal Mortality;Newborn Infant;novel;novel strategies;novel therapeutics;Nuclear Hormone Receptors;Operative Surgical Procedures;Organ;Organogenesis;Orphan;overexpression;Pacemakers;Patients;pharmacologic;Prevalence;prevent;Reagent;Regulation;Regulatory Element;Repression;Signal Transduction;single-cell RNA sequencing;Sinoatrial Node;Sorting;Structural defect;Techniques;Testing;Tissues;transcription factor;transcriptomics;transdifferentiation;Transgenic Organisms;Venous;Ventricular;Vertebrates;WNT Signaling Pathway;Work;Zebrafish

PROJECT_TITLE: Mechanisms governing the differentiation and maintenance of atrial identity

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


NIH_SPENDING_CATS: Contraception/Reproduction;Estrogen;Genetics;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: DALLAS

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Narrative The cervical epithelium serves as the first line of defense during pregnancy to prevent ascending infections, a risk factor for preterm birth. Using single cell approaches, diverse subtypes of epithelial cells were identified in pregnancy that were unique in gene expression compared to nonpregnant. In the current study, the lineage and regulation of specialized secretory epithelia that are dominant in pregnancy will be identified and the impact on ascending infection risk determined when the secretory cells are perturbed. Insights from this work will identify biomarkers that predict risk of preterm birth and identify therapeutic clinical targets for prevention.

PI_NAMEs: MAHENDROO, MALA S. (contact)

PROGRAM_OFFICER_NAME: ILEKIS, JOHN V

PROJECT_TERMS: Automobile Driving;Basal Cell;Biological Markers;biomarker identification;Cell Differentiation process;Cell Physiology;Cell Proliferation;cell type;Cells;Cervical;cervical remodeling;cervicovaginal;Cervix Uteri;Clinical;Columnar Epithelium;Computer Analysis;Data;Data Set;Defect;Disease;Ensure;Epithelial Cells;Epithelium;Estrogens;experimental study;Exposure to;Eye;Fertility;Functional disorder;Gastrointestinal tract structure;Gel;Gene Expression;gene regulatory network;Genetic Transcription;Goals;Goblet Cells;Health;Homeostasis;Hormones;immune function;Immunologic Surveillance;improved;In Vitro;in vivo;Infection;infection risk;Inflammation;Inflammation Mediators;Inflammatory Response;insight;Knowledge;Late pregnancy;Lipopolysaccharides;Liquid substance;Lung;Measures;Mediating;Microbe;Modeling;Molecular;Monitor;Mucous body substance;Mucous Membrane;Mus;Natural Immunity;OLFM4 gene;Organoids;Outcome;Ovariectomy;pathogen;Phase;Phenotype;Pilot Projects;Play;Population;Pregnancy;Pregnancy Maintenance;Premature Birth;prevent;Prevention;Process;Production;Progesterone;programs;Proliferating;Prostate;Regulation;response;Risk;Risk Factors;risk prediction;Role;Secretory Cell;Signal Transduction;single cell analysis;single-cell RNA sequencing;Sorting;Specificity;Squamous Epithelium;stem cell biomarkers;stem cell population;stem cells;steroid hormone;Steroids;System;Testing;Therapeutic;Time;transcription factor;transcriptomics;transdifferentiation;vaginal fluid;Woman;Work

PROJECT_TITLE: Functional and Molecular Characterization of Epithelial Subtypes in Cervical Remodeling and Preterm Birth

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-EMS-L(02)M]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Chronic Pain;Epilepsy;Neurodegenerative;Neurosciences;Pain Research

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: PROJECT NARRATIVE  The vast majority of diseases that severely afflict the public health are consequence of derangements in the molecular mechanisms by which our cells respond to external stimuli. Here we propose studies to identify a new molecular mechanism that regulates signaling via G protein coupled receptors (GPCRs), which are prominent pharmacological targets for a wide range of diseases. The most direct, but not exclusive, implications of these studies are in the area of epilepsy and pain.

PI_NAMEs: GARCIA-MARCOS, MIKEL  (contact)

PROGRAM_OFFICER_NAME: MATOS GALICIA, HEIDI YANICE

PROJECT_TERMS: Achievement;Adenylate Cyclase;Affect;Area;Binding;Binding Proteins;Biological Assay;Biosensor;Brain;Brain region;Cell Physiology;Cells;Chronic inflammatory pain;chronic pain;Coin;Communication;Complex;Coupled;Cyclic AMP;Cytoplasm;Cytoplasmic Protein;Data;Disease;Ensure;Epilepsy;Excitatory Synapse;Family;G Protein-Coupled Receptor Signaling;G-Protein Signaling Pathway;G-Protein-Coupled Receptors;Gene Modified;Genetic;Goals;Grant;GTP-Binding Protein Regulators;GTP-Binding Proteins;GTPase-Activating Proteins;Guanine Nucleotide Dissociation Inhibitors;Guanosine Triphosphate;Heterotrimeric GTP-Binding Proteins;human disease;Hydrolysis;Hyperalgesia;Impact Seizures;Impairment;In Vitro;Inhibitory Synapse;insight;Ion Channel;Knockout Mice;Laboratories;Link;Maps;Mass Spectrum Analysis;Mechanics;Mediating;Mediator;member;Molecular;mouse model;Nervous System Disorder;Neurons;neuroregulation;neurotransmission;Neurotransmitters;novel;Nucleotides;Pain;painful neuropathy;Pattern;Peripheral Nervous System;pharmacologic;Physiological;Physiology;Population;Post-Translational Protein Processing;postsynaptic;Predisposition;Process;protein purification;Proteins;prototype;Public Health;receptor;Regulation;Reporting;response;RGS Proteins;Role;Seizures;Signal Transduction;Signaling Protein;Site;Slice;Specificity;Spinal Ganglia;Stimulus;Synapses;Testing;Therapeutic

PROJECT_TITLE: Alternative Mechanisms of Signaling Via Trimeric G Proteins

STUDY_SECTION: MNPS

STUDY_SECTION_NAME: Molecular Neuropharmacology and Signaling Study Section[MNPS]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: IOWA CITY

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative The protein kinase PKA protects against dementia in Alzheimer’s disease and during aging, and drugs that activate PKA are in clinical development for the treatment of dementia. This proposal investigates the ability of PKA to form liquid-like droplets in cells in order to gain a better understanding of PKA’s protective function in the brain.

PI_NAMEs: STRACK, STEFAN  (contact);TAYLOR, SUSAN S.

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: Acceleration;Adult;Age;Age Months;age related;Aging;Alleles;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease related dementia;amyloid formation;Antibodies;Binding;Biochemical;Biochemistry;Biological Assay;biophysical techniques;Biosensor;Brain;Buffers;cell type;Cells;Child;clinical development;Cognitive;Collaborations;CREB1 gene;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Data;Dementia;Development;Disease;Epitopes;Fluorescence Recovery After Photobleaching;Frontotemporal Dementia;Genes;Genetic Transcription;Heterozygote;Human;Image;imaging approach;Immunofluorescence Immunologic;Impaired cognition;improved;in vivo;Institution;Intellectual functioning disability;Label;Learning;Link;Liquid substance;live cell imaging;Mediating;Memory;Memory impairment;Memory Loss;Microtubules;Modeling;Molecular;mosaic;Motor;motor learning;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;Neuroglia;Neurologic Symptoms;Neurons;new therapeutic target;novel;Pathogenicity;Pathology;Pharmaceutical Preparations;Phase;Phosphodiesterase Inhibitors;Physical condensation;prevent;Property;protein degradation;Protein Kinase;Protein Subunits;Proteins;Reporting;Resolution;Role;Signal Pathway;Signal Transduction;spatial memory;Specificity;Synaptic plasticity;tau aggregation;tau Proteins;tau-1;tau-protein kinase;Tauopathies;Testing;Therapeutic;therapy development;tool;Treatment Efficacy

PROJECT_TITLE: Interplay between tau and PKA condensates in ADRD


NIH_SPENDING_CATS: Biotechnology;Cancer;Colorectal Cancer;Digestive Diseases;Genetics;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: FARMINGTON

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: Relevance Lynch syndrome (LS) is a hereditary disease which predisposes patients to an increased risk of developing colorectal, endometrial, ovarian and other cancers. Diagnosis of LS is aided by identification of a deleterious, germline mutation in one of four DNA mismatch repair (MMR) genes, however, nearly one-fourth of all suspected patients carry germline missense variants in the MMR genes which alter only a single amino acid in these rather large proteins. This proposal seeks to utilize a human stem cell culture model system for testing whether certain missense variants affect MMR cellular functions; an important step in determining whether the variant truly contributes to disease pathogenesis.

PI_NAMEs: HEINEN, CHRISTOPHER D. (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: Affect;Amino Acids;Apoptotic;Biochemical;Biological Assay;Biological Models;Cancer cell line;Cancer Etiology;Cancer Patient;Cell Culture Techniques;Cell Differentiation process;cell immortalization;cell injury;Cell Physiology;Cell Survival;cell type;Cells;Cessation of life;Classification;Classification Scheme;Colon;colon cancer patients;Colon Carcinoma;Colorectal;Colorectal Cancer;CRISPR/Cas technology;Defect;Detection;Development;Diagnosis;Disease;DNA;DNA Damage;DNA sequencing;Endometrial;Engineering;Environment;Event;Failure;Family;Family member;Frustration;Gene Expression;gene function;gene repair;Gene Targeting;Genes;Genetic;genetic counselor;genetic variant;Genome Stability;Genomic Instability;genomic locus;Germ Lines;Germ-Line Mutation;Goals;Guidelines;Hereditary Disease;Hereditary Malignant Neoplasm;Hereditary Nonpolyposis Colorectal Neoplasms;Human;human pluripotent stem cell;human stem cells;In Vitro;Individual;Induction of Apoptosis;Inherited;Intestines;Label;Laboratories;Laboratory Study;Malignant Neoplasms;Masks;Measures;Mediating;men;Microsatellite Instability;Mismatch Repair;Missense Mutation;MLH1 gene;Modeling;MSH2 gene;MSH6 gene;Mutation;Nature;Organoids;Ovarian;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Phenotype;Physicians;Pluripotent Stem Cells;Population;prevent;protein expression;protein function;Proteins;repair function;repaired;response;Risk;senescence;stem cells;Testing;Time;Transgenes;Uncertainty;Variant;variant of unknown significance;Woman

PROJECT_TITLE: Hereditary Cancer Variants of Uncertain Significance in Stem Cells

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Infectious Diseases;Lung;Patient Safety;Pediatric;Prevention

ORG_CITY: BALTIMORE

ORG_DEPT: PEDIATRICS

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE: Little is known regarding why children with tracheostomy experience recurrent respiratory infections despite receiving clinically appropriate antibiotic therapy. This proposal seeks to derive a novel prognostic model that incorporates clinical factors and mechanistically-based laboratory measures of pathogen antibiotic resistance and host immune response to identify children at greatest risk for recurrent tracheostomy-associated respiratory infections (TARIs). The findings of this work under a career development award will provide the basis for future risk-stratified interventional trials employing targeted therapies to reduce the frequency of TARI hospitalization among children with tracheostomy.

PI_NAMEs: MORRISON, JOHN M (contact)

PROGRAM_OFFICER_NAME: REYES, MADELYN

PROJECT_TERMS: Acute;Acute respiratory infection;Admission activity;Affect;Antibiotic Resistance;Antibiotic Therapy;antibiotic tolerance;Antibiotics;Area;aspirate;Basic Science;biobank;Biological Markers;biomarker discovery;biomarker validation;Biometry;care providers;career;career development;Career Mobility;Caring;Characteristics;Child;Child Care;Childhood;Chronic;Clinical;clinical prognostic;Clinical Research;clinical risk;Clinical Sciences;Clinical Trials;cohort;Complement;Complex;Conduct Clinical Trials;cost;Data;Dedications;Dependence;design;Development;Education;efflux pump;Enrollment;Exhibits;experience;Foundations;Frequencies;Funding;Future;Goals;hospital readmission;Hospitalization;hospitalization rates;Hospitalized Child;Human;Immune response;improved;improved outcome;Incidence;Individual;Infection;infection risk;inflammatory marker;Inflammatory Response;Institution;Interleukin-10;Interleukin-6;Intervention Studies;Intervention Trial;K-Series Research Career Programs;Knowledge;Knowledge acquisition;Laboratories;Length of Stay;Measures;Mechanical ventilation;Medical;medical schools;Mentors;Mentorship;Modeling;Molecular;Molecular Epidemiology;Morbidity - disease rate;Multicenter Studies;Neuromuscular Diseases;novel;novel marker;Outcome;pathogen;Patients;Pediatric Hospitals;Pediatrics;Physicians;Plasma;Play;Predisposition;professor;Prognostic Factor;prognostic model;prospective;Prospective cohort;Prospective, cohort study;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Public Health Schools;quorum sensing;Recurrence;recurrent infection;Research;Research Personnel;Resources;respiratory;Respiratory Failure;Respiratory Tract Infections;Risk;Risk Factors;risk stratification;ROC Curve;Role;Scientist;secondary analysis;Serum;skill acquisition;Specimen;System;targeted treatment;Therapeutic;Trachea;Tracheostomy procedure;Tracheotomy procedure;Training;Translational Research;trial design;Universities;validation studies;Work

PROJECT_TITLE: Prognostic modeling of pediatric tracheostomy-associated respiratory tract infections

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(JA)]


NIH_SPENDING_CATS: Biotechnology;Genetics;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Narrative At the cellular level, mesenchymal stem cells experience physical force (“exercise”) transferred through the actin cytoskeleton and into the nucleus, activating signaling and changing nuclear structure. Recently it has become apparent that nuclear structure itself has a profound effect on gene expression, and alterations in the nucleoskeleton can prevent stem cells from becoming osteoblasts. We propose to find out how different types of force, through their respective induced cytoskeletons, affect nuclear structure and the expression of osteogenic genes.

PI_NAMEs: RUBIN, JANET E (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: Actins;Address;Affect;Architecture;beta catenin;Biomechanics;bone;Bone Marrow;bone marrow mesenchymal stem cell;Cell Lineage;Cell Nucleus;Cells;Chromatin;Cytoplasm;Cytoskeleton;Data;DNA;DNA Repair;Epigenetic Process;epigenetic regulation;Euchromatin;Exercise;experience;EZH2 gene;F-Actin;Focal Adhesions;Gene Activation;Gene Expression;Gene Silencing;Gene Targeting;Genes;Genome;Heterochromatin;histone methylation;inhibitor;knock-down;Lamin B1;Lamins;Link;lipid biosynthesis;loss of function;Marrow;Measures;mechanical force;mechanical stimulus;Mechanics;Mediating;Mesenchymal;Mesenchymal Stem Cells;Modeling;Nature;novel;Nuclear;Nuclear Envelope;Nuclear Import;Nuclear Pore;Nuclear Structure;nuclear transfer;Nuclear Translocation;Osteoblasts;Osteogenesis;osteogenic;Physical condensation;polymerization;Polymers;Positioning Attribute;PPAR gamma;prevent;programs;Proliferating;promoter;Publishing;Regulatory Pathway;response;Role;Signal Induction;Signal Pathway;Signal Transduction;Small Interfering RNA;stem;stem cell differentiation;stem cell fate;stem cells;stemness;Stimulus;Stress;Stromal Cells;Structure;Testing;transcription factor;transcriptome;transcriptome sequencing;Variant

PROJECT_TITLE: Role of force regulated nuclear structure in expression of osteogenesis


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Emergency Care;Neurosciences

ORG_CITY: OMAHA

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Project Narrative Tourniquet-induced traumatic injuries limit its clinical use for effectively stopping life-threatening bleeding in prehospital settings and creating bloodless operating fields in surgeries. This proposal will explore the potential mechanisms about tourniquet-induced traumatic injuries and test whether a new anti-inflammatory drug promotes long-term recovery of the neuromuscular junction from traumatic injuries. The significance of this project is to resolve the limitations of tourniquet use in the clinic and to provide potential therapeutic targets and strategies for improving outcomes and quality of life in post-traumatic patients.

PI_NAMEs: LI, YU-LONG  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Accident and Emergency department;Acute;Address;Affect;Age;Animals;Anti-Inflammatory Agents;beta catenin;Binding;Blood Vessels;Cell Line;Cessation of life;Chronic;Clinic;Clinical;cost;Cyclin-Dependent Kinase 5;cytokine;Cytokine Receptors;Data;design;Dexamethasone;Drug Delivery Systems;effective therapy;Embryo;emergency service responder;Emergency Situation;Functional disorder;Hemorrhage;Hindlimb;improved;improved outcome;In Vitro;in vivo;Inflammation;Inflammatory;injured;Interleukin 6 Receptor;Interleukin-1 beta;Interleukin-6;Ischemia;Life;limb injury;Limb structure;Link;long term recovery;Measurable;Mediating;Medicine;Membrane;Modeling;Molecular;Motor;mouse model;Mus;Muscle;Muscle Contraction;Muscle function;muscular structure;Nerve;Neuromuscular Junction;Neuromuscular Junction Diseases;Nicotinic Receptors;novel;novel therapeutics;Operative Surgical Procedures;Orthopedics;Outcome;overexpression;Patients;peripheral membrane protein 43K;Pharmaceutical Preparations;Polyethylene Glycols;Pre-hospital setting;Prodrugs;Production;Prognosis;Protein Array;Quality of life;receptor;Recovery;reinnervation;repaired;Reperfusion Injury;Reperfusion Therapy;Route;sciatic nerve;side effect;Signal Pathway;Signal Transduction;Site;Skeletal Muscle;Structure;Synapses;Testing;Therapeutic;Therapeutic Effect;therapeutic target;Tissues;TNF gene;tool;Tourniquets;transcriptome sequencing;transmission process;Trauma;Traumatic injury;Treatment Efficacy;Visit

PROJECT_TITLE: Neuromuscular junction as a therapeutic target to improve post-traumatic outcomes

STUDY_SECTION: SAT

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


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Emerging Infectious Diseases;Genetics;Human Genome;Infectious Diseases;Pediatric;Primary Immunodeficiencies;Rare Diseases;Tuberculosis

ORG_DEPT: GENETICS

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: Project Narrative The 31 known inborn errors of IFN-γ-mediated immunity underlying MSMD are found in about half of the 900 international patients with MSMD enrolled in the laboratory. We will search for novel MSMD-candidate genotypes in the remaining patients by WES or WGS, testing hypotheses of genetic homogeneity or heterogeneity. We will establish causality between these candidate genotypes and MSMD by in-depth mechanistic studies at the molecular, cellular, and immunological levels.

PI_NAMEs: BUSTAMANTE, JACINTA ;CASANOVA, JEAN-LAURENT  (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: Affect;Alleles;Architecture;autosome;Awareness;BCG Vaccine;Candidate Disease Gene;candidate selection;Candidiasis;Child;Clinical;cohort;Communicable Diseases;computerized tools;congenital immunodeficiency;Data;Defect;Development;Disease;disease-causing mutation;Dissection;Dominant Genetic Conditions;Dryness;Enrollment;Etiology;exome sequencing;Exons;Experimental Genetics;Family;Genes;Genetic;Genetic Counseling;Genetic Diseases;Genetic Heterogeneity;Genetic Models;Genetic Predisposition to Disease;Genetic study;genome sequencing;genome-wide;Genotype;Genus Mycobacterium;Hematopoietic Stem Cell Transplantation;Hereditary Disease;Heterogeneity;Human;Human Genetics;IFNGR1 gene;IFNGR2 gene;IL12B gene;IL12RB1 gene;IL12RB2 gene;Immunity;Immunologics;Impairment;Individual;innovation;insight;Interferon Type II;International;Introns;Investigation;IRF1 gene;ISG15 gene;JAK1 gene;kindred;Laboratories;Leadership;Lesion;Life;Link;Mediating;Medical;Mendelian susceptibility to mycobacterial disease;microorganism;Molecular;Molecular Diagnosis;Molecular Genetics;Mutate;Mutation;mycobacterial;novel;Parents;pathogen;Pathogenesis;Pathway interactions;Patient Recruitments;Patients;Penetrance;Phenotype;Physicians;Physiological;Predisposition;Preventive;Primary Infection;Probability;protein expression;Publications;recessive genetic trait;Recombinants;recurrent infection;Research;Research Project Grants;response;Role;Salmonella;Siblings;STAT1 gene;Structure;Technology;Testing;Therapeutic;Therapeutic Uses;trait;Tuberculosis;TYK2;Type I Interferonopathy;United States National Institutes of Health;Validation;Variant;Virulent;Virus Diseases;whole genome;Work

PROJECT_TITLE: Genome-Wide Dissection of Mendelian Susceptibility to Mycobacterial Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-N(90)S]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Estrogen;Neurosciences;Sleep Research;Women's Health Research

ORG_CITY: MILWAUKEE

ORG_NAME: MARQUETTE UNIVERSITY

ORG_STATE: WI

PHR: PROJECT NARRATIVE Seasonal changes in day length cause physiological and psychiatric disturbances that relapse every year. There is a large gender disparity in seasonal disorders, with women at least twice as likely as men to be adversely affected. Understanding the basis of seasonal disease and why women are affected so disproportionately is an area of critical unmet need. These studies will generate novel insights into how day length alters the function of neural circuits in both sexes, which will comprise the basic foundations for identifying novel ways to combat seasonal pathology.

PI_NAMEs: EVANS, JENNIFER ANNE (contact);SAVTCHOUK, IAROSLAV ;SCHMIDT, TIFFANY M.

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: Acceleration;Acute;Affect;American;Area;Arrhythmia;Attention;Automobile Driving;Behavior;behavioral response;biological sex;Biological Testing;Brain;cell type;Cells;cellular imaging;Chlorides;circadian;combat;Computer Analysis;Data;day length;Desire for food;Disease;Down-Regulation;Exclusion;Female;Foundations;gamma-Aminobutyric Acid;gender disparity;Health;immune function;insight;Jet Lag Syndrome;Justice;Light;Link;male;Mediating;men;Metabolism;molecular clock;Moods;Mus;Nervous System Physiology;neural circuit;neuroadaptation;neurobiological mechanism;neuromechanism;Neurophysiology - biologic function;novel;optogenetics;Pathology;Pathway interactions;Personal Satisfaction;Persons;Photoperiod;photoperiodicity;Physiological;Physiology;Process;Property;Recovery;Relapse;Reporter;Research;response;Retina;Retinal Ganglion Cells;Risk;Seasons;segregation;sex;Sex Differences;sexual dimorphism;shift work;Signal Transduction;Sleep;Stimulus;Structure;suprachiasmatic nucleus;symporter;Test Result;Testing;Time;Woman;Work

PROJECT_TITLE: Sexual dimorphic circuits in photoperiodic encoding and photic processing

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Bioengineering

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Molecular-scale interactions govern cell biology, and super-resolution microscopy has emerged as a powerful tool for attaining nanoscopic maps of the inside of the cell. This work will develop novel super-resolution microscopy tools to characterize the biochemical reactions occurring in bacterial cells in real time. By providing synergistic information—localization maps, interaction maps, and mobility maps—we will investigate broad themes in bacterial cell biology to develop new paradigms for subcellular organization in these small cells.

PI_NAMEs: BITEEN, JULIE  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: Address;Bacteria;Bacterial Model;Bacteriology;Biochemical Reaction;Biochemistry;Biology;Biophysics;Caulobacter crescentus;cell fixing;Cell Physiology;cell type;Cells;Cellular biology;Color;commensal bacteria;Communities;Cyanobacterium;data quality;Data Set;Detection;Diffusion;Disease;DNA;Escherichia coli;Eukaryota;fighting;Fluorescence;Goals;Health;Human;human disease;Image;Imaging Device;improved;In Vitro;in vitro Model;innovation;Maps;Measurement;Measures;Methods;microbial;Modeling;Molecular;molecular scale;Motion;nano;nanoscale;next generation;novel;novel strategies;organizational structure;Outcome;Phase;Physical condensation;Positioning Attribute;Prokaryotic Cells;Proteins;Resolution;Ribonucleoproteins;Role;scaffold;single molecule;spatiotemporal;statistics;Structure;superresolution imaging;superresolution microscopy;System;Testing;Time;tool;Tube;ultra high resolution;Work

PROJECT_TITLE: Mapping the Interactions and Dynamics that Organize Bacteria Cells

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Eye Disease and Disorders of Vision;Neurosciences;Rehabilitation

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: PROJECT NARRATIVE This research will contribute fundamental knowledge regarding how the primate brain represents and processes the three-dimensional (3D) world during naturalistic, unrestrained behaviors. In the short term, it will provide a novel research platform for investigating how primates encode/update ecologically relevant 3D sensory information to thrive in an ever-changing world. In the long term, it will provide fundamental knowledge for treating neurological disorders, traumatic brain injury, and cognitive dysfunction.

PI_NAMEs: KIM, BYOUNGHOON ;ROSENBERG, ARI  (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: 3-Dimensional;3D world;Animal Model;Animals;Area;Basic Science;Behavior;Behavioral;behavioral study;Binocular Vision;Biological Models;Brain;Brain region;Callithrix;cell type;Cells;Chiroptera;Chronic;Cognitive;cognitive capacity;cognitive function;Complex;Custom;Data;data acquisition;design;Development;Disease;Electrodes;Environment;environmental change;Episodic memory;Eye;Eye Movements;face mask;Female;Future;gaze;Goals;Hand;Head;Health;Hippocampus;Histology;Home;Human;Impaired cognition;Investigation;Knowledge;Limb structure;Limbic System;Location;Macaca;Macaca mulatta;Magnetic Resonance Imaging;male;Memory;Modeling;Monkeys;monocular;Motion;Motor;motor control;multisensory;Nervous System Disorder;neural;neural circuit;neural correlate;neuromechanism;Neurons;neurophysiology;Neurosciences;nonhuman primate;novel;paragon;Penetration;Positioning Attribute;Primates;Process;Property;Reflex action;Reporting;Research;Research Personnel;restraint;Rodent;Sensory;Signal Transduction;skull implant;Source;Specific qualifier value;System;Systems Integration;Technology;Testing;Traumatic Brain Injury;Update;Upper limb movement;vestibular system;virtual reality;Visual;Visual System;visual tracking;way finding;wireless;Work

PROJECT_TITLE: Novel freely moving monkey framework for the study of naturalistic behaviors

STUDY_SECTION: BNVT

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: PROVO

ORG_DEPT: CHEMISTRY

ORG_NAME: BRIGHAM YOUNG UNIVERSITY

ORG_STATE: UT

PHR: Project Narrative Pathogenic bacteria have a devastating effect on public health, and new therapies are desperately needed to combat growing antibiotic resistance. Pathogenesis-associated bacterial secretion systems are attractive drug targets, but we lack detailed understanding of their structures and mechanisms. In the proposed project, we will apply state-of-the-art imaging techniques to provide this missing information, generating functional insights into these complex nanomachines and potential drug targets for the future.

PI_NAMEs: JENSEN, GRANT J (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: 3-Dimensional;Adhesions;Antibiotic Resistance;Archaea;Architecture;Award;Bacteria;Bdellovibrio;Bioinformatics;Caulobacter crescentus;cell envelope;Cells;Cholera Toxin;combat;comparative genomics;Competence;Complex;Cryoelectron Microscopy;cryogenics;Cytoplasmic Structures;density;Development;Disparate;DNA;Docking;Drug Design;Drug Targeting;Electron Microscopy;Electrons;Escherichia coli;Evolution;Family;First Independent Research Support and Transition Awards;Fishes;Flavobacteria;Floods;Future;Genetic Conjugation;genetic information;Gram-Negative Bacteria;Grant;Helicobacter pylori;Hemagglutinin;high resolution imaging;Homologous Gene;Horizontal Gene Transfer;Human;human pathogen;Image;imaging system;Imaging Techniques;Imaging technology;In Situ;in vivo;Individual;Infection;insight;Ions;Knock-out;Legionella pneumophila;light microscopy;Location;Mannose;Maps;Mediating;member;Membrane;Modeling;Molecular;Motility;Motor;mutant;Myxococcus xanthus;nanomachine;Neptunium;novel;novel therapeutics;operation;particle;pathogen;Pathogenesis;pathogenic bacteria;Pathogenicity;Peptide Hydrolases;Periodontal Diseases;periplasm;Pilum;Porphyromonas gingivalis;Process;Proteins;Pseudomonas aeruginosa;Public Health;reconstruction;Recording of previous events;Resolution;Role;Secretin;Serotyping;Shewanella;Signal Pathway;Structure;Surface;System;Techniques;Technology;Testing;therapeutic target;Thermococcus;Time;Toxin;Tube;Type II Secretion System Pathway;Type IV Secretion System Pathway;Vaccines;Vibrio cholerae;Virulence;Work;X-Ray Crystallography

PROJECT_TITLE: Structure and Function of Pathogenesis-Associated Bacterial Structures by Electron Cryotomography


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Effects of Household Energy Combustion;Health Effects of Indoor Air Pollution;Kidney Disease;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: Aurora

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative The proposed study is directed at increasing the fundamental understanding of the causes and prevention strategies of chronic kidney disease of unknown origin (CKDu) in Latin American women. The of and effect at study's inclusion examining occupational and non-occupational exposures to particulate matter and its constituents (i.e., silica heavy metals), mechanisms of injury, markers of cellular stress and inflammation, and renal biomarkers of among females in Guatemala and Nicaragua will factors that put individuals risk for the development of CKDu. Findings will advance our ability to identify lead to interventions designed to reduce morbidity and mortality from CKDu in vulnerable populations around the world.

PI_NAMEs: NEWMAN, LEE S (contact)

PROGRAM_OFFICER_NAME: JOUBERT, BONNIE

PROJECT_TERMS: Acute;Address;Affect;agricultural community;Agricultural Workers;Agriculture;Air Pollutants;air sampling;Airborne Particulate Matter;ambient air pollution;Arsenic;Biological Markers;Biomass;Burn injury;C-reactive protein;Cadmium;Cellular Stress;Central America;Central American;Chronic;Chronic Kidney Failure;cohort;Collaborations;Communities;cooking;Cooking Practices;Country;Creatinine;cytokine;Data;Dehydration;Development;Diabetes Mellitus;Diameter;El Salvador;Epidemic;Etiology;experience;Exposure to;Female;Female Adolescents;Field Workers;fine particles;Glomerular Filtration Rate;Goals;Guatemala;Harvest;Health;Heat Stress;Heat-Shock Proteins 70;Heavy Metals;High Risk Woman;Home;Hour;Household;Hydration status;Hypertension;Individual;Inflammation;Inhalation Exposure;Injury;Injury to Kidney;International;Intervention Trial;Kidney;Kidney Diseases;kidney dysfunction;Knowledge;Latin American;LCN2 gene;Lead;Leukocytes;Link;Longitudinal Studies;male;Measures;Metals;meter;Modification;Monitor;Morbidity - disease rate;mortality;neglect;nephrogenesis;nephrotoxicity;Nicaragua;Nicaraguan;Nickel;novel;Occupational;Outcome;Participant;Particulate Matter;Pathogenesis;Pathway interactions;Plants;pollutant;Population;post gamma-globulins;Prevalence;prevent;prevent epidemics;Prevention strategy;rat KIM-1 protein;Recurrence;Renal function;Reporting;Research;Risk;Risk Factors;Saccharum;sample collection;Seasons;Serum;Silicon Dioxide;Source;Stress;Sum;systemic inflammatory response;Techniques;therapy design;Time;UMOD gene;Vulnerable Populations;Woman;women's outcomes;Women's study;Work;working men;Working Women

PROJECT_TITLE: Air pollutants, heat exposure, and kidney health: A longitudinal study in women in Central America

STUDY_SECTION: KNOD

STUDY_SECTION_NAME: Kidney, Nutrition, Obesity and Diabetes Study Section[KNOD]


NIH_SPENDING_CATS: Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Vaccine Related

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: PROJECT NARRATIVE This research proposal seeks to define how vaccination alters the course of gammaherpesvirus infection in immunocompetent mice, using the murine gammaherpesvirus 68 model system. While there is clear evidence that the immune system can limit gammaherpesvirus-induced infection, the stage at which infection is disrupted and the cell type(s) involved in protection remain poorly defined. By analyzing viral infection and immune parameters associated with control of gammaherpesvirus infection in the context of vaccination, these studies seek to address this gap in knowledge of gammaherpesvirus infection and disease in susceptible populations.

PI_NAMEs: CLAMBEY, ERIC T;VAN DYK, LINDA F. (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;acute infection;adaptive immune response;Address;Adoptive Transfer;Affect;Anti-viral Agents;Antibodies;Attenuated;Attenuated Vaccines;B-Lymphocytes;Biological Models;Cancer Etiology;CD8-Positive T-Lymphocytes;Cell Differentiation process;cell type;Cells;cross immunity;Cues;cytokine;Data;defined contribution;Dendritic Cells;Detection;Development;Disease;DNA Tumor Viruses;Frequencies;gammaherpesvirus;high dimensionality;Human;Human Herpesvirus 4;Human Herpesvirus 8;human pathogen;Immune;Immune Evasion;Immune system;Immunity;Immunocompetent;Immunosuppression;In Vitro;in vivo;Inactivated Vaccines;Individual;infected B cell;Infection;Inflammatory;Innate Immune Response;insight;Integration Host Factors;interest;Interferon Type II;Kaposi Sarcoma;Knowledge;latency-associated nuclear antigen;latent infection;latent nuclear antigen;Lytic Phase;Macrophage;Macrophage Activation;Malignant Neoplasms;Medical;Methods;mouse model;Mus;Myelogenous;Myeloid Cells;Non-Hodgkin's Lymphoma;Oncogenic Viruses;Outcome;pathogen;Pathogenesis;Pathogenicity;Pathway interactions;Population;Predisposition;prevent;Primary Infection;Process;Regulation;Research Proposals;response;Risk;Role;single cell analysis;Stimulus;success;System;T-Lymphocyte;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;Time;Training;Tropism;Vaccination;vaccination protocol;vaccine efficacy;vaccine trial;Vaccines;Viral;Virus;Virus Diseases

PROJECT_TITLE: Therapeutic targets in gammaherpesvirus infection

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


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

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Anti-estrogen therapy is key to the prevention and treatment of estrogen receptor (ER, ESR1) positive breast cancer, but therapy resistance occurs in up to a half of cases resulting in incurable advanced disease. We recently reported that ESR1 fusions are recurrent in endocrine resistant advanced breast cancer, and that these fusions show constitutive activity due to the lack of the ER hormone binding domain. In this proposal our cross-disciplinary team of breast cancer biologists, clinicians, and structural biologists will investigate the biology and clinical relevance of ESR1 fusions to develop information required for targeting this key mechanism of endocrine resistance.

PI_NAMEs: LEE, ADRIAN V (contact);OESTERREICH, STEFFI

PROJECT_TERMS: Adopted;advanced breast cancer;advanced disease;Amino Acids;Anti-estrogen Therapy;Base Pairing;Binding;Biological Assay;Biology;biophysical techniques;Biopsy;Breast Cancer cell line;Breast Cancer Model;C-terminal;Cell Line;Cell model;Cells;Clinical;clinically relevant;Code;cohort;Collection;Data;Detection;Development;Disease;DNA Binding;Drug Modelings;Drug resistance;Endocrine;Engineering;ESR1 gene;Estrogen Antagonists;Estrogen receptor positive;Estrogen Receptors;Estrogen Therapy;Estrogens;Evolution;Exons;fusion gene;gain of function;Gene Expression;Gene Fusion;Gene Rearrangement;Genes;Genetic Transcription;genome sequencing;genomic data;genomic locus;Genomics;Goals;Histologic;hormone therapy;Hormones;Hyperactivity;in vivo;insight;International;Introns;Ligand Binding;Ligands;Malignant Breast Neoplasm;MDA MB 435;Mediator;Messenger RNA;Metastatic breast cancer;Missense Mutation;Modeling;Molecular;Molecular Conformation;Monitor;mortality;multidisciplinary;Mutation;N-terminal;NF-kappa B;novel;novel therapeutics;Organoids;Pathway interactions;patient derived xenograft model;Patients;Plasma;Point Mutation;Prevalence;Prevention;promoter;Promoter Regions;Proteins;Recurrence;Reporting;Resistance;response;Role;Solid Neoplasm;Structural Biologist;Structure;Testing;Therapeutic Intervention;Transactivation;Translating;tumor;tumor DNA;whole genome;Xenograft procedure

PROJECT_TITLE: Estrogen receptor fusions genes as drivers of endocrine resistance in breast cancer

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


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

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Overexpression of USP36 and deregulated ribosome biogenesis and protein translation are associated with human cancers. This study aims at elucidating the role and mechanism of USP36 as a novel regulator of the nucleolar RNA exosome critical for ribosome biogenesis and will yield important insight into targeting USP36 and ribosome biogenesis for cancer therapy.

PI_NAMEs: DAI, MU-SHUI  (contact)

PROGRAM_OFFICER_NAME: MAAS, STEFAN

PROJECT_TERMS: Ablation;Adaptor Signaling Protein;Affect;Affinity Chromatography;Animals;Binding;Biochemical;Biogenesis;Breast Cancer Cell;cancer therapy;Cell Culture Techniques;Cell Cycle Progression;cell growth;Cell Nucleolus;Cell Physiology;Cell Proliferation;cell transformation;Cells;Cellular Stress;Complex;Data;Defect;design;Deubiquitinating Enzyme;DNA biosynthesis;DNA Repair;Endoribonucleases;Ensure;exosome;Genetic Transcription;Goals;Growth;Homeostasis;Human;Impairment;In Vitro;in vivo;in vivo Model;Inhibition of Cell Proliferation;insight;Investigation;knock-down;Knockout Mice;Lead;Ligase;Link;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Tumorigenesis;Mass Spectrum Analysis;Mediating;Modification;Molecular;mouse model;mutant;Mutate;Normal Cell;novel;Nuclear Export;Nuclear RNA;overexpression;Pathway interactions;Phosphodiesterase I;Physiological;Play;protein complex;Proteins;Quality Control;Regulation;Reporting;response;Ribosomal RNA;Ribosomes;RNA;RNA Degradation;RNA Processing;Role;Shapes;Side;Signal Transduction;Small Nucleolar RNA;Sumoylation Pathway;therapeutic target;Transgenic Mice;Translations;tumor;tumorigenesis;ubiquitin isopeptidase;Untranslated RNA

PROJECT_TITLE: Regulation of the nucleolar RNA exosome in cancer

STUDY_SECTION: MONC

STUDY_SECTION_NAME: Molecular Oncogenesis Study Section[MONC]


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

ORG_CITY: BLOOMINGTON

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: PUBLIC HEALTH RELEVANCE More than six million Americans suffer from neurodegenerative diseases, for which there are no good treatments. We are studying how a protein called NMNAT2 provides neuroprotection in the mammalian central nervous system with a long-term goal of developing therapies to treat neurodegenerative diseases, including Alzheimer's disease and Alzheimer’s disease related dementia.

PI_NAMEs: LU, HUI-CHEN  (contact)

PROGRAM_OFFICER_NAME: MCGAVERN, LINDA

PROJECT_TERMS: Acceleration;Age;age related decline;Aging;ALS patients;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease therapy;American;Amyloid beta-Protein;Amyloid beta-Protein Precursor;amyloid precursor protein processing;Attenuated;Axon;axonal degeneration;Axonal Transport;axonopathy;Bayesian Analysis;Biology;Brain;brain metabolism;Bypass;Central Nervous System;Chronic;cofactor;cognitive function;combat;Compensation;Data;Defect;design;Development;disease model;Down-Regulation;drug discovery;Energy Supply;Enzymes;Face;fast axonal transport;Financial cost;Genes;Genetic study;Gliosis;Glucose;glucose metabolism;Glutamate-ammonia-ligase adenylyltransferase;Glutamates;Glycolysis;Goals;Golgi Apparatus;Health;Hippocampus;Homeostasis;Human;Huntington Disease;Hyperactivity;hyperphosphorylated tau;Image;Impairment;in vivo;Inflammation;insight;Knockout Mice;Knowledge;Life;Link;Maintenance;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Molecular;Molecular Chaperones;Mus;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;Neurons;neuroprotection;Nicotinamide adenine dinucleotide;Nicotinamide Mononucleotide;nicotinamide riboside supplementation;novel;novel therapeutic intervention;Oxidative Phosphorylation;Parkinson Disease;Pathology;Pentosephosphates;Phenotype;Play;Prevalence;prevent;Process;programs;Proteins;Proteolytic Processing;public health relevance;Resolution;response;Risk Factors;Role;sensor;social;Spinal Cord;Supplementation;Synaptic Transmission;Synaptic Vesicles;synaptogenesis;tau Proteins;Testing;theories;Therapeutic;therapeutic target;therapy development;Time;Up-Regulation;Visualization

PROJECT_TITLE: Molecular and genetic studies of NMNAT2 in neuroprotection

STUDY_SECTION: CDIN

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


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

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

ORG_CITY: KINGSTON

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF RHODE ISLAND

ORG_STATE: RI

PHR: PROJECT NARRATIVE Neurodegenerative diseases such as ALS/FTD represent an outsized burden to a progressively aging world population, and no cure exists to alleviate symptoms or stop the progression of these diseases. The proposed research is expected to elucidate at the mechanistic level the novel molecular pathways underlying cellular pathology in human ALS/FTD neurons. We anticipate that this research will contribute to the identification of novel targets in these pathways for the development of innovative therapeutic strategies for ALS/FTD and potentially other neurodegenerative diseases.

PI_NAMEs: FALLINI, CLAUDIA  (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Actins;Adult;Affect;Aging;axonal degeneration;Binding;C9ORF72;Cell model;Cell Nucleus;Cells;cellular pathology;coping;CREB1 gene;Cytoplasm;Cytoskeleton;Defect;Dendrites;design;Development;Disease;Disease Progression;DNA;DNA Binding;DNA-Binding Proteins;Failure;familial amyotrophic lateral sclerosis;frontal lobe;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic approach;Genetic Transcription;Homeostasis;Human;Impaired cognition;Impairment;Induced pluripotent stem cell derived neurons;innovation;insight;Investigation;Knowledge;Lead;Link;Messenger RNA;Modeling;Molecular;Morphology;Motor Neurons;Muscle;Mutation;Nerve Degeneration;Neurodegenerative Disorders;neuron loss;neuronal survival;Neurons;novel;novel therapeutic intervention;Nuclear;Nuclear Import;Nuclear Lamina;Nuclear Pore Complex;nucleocytoplasmic transport;Outcome;Paralysed;Pathogenesis;Pathogenicity;Pathology;Pathway Analysis;Pathway interactions;pharmacologic;Phenotype;Physiological;Play;Population;postmitotic;Process;protein TDP-43;Proteins;Proteome;Proteomics;reduce symptoms;Regulation;Research;resilience;response;RNA;RNA Binding;RNA Splicing;RNA-Binding Proteins;Role;Spliced Genes;Stress and Coping;Structure;Synapses;Testing;Therapeutic;therapeutically effective;transcription factor;Transcriptional Activation;Transcriptional Regulation;transcriptome sequencing;transcriptomics;Translations

PROJECT_TITLE: Defining the Mechanisms and Consequences of Nuclear Defects in ALS/FTD

STUDY_SECTION: SYN

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


NIH_SPENDING_CATS: Cancer;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Rare Diseases

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

ORG_STATE: CA

PHR: Project Narrative Splicing factor SF3B1 gene is frequently mutated in chronic lymphocytic leukemia and these mutations significantly co-occur with a deletion of 11q (minimal deleted region contains ATM) as well as ATM mutations (loss-of-function). Our murine model confirmed that co-expression of heterozygous mutant Sf3b1 and deletion of Atm in B cells results in CLL onset. We thus propose to fully understand the molecular mechanisms of how RNA splicing dysregulation and impaired DNA damage signaling synergistically impact pathogenesis of CLL.

PI_NAMEs: WANG, LILI  (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: 11q;Acceleration;adult leukemia;aged;Alternative Splicing;ATM Gene Mutation;B-Lymphocytes;Biology;Blood;cancer cell;CD19 gene;Cell Aging;Cell Cycle Regulation;Cells;Chemoresistance;Chromosomal Instability;Chromosomes;Chronic Lymphocytic Leukemia;chronic lymphocytic leukemia cell;Clinic;Clinical Trials;Clonal Evolution;Clonal Expansion;CRISPR/Cas technology;cytotoxicity;Data;Dependence;design;Development;Disease Progression;DNA;DNA Damage;DNA damage checkpoint;DNA Repair;DNA Repair Pathway;DNA sequencing;early onset;Excision;Foundations;Frequencies;Genes;Genetic;genetic information;genome-wide;Genomic Instability;Genotype;Goals;Heterozygote;Hybrids;Impairment;in vivo;inhibitor;Introns;Knowledge;Lesion;Link;Literature;Location;loss of function;Malignant - descriptor;Marrow;Mitotic;Modeling;Molecular;mouse model;Mus;mutant;Mutate;Mutation;North America;novel;Pathogenesis;Pathway interactions;Patients;Pattern;Penetrance;peripheral blood;Phenotype;PTPRC gene;Publishing;Recurrence;replication stress;Research;response;RNA;RNA Splicing;Sampling;Signal Pathway;Signal Transduction;Site;Somatic Mutation;Spleen;Stress;Structure;Testing;treatment response;tumorigenesis;Variant;whole genome;Work;Yin

PROJECT_TITLE: Cooperation of SF3B1 mutations and ATM deletions in the pathogenesis of chronic lymphocytic leukemia

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


NIH_SPENDING_CATS: Cancer;Clinical Research;Digestive Diseases;Immunotherapy;Pancreatic Cancer;Rare Diseases

ORG_DEPT: SURGERY

PHR: NARRATIVE Notch signaling regulates pancreatic tumor epithelium. Its role in the tumor microenvironment is less clear. We will dissect compartment specific Notch signaling (Aim 1); study Notch-driven myeloid polarization of T cells (Aim 2), and test the role of Notch inhibition of T cell function and activity (Aim 3) in the pancreatic tumor microenvironment.

PI_NAMEs: BEDNAR, FILIP ;PASCA DI MAGLIANO, MARINA  (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: Apoptosis;Biological Assay;cancer initiation;Cause of Death;Cell Physiology;cell type;Cells;checkpoint inhibition;chemotherapy;Coculture Techniques;Combination immunotherapy;Complex;Cytotoxic T-Lymphocytes;Data;Development;Disease;disease model;early phase clinical trial;Embryo;Epithelial Cells;Epithelium;Erinaceidae;exhaust;experimental study;Fibroblasts;gamma secretase;Genes;Genetic;Genetic Engineering;Genetically Engineered Mouse;Goals;Human;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;Immune response;immunomodulatory therapies;Immunosuppression;Immunotherapy;In Vitro;in vivo;inhibitor;innovation;Ligands;Macrophage;Maintenance;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mediator;Modeling;mouse model;Mus;Myelogenous;Myeloid Cells;Nature;notch protein;novel;novel strategies;Organoids;Pancreas;pancreatic cancer model;pancreatic neoplasm;Pathway interactions;Patients;pharmacologic;Phenotype;polarized cell;Population;pre-clinical;Regulatory Pathway;Role;Sampling;Signal Pathway;Signal Transduction;T-Lymphocyte;Testing;therapy resistant;transplant model;Transplantation;tumor;Tumor Cell Line;tumor growth;tumor initiation;tumor microenvironment;tumor progression;Tumor-associated macrophages;tumor-immune system interactions;United States;Work

PROJECT_TITLE: Dissecting the role of Notch signaling in the pancreatic cancer microenvironment.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-S(02)M]


NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Disability Research;Lung;Neurosciences;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Rehabilitation;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: CLEVELAND

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: We propose to develop an implanted device that can measure health status and, in a future study, test this system in individuals with spinal cord injury (SCI) to determine if early prediction of disease states can increase life expectancy. The proposed implanted device, called the Lifeline, measures parameters such as body temperature, photoplethysmogram, electrocardiogram, sound, and acceleration. Taken together, these measures may be able to predict the early onset of autonomic dysreflexia (specific to SCI), pneumonia, urinary tract infections, and pulmonary embolism, which are among the top causes of death in SCI.

PI_NAMEs: KILGORE, KEVIN L. (contact)

PROGRAM_OFFICER_NAME: BITTMANN, MORIA FISHER

PROJECT_TERMS: Acceleration;Acoustics;Applications Grants;Autonomic Dysreflexia;Autonomic nervous system;Benefits and Risks;Biomedical Engineering;Blood Vessels;Body Temperature;Cause of Death;Clinical Research;Computer software;cost;Data;Data Storage and Retrieval;design;Development;Devices;Disease;Early Diagnosis;early onset;Electric Stimulation;Electrocardiogram;Electronics;Event;expectation;Foundations;functional improvement;Future;Goals;Guidelines;Health;health data;Health Status;Human;Implant;implantable device;implantation;improved;in vitro testing;in vivo;Individual;insight;Intervention;Life;Life Expectancy;Measurement;Measures;Mechanics;Medical;Monitor;monitoring device;mortality;Motor;multimodality;neuroprosthesis;operation;Operative Surgical Procedures;Optics;Outcome;Output;Persons;Pneumonia;Populations at Risk;prototype;Pulmonary Embolism;Quadriplegia;Quality of life;Relative Risks;research clinical testing;Research Project Grants;Risk;Risk-Benefit Assessment;sensor;Signal Transduction;sound;Source;Specific qualifier value;Spinal cord injury;surgical risk;System;Temperature;Temperature Sense;Testing;Time;Urinary tract infection;wireless data transmission

PROJECT_TITLE: Augmenting Implanted Neuroprosthetics with Targeted Health Monitoring for Spinal Cord Injury - the LIFELINE


ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative Thrombocytopenia is a major clinical problem encountered in multiple conditions, and severe thrombocytopenia (platelet counts <50 x 109/L) can lead to life threatening bleeding. We have discovered a novel regulator of megakaryocyte maturation and platelet production during inflammation: platelet-derived microvesicles in the bone marrow. Targeting 1) the generation of microvesicles from platelets and/or 2) the interactions between microvesicles and megakaryocytes may allow development of novel ways modify platelet production in patients with thrombocytopenia or thrombocytosis.

PI_NAMEs: MACHLUS, KELLIE RAE (contact)

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: Acute;Address;Agonist;Binding;Biogenesis;Biology;Blood Platelets;blood product;Bone Marrow;Bone Marrow Cells;Cardiovascular Diseases;Cell Communication;Cell membrane;Cells;Clinical;Collagen;Data;Dependence;Development;Disease;Environment;experimental study;extracellular vesicles;Family;Gene Expression;Generations;Goals;Hematopoietic;Hemorrhage;Human;In Vitro;in vivo;Inflammation;Inflammatory;inhibitor;insight;Knowledge;Life;Link;Mediating;Megakaryocytes;Megakaryocytopoieses;member;Membrane Fusion;Messenger RNA;MicroRNAs;microvesicles;mimetics;Modeling;Monomeric GTP-Binding Proteins;Morbidity - disease rate;mortality;Mothers;Mus;new therapeutic target;novel;Outcome Study;Pathogenicity;Pathologic;Pathway interactions;Patients;Plasma;Platelet Activation;Platelet Count measurement;prevent;Production;Property;Regulation;Research;response;rho;rho GTP-Binding Proteins;side effect;Signal Transduction;Steroids;Systemic Lupus Erythematosus;Therapeutic Intervention;Thrombin;Thrombocytopenia;thrombocytosis;Thrombopoiesis;Thrombopoietin;Time;Transcript;transcription factor;transcriptome;Up-Regulation;uptake

PROJECT_TITLE: The Biogenesis of Platelet-Derived Extracellular Vesicles and their Impact on Megakaryocyte Maturation

STUDY_SECTION: HT

STUDY_SECTION_NAME: Hemostasis and Thrombosis Study Section.  Committee was terminated on 11/30/2020. [HT]


ED_INST_TYPE: SCHOOLS OF PHARMACY

PHR: The first goal of this research is to develop systematic methods for generating affinity molecules (antibodies) that specifically target different types of toxic and highly complex protein particles (aggregates) linked to Parkinson’s disease and other neurodegenerative diseases. The second goal is to use the novel antibodies generated in this work to understand key structural differences between unique types of toxic protein aggregates that are linked to and potentially cause different neurodegenerative diseases. These findings are expected to improve the diagnosis, evaluation and potentially the treatment of diverse neurodegenerative diseases.

PI_NAMEs: TESSIER, PETER M (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Affinity;alpha synuclein;Antibodies;antibody libraries;Antibody Specificity;Antigens;Bioinformatics;Biological;Biological Phenomena;design;Diagnosis;Diagnostic;Disease;Disparate;Epitopes;Evaluation;Event;Generations;Goals;Human;Hydrophobicity;Immunodominant Epitopes;improved;In Vitro;in vivo;insight;Kinetics;Libraries;Link;Mediating;Methodology;Methods;Microbial Biofilms;Molecular Conformation;Monoclonal Antibodies;Neurodegenerative Disorders;novel;Parkinson Disease;particle;Prions;protein aggregation;protein complex;Proteins;Research;Sorting;Specificity;stem;Structure;Therapeutic Agents;three dimensional structure;Variant;Work;Yeasts

PROJECT_TITLE: Structure-guided antibody targeting of pre-selected epitopes in amyloidogenic aggregates

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


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

ORG_CITY: ATLANTA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative As the burden of Alzheimer’s disease in the United States and worldwide is high, there is a critical need to develop novel PET ligands to image illness-related biological processes in the brain. This work will develop key imaging tools designed to advance the scientific understanding of subtype-specific NMDA receptors in the ionotropic glutamate system and facilitate the discovery of neurotherapeutics for Alzheimer’s disease patients.

PI_NAMEs: LIANG, STEVEN H (contact)

PROGRAM_OFFICER_NAME: GROTHAUS, PAUL G

PROJECT_TERMS: ABCB1 gene;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;antagonist;aspartate receptor;Autopsy;Autoradiography;Binding;Binding Proteins;Biochemical Process;Biodistribution;Biological;Biological Assay;Biological Process;Blood specimen;Brain;brain tissue;Clinical;clinical translation;design;Development;Docking;Dose;drug discovery;Evaluation;Functional disorder;Generations;glutamatergic signaling;Glutamates;Goals;Human;Image;image translation;Imaging Device;imaging study;improved;In Vitro;in vitro Assay;in vivo;in vivo evaluation;Kinetics;Knowledge;Label;Lead;Ligands;lipophilicity;Liver Microsomes;Metabolism;Midbrain structure;Modeling;Molecular;Monitor;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;Neurodegenerative Disorders;next generation;nonhuman primate;novel;Parents;Patients;Penetration;Permeability;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;pharmacologic;Plasma;Plasma Proteins;Pontine structure;Positron-Emission Tomography;Public Health;Radioactivity;Radiolabeled;radioligand;Reaction;receptor;response;Rodent;Scientific Advances and Accomplishments;Series;Site;Specificity;Standardization;Synaptic plasticity;System;Testing;Therapeutic;Toxic effect;Translations;United States;uptake;Validation;Work;ylide

PROJECT_TITLE: Subtype-selective NMDA ligands for Alzheimer's Disease

STUDY_SECTION: DDNS

STUDY_SECTION_NAME: Drug Discovery for the Nervous System Study Section[DDNS-R]


PHR: PROJECT NARRATIVE The proposed project aims to define the molecular mechanisms of an error-prone, stress-induced Okazaki fragment maturation (OFM) pathway by which cancer cells counteract DNA replication stress and survive. Better understanding of these mechanisms may provide a strategy to guide the development of therapies that prevent or overcome therapeutic resistance.

PI_NAMEs: SHEN, BINGHUI  (contact)

PROGRAM_OFFICER_NAME: WEINREICH, MICHAEL DALE

PROJECT_TERMS: 3'-nuclease;acquired drug resistance;anti-cancer;Applications Grants;cancer cell;Cancer Model;cancer therapy;Cell Death;Cell Maturation;Cell Proliferation;Cell Senescence Induction;Cell Survival;Cells;CHEK1 gene;CHEK2 gene;chemotherapy;Data;DNA biosynthesis;DNA Damage;DNA damage checkpoint;DNA Sequence Alteration;Drug resistance;Enzymes;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Evolution;Genetic Screening;genome-wide;Genomic Segment;Goals;Growth;helicase;Human;Impairment;In Vitro;in vitro activity;lung cancer cell;Malignant Epithelial Cell;Mammalian Cell;Measures;Modeling;Molecular;mouse model;Mus;Mutagenesis;mutant;Mutate;Mutation;Non-Small-Cell Lung Carcinoma;nuclease;Okazaki fragments;Pathway interactions;Phosphorylation;prevent;Probability;Process;Radiation therapy;recruit;replication stress;Resistance;response;Role;RTH-1 Nuclease;Signal Induction;Signal Transduction;Site;Stress;Structure;Supporting Cell;Temperature;Testing;therapy development;therapy resistant;yeast genetics;Yeasts

PROJECT_TITLE: Okazaki fragment maturation: mutagenesis and cell survival

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


NIH_SPENDING_CATS: Assistive Technology;Autoimmune Disease;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Physical Activity;Prevention

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Biobehavioral Human-Machine Co-Adaptation of the Artificial Pancreas Large-scale artificial pancreas studies, including a multi-center pivotal trial recently completed by our team, have established the current capabilities of closed-loop control (CLC) and identified its deficiencies, e.g. inferior control during the day due to slow insulin response to fast biobehavioral perturbations. We therefore propose to develop and test a next-generation CLC system – Adaptive Biobehavioral Control (ABC) based on the novel concept of human-machine co-adaptation – which will use a stochastic-process approximation of the day-to-day variation in human physiology and behavior to individualize and optimize CLC. The ABC concept recognizes both the necessity for the control algorithm to adapt to changes in human physiology and the necessity for the person to adapt to CLC action; thus, ABC is expected to be superior to current state-of-the art CLC systems in terms of glycemic control outcomes, particularly during the day, and technology acceptance by the user.

PI_NAMEs: BROWN, SUE A;KOVATCHEV, BORIS P (contact)

PROGRAM_OFFICER_NAME: ARREAZA-RUBIN, GUILLERMO

PROJECT_TERMS: Address;advanced system;Algorithm Design;Algorithms;Artificial Pancreas;Behavior;Behavior Control;Behavior Therapy;Behavioral;biobehavior;Blood Glucose;Caring;Cellular Phone;Classification;Clinic;clinical practice;Clinical Trials;Code;Color;Continuous Glucose Monitor;control trial;Cross-Over Trials;Crossover Design;Data;Databases;design;Development;Diabetes Mellitus;efficacy evaluation;Enrollment;Exercise;experience;Funding;Generations;Glucose;glycemic control;Goals;Human;Hyperglycemia;Hypoglycemia;hypoglycemia unawareness;improved;Incidence;Inferior;Insulin;Insulin Infusion Systems;Insulin-Dependent Diabetes Mellitus;Journals;Learning;Measures;Medicine;metabolic profile;mobile application;Modality;Monitor;New England;next generation;novel;Outcome;Participant;Persons;Physical activity;Physiological;Physiological Adaptation;Physiology;pilot test;preference;preservation;Procedures;Process;Publishing;Randomized;randomized trial;Recording of previous events;Research;response;Risk;Risk Assessment;Self Management;Stochastic Processes;System;Technology;Testing;Time;Translating;trial comparing;trial enrollment;United States National Institutes of Health;Variant;virtual;Work

PROJECT_TITLE: Biobehavioral Human-Machine Co-adaptation of the Artificial Pancreas

STUDY_SECTION: CIDO

STUDY_SECTION_NAME: Clinical and Integrative Diabetes and Obesity Study Section[CIDO]


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Genetics;Infectious Diseases;Neurosciences;Pediatric;Precision Medicine;Prevention

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: PROJECT NARRATIVE Viral infections in the prenatal brain lead to severe injury and neurodevelopmental disorders, including cerebral palsy, global developmental delay, epilepsy, and other life-shortening disabilities. Currently, there are no preventive strategies and only few targeted therapies are available for prenatal viral infections. This work will investigate how two neuroviral candidate genes, mTOR and HEXB, regualte prenatal viral autophagy and neuronal survival by integrating novel systems modeling, lab studies, and clinical analyses; its long-term goal is to identify precision therapies for mitigating viral and other risks to the developing prenatal brain.

PI_NAMEs: KOUSA, YOUSSEF A (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Affect;Alleles;Animals;Autophagocytosis;Award;beta-n-acetylhexosaminidase;Biological Models;Board Certification;Brain;Brain Injuries;Candidate Disease Gene;career development;Caring;Cell Physiology;Cell Survival;Cerebral Palsy;Cerebrum;Child;Childhood;Clinical;Clinical Data;clinical phenotype;Code;Complex;Country;Critical Care;Data;Development;Development Plans;disability;Dizygotic Twins;Epilepsy;exome sequencing;follow-up;FRAP1 gene;Future Generations;Gene Expression;Genes;Genetic;Genomics;global developmental delay;Goals;Grant;Health;Hospitals;Human;humanized mouse;Image;in vivo;Individual;Infant;infant infection;Infection;International;Internships;knock-down;Lead;Life;Life Experience;loss of function;loss of function mutation;Loss of Heterozygosity;Lysosomes;member;Mentors;Modeling;Mothers;Motor;Motor Cortex;mouse model;Mus;National Institute of Neurological Disorders and Stroke;Neonatal;nerve stem cell;Neurobiology;neurodevelopment;Neurodevelopmental Disability;Neurodevelopmental Disorder;Neuroepidemiology;Neurologist;Neuronal Injury;neuronal survival;Neurons;neuropathology;Neuropsychology;Neurovirology;novel;Organoids;Outcome;overexpression;pandemic disease;Pathway interactions;PI3K/AKT;Population;Positioning Attribute;postnatal;postnatal development;precision medicine;Precision therapeutics;Predisposition;Pregnancy;prenatal;prevent;Prevention;Prevention strategy;Proteins;public-private partnership;Regulation;Research;Research Infrastructure;Research Personnel;response;Risk;Role;Scientist;Seasons;Secure;Series;severe injury;single-cell RNA sequencing;Study Subject;System;targeted treatment;Testing;Therapeutic Intervention;Titrations;Training;transcriptome sequencing;United States National Institutes of Health;Variant;Viral;Viral Load result;Virus;Virus Diseases;Virus Replication;Western Blotting;Work;ZIKA

PROJECT_TITLE: Viral Neurobiology in the Prenatal Brain

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]