NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Heart Disease;Patient Safety;Physical Activity;Physical Rehabilitation;Prevention;Rehabilitation;Social Determinants of Health;Telehealth

ORG_CITY: PROVIDENCE

ORG_NAME: MIRIAM HOSPITAL

ORG_STATE: RI

PHR: PROJECT NARRATIVE Cardiac rehabilitation (CR) is an evidence-based, available, reimbursable treatment for cardiovascular disease (CVD) that reduces secondary cardiovascular risk, but adherence to cardioprotective behaviors established during CR (weight management, physical activity [PA], medication adherence) diminish with time effectively furthering health disparities in cardiovascular care; this represents a public health crisis. This study will use the Sequential Multiple Assignment Randomized Trial (SMART) design to develop an adaptive stepped-care intervention sequence for 400 under-resourced or under-represented CR patients following CR graduation intended to rescue patients from non-adherence and preserve cardioprotective behavior engagement. The technology-based interventions will be evaluated across 6 months, and the primary outcome is to determine the best intervention for adherent and non-adherent patients measured by adherence to the 3 key behaviors.

PI_NAMEs: GOLDSTEIN, CARLY MICHELLE (contact)

PROGRAM_OFFICER_NAME: SHIROMA, ERIC JITSUO

PROJECT_TERMS: Accreditation;Acute;adaptive intervention;Address;Adherence;Adult;Affect;Behavior;Cardiac rehabilitation;cardioprotection;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;Caring;Case Management;Cause of Death;Cessation of life;Classification;Clinical;compliance behavior;cost effective;disabled;Dose;Education;effective intervention;Enrollment;ethnic minority;evidence base;Exercise;exercise prescription;Expenditure;experience;Face;Failure;Feedback;flexibility;follow-up;Goals;Health;Health behavior;Health behavior change;health disparity;Home;hospital readmission;improved;Individual;Inequity;Insurance;Intervention;low socioeconomic status;Maintenance;Measures;Medicare/Medicaid;medication compliance;Methodology;Modeling;Monitor;multidisciplinary;online delivery;online intervention;Outcome;Outcome Assessment;Participant;Patient Noncompliance;Patient-Focused Outcomes;Patients;personalized approach;Persons;Phase;Physical activity;Planning Theory;post intervention;preference;preservation;primary outcome;Privatization;programs;psychoeducation;Public Health;Quality of life;racial minority;Randomized;rehabilitation research;rehabilitative care;Research;research to practice;Resistance;Resources;responders and non-responders;Risk Factors;Schedule;Science;Sequential Multiple Assignment Randomized Trial;social cognitive theory;standard care;success;Technology;technology intervention;Testing;Text Messaging;text messaging intervention;Time;Touch sensation;trial design;Underserved Population;United States;Weight Gain;Weight maintenance regimen;Woman;Work

PROJECT_TITLE: An Application of SMART Methodology to Optimize an Intervention to Maintain Improvements in Health Behaviors in Under-resourced Patients after Phase II Cardiac Rehabilitation

STUDY_SECTION: CMGC

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


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: LOS ANGELES

ORG_COUNTRY: UNITED STATES

ORG_DEPT: CHEMISTRY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: Project Narrative Microbial pathogens display proteins, pili, and glycopolymers that are important for their viability and pathogenicity. We will elucidate the molecular mechanisms that underpin the display of these macromolecules in gram-positive bacteria. Chemical libraries that sum to more than 200,000 small molecules will be screened using a novel cell-based assay to identify glycopolymer assembly inhibitors that could be developed into antibiotics.

PI_NAMEs: CLUBB, ROBERT THOMPSON (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Active Sites;Adherence;Adhesives;Affect;Anabolism;Antibiotics;Bacteria;Bacterial Infections;base;beta-Lactams;Binding;Biochemical;Biogenesis;Biological Assay;Cell surface;Cell Wall;Cells;Chemicals;Chemistry;Clinical;Complement;Complex;Computational Biology;Corynebacterium diphtheriae;crosslink;Cryoelectron Microscopy;Data;Development;Diphtheria;Drug resistance;drug resistant bacteria;Drug Targeting;Enterococcus faecium;Environment;Enzymes;Epithelium;Fimbriae Proteins;Goals;Gram-Positive Bacteria;Growth;high throughput screening;Homeostasis;Impairment;improved;Infection;inhibitor;insight;interdisciplinary approach;Learning;Licensing;Link;Lysine;macromolecule;Mass Spectrum Analysis;Membrane;methicillin resistant Staphylococcus aureus;Methods;microbial;Microbiology;Molecular;mosaic;N-acetylmannosamine;novel;novel therapeutics;pathogen;pathogenic bacteria;pathogenic microbe;Pathogenicity;Peptidoglycan;Pharyngeal structure;Pilum;Polymerase;polymerization;Polymers;Process;Protein Subunits;Proteins;Proteome;Proteomics;Reaction;Research;Respiratory Disease;Site;small molecule;small molecule libraries;Staphylococcus aureus;Streptococcus pneumoniae;Structural Biochemistry;Structure;Structure-Activity Relationship;Sum;Surface;Synthesis Chemistry;Teichoic Acids;Tensile Strength;Thick;Tissues;Transferase;Virulence;Virulence Factors

PROJECT_TITLE: Cell Surface Polymer Display in Gram-Positive Bacteria

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Infectious Diseases;Primary Immunodeficiencies;Rare Diseases

ORG_CITY: CORAL GABLES

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Narrative Currently, hidradenitis suppurativa (HS) is the most devastating disease in dermatology, with tunnel formation resulting in a major impact to patients’ quality of life and significant burden and associated costs to the health care system. Our long-term goal is to develop targeted therapies that can restore function of the tissue and prevent disease progression. Better understanding of the mechanisms that control local tissue cortisol synthesis and signaling in HS tunnels, coupled with the novel 3D organoid HS model will facilitate a clear path to translating this knowledge to develop novel advanced therapeutic approaches for HS.

PI_NAMEs: LEV-TOV, HADAR ;PASTAR, IRENA ;TOMIC-CANIC, MARJANA  (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: 3-Dimensional;Abscess;Adrenal Glands;Affect;Age;Agonist;antagonist;Anti-Inflammatory Agents;Antiinflammatory Effect;Apoptosis;Automobile Driving;Binding;Biology;cell motility;cell type;Cells;Characteristics;Chronic;clinically relevant;comparative;Complement;Corticotropin;cost;Coupled;CRISPR/Cas technology;Cultured Cells;Cutaneous;Cytoplasm;Cytoskeleton;Data;Dermal;Dermatology;Development;Disease;Disease Progression;Down-Regulation;effective therapy;Epithelium;Ethnic Origin;Fibroblasts;Functional disorder;functional restoration;Gender;Gene Expression;Gene Modified;genetic regulatory protein;Genomics;Glucocorticoid Receptor;Glucocorticoids;Goals;healing;Healthcare Systems;Hidradenitis Suppurativa;Hydrocortisone;Hypoxia;Inflammation;Inflammatory;Inflammatory Response;Injury;insight;Interleukin-1 beta;keratinocyte;Knock-in;Knock-out;Knowledge;Location;Measures;Mediating;Membrane;migration;Modeling;multidisciplinary;Nodule;non-genomic;normoxia;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Nuclear;Organoids;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;Phenotype;Physiological;Plasma;Play;prevent;Prevention approach;Process;Production;Publishing;Quality of life;Race;Receptor Activation;Receptor Signaling;Regulation;response;restraint;Role;Sampling;sex;Signal Transduction;Sinus;Skin;skin disorder;Source;Specimen;stem;Steroid biosynthesis;Steroids;Structure;targeted treatment;Testing;Therapeutic;three-dimensional modeling;tissue repair;Tissue Sample;Tissues;transcriptomics;Translating;treatment strategy;wound healing

PROJECT_TITLE: The role of cortisol synthesis in pathogenesis of Hidradenitis suppurativa tunnels

STUDY_SECTION: ACTS

STUDY_SECTION_NAME: Arthritis, Connective Tissue and Skin Study Section[ACTS]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Nutrition;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: NARRATIVE. The lack of knowledge about the glucose transporter responsible for intestinal stem cell (ISC) basal glucose uptake has hampered mechanistic investigations into the influence of glucose on their homeostasis. Here, we will investigate the role of GLUT1 and glucose in ISC function in homeostasis and regeneration.

PI_NAMEs: SAEIDI, NIMA  (contact)

PROGRAM_OFFICER_NAME: GREENWEL, PATRICIA

PROJECT_TERMS: Ablation;absorption;Achievement;Address;Affinity;Basal Cell;Bile Acids;Biological Assay;Blood Glucose;Cell Count;Cells;Citric Acid Cycle;Colon;Data;Dependence;Diabetes Mellitus;diabetic;dietary;Enzymes;Epithelial Cells;Epithelium;epithelium regeneration;Etiology;Eukaryotic Cell;Exhibits;Fatty Acids;feeding;follow-up;Follow-Up Studies;G6PD gene;Generations;Genetic;Glucose;glucose metabolism;Glucose Transporter;glucose uptake;Glucosephosphates;GLUT-2 protein;Glycolysis;Goblet Cells;Growth;Homeostasis;Hyperglycemia;improved;in vitro regeneration;in vivo;in vivo regeneration;Inflammatory Bowel Diseases;Injury;inorganic phosphate;intestinal epithelium;intestinal injury;Intestines;Investigation;irradiation;Ketone Bodies;Knockout Mice;Knowledge;LGR5 gene;Maintenance;Maps;Mediating;Metabolic;Metabolic Control;Metabolism;metabolomics;Modeling;Mucous body substance;Mucous Membrane;Mus;Natural regeneration;notch protein;Nucleosides;Organoids;Pathologic;Pathway interactions;Pentosephosphate Pathway;Play;Predisposition;Production;Proliferating;Recovery;Regenerative capacity;Reporting;Role;Signal Pathway;SLC2A1 gene;Small Intestines;small molecule;Sodium;Starvation;stem cell function;stem cell homeostasis;stem cell self renewal;stem cells;stemness;Supplementation;symporter;System;Testing;Tracer;Transgenic Mice;tumorigenesis

PROJECT_TITLE: The Role of GLUT1 and Glucose in Intestinal Stem Cell Homeostasis and Regeneration

STUDY_SECTION: DNPD

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


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Diabetes;Digestive Diseases;Hepatitis;Liver Disease;Nutrition;Obesity

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: This proposal investigates whether complete or selective hepatic insulin resistance combines T2D (type 2 diabetes) with NAFLD (nonalcoholic fatty liver disease) that progresses to life-threatening NASH (nonalcoholic steatohepatitis). We use genetic and metabolomic approaches in mice fed a western GAN diet or a related high fructose diet, which model the sugar-sweetened food and beverages associated with T2D and NAFLD/NASH in people. Our experiments investigate whether Follistatin secreted from the insulin resistant liver integrates NAFLD/NASH with glucose intolerance of type 2 diabetes.

PI_NAMEs: WHITE, MORRIS F. (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: Acceleration;Adipocytes;Adipose tissue;alpha-glycerophosphoric acid;Antibodies;Attenuated;Beverages;Body fat;Bypass;Chronic;Clinical;Data;Dependence;diabetic;Diet;dietary;dietary excess;Disease Progression;Economic Burden;Energy Metabolism;Epidemic;Esterification;Expenditure;experimental study;Fatty acid glycerol esters;Fatty Acids;feeding;Femur;Follistatin;Food;FOXO1A gene;Fructose;Gene Expression;Genetic;Genetic Transcription;Glucose Intolerance;glucose output;glucose production;Glycerol;Health;Hepatic;Hepatocyte;High Fat Diet;Human;human data;Impairment;In Vitro;Inflammatory;Insulin;Insulin Receptor;insulin receptor substrate 1 protein;Insulin Resistance;insulin secretion;insulin signaling;islet amyloid polypeptide;Ketohexokinase;Label;Life;lipid biosynthesis;Lipids;Lipodystrophy;Lipolysis;Liver;Liver diseases;liver inflammation;Mediating;Metabolic;Metabolic Diseases;Metabolism;metabolomics;Modeling;mouse genetics;Mus;Non obese;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;Nutrient;Obesity;Overweight;Pathway interactions;patient subsets;Patients;Peripheral;Persons;Phenotype;Phosphorylation;Physiological;PIK3CG gene;prevent;protective effect;Risk;Role;Signal Transduction;Source;sugar;Thinness;Transcriptional Regulation;Transgenic Mice;Transgenic Organisms;Triglycerides

PROJECT_TITLE: Hepatic insulin resistance integrates T2D and NAFLD

STUDY_SECTION: POMD

STUDY_SECTION_NAME: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]


ADMINISTERING_IC: DC

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Clinical Research;Health Services;Lung;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Telehealth

ORG_CITY: PASADENA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE Voice and upper airway (VUA) diseases hamper a person’s speaking and breathing functions when performing day-to-day activities. In this project, we will develop a flexible, wireless wearable device to monitor VUA symptoms via a unique, hybrid accelerometry and electromyography sensing technology. With this new wearable system, clinicians will be able to track patient VUA health conditions outside clinics, whereas patients will be empowered to be more in charge of their health.

PI_NAMEs: GAO, WEI  (contact);LI, JIANYU ;LI-JESSEN, NICOLE YEE-KEY

PROGRAM_OFFICER_NAME: KOPF, LISA MARIE

PROJECT_TERMS: Accelerometer;Accountability;Acoustics;Adherence;Adhesions;Adhesives;Adopted;Adult;Affect;Airway Disease;Algorithms;Animal Testing;Behavior;Behavioral;Biocompatible Materials;Biological Markers;biomaterial compatibility;Breathing;care delivery;Charge;Chemicals;Chronic;Classification;Clinic;Clinical;clinically relevant;clinically significant;Communication;Companions;Coughing;Data;Data Collection;data exchange;data management;Deglutition;design;Development;Devices;Disease;Dose;Dryness;Electrodes;Electromyography;Electronics;empowerment;Engineering;Evaluation;Exercise;experience;Fatigue;Feedback;flexibility;flexible electronics;Frequencies;Functional disorder;Gel;General Population;Goals;Health;Health Care Costs;Health Status;Hoarseness;Human;Hybrids;improved;Individual;innovation;integrated circuit;irritation;Laboratories;Laryngeal muscle structure;Larynx;Life;Machine Learning;machine learning model;Measurement;Measures;Mechanics;Medicine;Miniaturization;mobile application;Modality;Monitor;multimodality;Muscle;Muscle Fatigue;Neck;Occupational;Outcome;Outcome Study;Participant;Patient Compliance;patient engagement;patient population;Patients;Pattern;Peripheral;Persons;Physiological;portability;Precision therapeutics;Preventive care;printed circuit board;productivity loss;Protocols documentation;Readiness;remote monitoring;remote patient monitoring;Research Personnel;respiratory health;Respiratory Muscles;Respiratory Signs and Symptoms;Self Management;sensor;sensor technology;Severities;Shapes;Sick Leave;Signal Transduction;Skin;skin patch;smartphone application;Speech;Surface;Symptoms;System;Technology;telehealthcare;Therapeutic;Time;Tissues;Translations;Treatment outcome;United States;Update;usability;vibration;Voice;Voice Quality;wearable data;wearable device;wearable platform;wireless;Work

PROJECT_TITLE: Develop a wireless, skin-conformable and dual-sensing wearable system in support of voice and upper airway telehealth care

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Eye Disease and Disorders of Vision;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Project Narrative Autism affects the brain’s capacity to interpret and respond to social information, including human faces. In this project, we use advanced imaging methods to measure the structure and connectivity of the part of the visual cortex that responds preferentially to faces in each individual, and how these measures of brain anatomy relate to face recognition ability. By focusing on brain structure and individually defined regions, rather than brain function and group averages, we hope to fill significant gaps in our knowledge and to shed light on the developmental mechanisms by which early visual experience shapes the social brain in autism.

PI_NAMEs: CASCIO, CARISSA J;MCGUGIN, RANKIN W;NEWTON, ALLEN T;SMITH, JOSHUA R (contact)

PROGRAM_OFFICER_NAME: GILOTTY, LISA

PROJECT_TERMS: Adult;adult with autism spectrum disorder;Affect;Anatomy;Anisotropy;Anterior;Atlases;Attention;autism spectrum disorder;behavior prediction;biomarker identification;Brain;Brain region;Categories;Clinical;comparison group;Complex;Data;density;Development;Diffuse;Diffusion Magnetic Resonance Imaging;Early Diagnosis;early experience;Emotional;experience;Face;face perception;Face Processing;Fiber;fusiform face area;Fusiform gyrus;gray matter;high resolution imaging;Human;Image;imaging modality;Impairment;improved;Individual;individual variation;Inferior;insight;Intervention;Knowledge;Lateral;Learning;Light;Magnetic Resonance Imaging;Maps;Measures;Mediating;Memory;Meta-Analysis;Methods;Motivation;myelination;neural;neural circuit;Neurites;neuromechanism;Neuronal Plasticity;novel;object perception;Occipital lobe;Outcome Study;Pattern;Perceptual learning;Performance;Pervasive Development Disorder;Process;Property;Radial;Recording of previous events;Research;Resolution;response;sample fixation;Shapes;social;social cognition;social skills;Specificity;Stimulus;Structure;synaptic pruning;System;Temporal Lobe;Thick;Thinness;timeline;ultra high resolution;Uncertainty;Visual;Visual Cortex;Visual Perception;Visual System;white matter;Work

PROJECT_TITLE: Ultra-high resolution imaging of category-selective visual cortex in autism

STUDY_SECTION: CPDD

STUDY_SECTION_NAME: Child Psychopathology and Developmental Disabilities Study Section[CPDD]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Antimicrobial Resistance;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: AMHERST

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

ORG_STATE: NY

PHR: PROJECT NARRATIVE: Cocktails of individually efficacious phages have been proposed as a strategy to create clinically viable phage therapeutics with sufficient spectrum of activity to combat highly resistant Pseudomonas aeruginosa. As such, this project will generate a highly optimized N-phage cocktail using a hybrid machine learning-pharmacokinetic/pharmacodynamic paradigm to strategically select N-phage components, dose, and administration schedule to maximize the killing of multi- and extensively-drug resistant Pseudomonas aeruginosa. This project will leverage phage whole-body distribution from our murine pneumonia model to establish a human, physiologically based pharmacokinetic model, which will allow detailed assessment of expected human exposures to phage and describe key aspects of target-mediated phage distribution.

PI_NAMEs: SMITH, NICHOLAS MICHAEL (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Address;Affinity;Antibiotic Resistance;Antibiotics;antimicrobial;Antimicrobial Resistance;Awareness;Bacteria;bacterial resistance;bactericide;Bacteriophages;Binding;Biological Assay;Biological Models;Biological Products;Blood;Clinical;clinically relevant;combat;Combined Antibiotics;Communities;Complex;Consensus;Culture Media;Data;Development;Dose;drug action;drug development;drug disposition;Drug Kinetics;Drug resistant Pseudomonas aeruginosa;Engineering;Epithelium;Exhibits;experimental study;exposed human population;Exposure to;extensive drug resistance;Fiber;Generations;Genes;Health;Heterogeneity;High Prevalence;Hospitals;Human;Hybrids;Immunocompromised Host;improved;In Vitro;in vivo;indexing;Individual;individual patient;Infection;innovation;Investigational New Drug Application;Knowledge;Liquid substance;Lung;Machine Learning;Mediating;Methods;microbiome;model building;Modeling;Modernization;Modification;mortality;Mus;nanoscale;novel;novel strategies;pandemic disease;Pattern;Peripheral;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetic model;pharmacokinetics and pharmacodynamics;Physiological;physiologically based pharmacokinetics;pneumonia model;pre-clinical;Proliferating;Property;Pseudomonas aeruginosa;Pseudomonas Phages;Public Health;Publishing;Qualifying;receptor;Regimen;Reporting;Resistance;response;Salvage Therapy;Sampling;Schedule;Site;Species Specificity;Specificity;Structure;synergism;Testing;Therapeutic;Time;Tissues;Toxic effect;Translating;Translations;transposon sequencing;treatment strategy;United States;Virulence;Whole Blood

PROJECT_TITLE: Pharmacokinetics and Pharmacodynamics of Mechanistically Aware Phage Cocktails

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MCST-M (81)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: SAINT LOUIS

ORG_DEPT: PATHOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Leigh Syndrome (LS) is an inherited mitochondrial disease that presents with prominent neurologic symptoms and death in childhood, with no effective therapies for this devastating disease currently available. Recent studies by our laboratory (Brestoff et al., Cell Metabolism, 2021) and other groups indicate that many cell types transfer their mitochondria to other cells in vivo, and our recent work demonstrates that administering healthy mitochondria to Ndufs4-deficient mice with LS completely restores cell-intrinsic metabolic defects (Borcherding et al., Cell Metabolism, 2022). The proposed studies will leverage our expertise in intercellular mitochondria transfer to establish two novel therapeutic strategies - postnatal mitochondria administration (Aim 1) and bone marrow transplantation (Aim 2) - to treat fatal inherited mitochondrial diseases such as LS.

PI_NAMEs: BRESTOFF, JONATHAN R (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Affect;Biodistribution;Biological;Bone Marrow;Bone Marrow Cell Transplantation;Bone Marrow Transplantation;Brain;cell type;Cells;Cellular Metabolic Process;Cessation of life;Childhood;Complex;Data;Defect;Disease;early childhood;effective therapy;Energy Metabolism;Engraftment;enzyme activity;extracellular vesicles;Genetic Polymorphism;Hematopoietic;hematopoietic engraftment;Homeostasis;Immune;improved;In Vitro;in vivo;Infant Mortality;Inflammation;Inherited;innovation;Intervention;Laboratories;Leigh Disease;life span;Macrophage;Mediating;Metabolic;Metabolism;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;mitochondrial metabolism;Modeling;Morbidity - disease rate;mortality;Movement Disorders;Mus;Nanotubes;Natural regeneration;Nerve Degeneration;Nervous System Physiology;Neuroglia;Neurologic;Neurologic Symptoms;Neurons;novel;novel therapeutic intervention;novel therapeutics;Organ;Pathway interactions;Patients;pharmacologic;postnatal;Process;PTPRC gene;Reporter;Reporting;Research;respiratory;self-renewal;Severities;Severity of illness;Source;targeted treatment;Techniques;Technology;Therapeutic;Tissues;Transplantation;Work

PROJECT_TITLE: Harnessing mitochondria transfer pathways to ameliorate Leigh Syndrome-like disease

STUDY_SECTION: TAG

STUDY_SECTION_NAME: Therapeutic Approaches to Genetic Diseases Study Section[TAG]


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;Cerebrovascular;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Lung;Neurodegenerative;Neurosciences;Patient Safety;Pneumonia;Pneumonia and Influenza;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: MOBILE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF SOUTH ALABAMA

ORG_STATE: AL

PHR: PROJECT NARRATIVE Some pneumonia survivors, including those with post-intensive care unit syndrome, suffer from cognitive deficits, reducing their quality of life and inflicting healthcare and financial hardships. Strikingly, pneumonia-associated microorganisms (e.g., P. aeruginosa) trigger lung endothelial production and release of several cytotoxic amyloids (e.g., tau and Aβ) that are key pathological hallmarks of dementia. Whether pneumonia-elicited lung endothelial cytotoxic tau variants initiate blood-brain barrier breakdown to induce neurovascular unit dysfunction (e.g., pericyte injury, gliosis, and impaired hemodynamics), and whether APOE-ε4-induced neurovascular unit dysfunction exacerbates the negative impact of lung endothelial tau on the brain remains to be determined and are the focus of this study.

PI_NAMEs: NELSON, AMY R (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: 2019-nCoV;Address;Amyloid;Amyloid beta-Protein;Antibodies;apolipoprotein E-4;Apolipoproteins;Autopsy;Bacterial Pneumonia;Biological Assay;Biological Markers;Biology;Blood;Blood - brain barrier anatomy;Blood Circulation;Brain;brain dysfunction;cerebral hemodynamics;Cerebrovascular Circulation;Cerebrovascular system;Clinical;Clinical Research;Cognitive deficits;cytokine;cytotoxic;Data;Dementia;Dendritic Spines;density;Dependovirus;Endothelial Cells;Endothelium;Event;experience;Experimental Models;experimental study;Financial Hardship;Functional disorder;genetic risk factor;Genotype;Gliosis;health disparity;Healthcare;hemodynamics;Hospital Mortality;human tissue;imaging study;Impaired cognition;Impairment;In Vitro;Incidence;Infection;Injury;innovation;Intensive Care Units;intravital microscopy;Knowledge;Learning;Length of Stay;Link;Lung;Maintenance;Memory;Methodology;microorganism;mild cognitive impairment;Mus;Neurologic Deficit;Neurons;neurovascular;neurovascular injury;neurovascular unit;normal aging;Nosocomial pneumonia;novel;Operative Surgical Procedures;Organ;pathogen;Pathologic;Pathology;Patients;Pericytes;Peripheral;Phosphorylation;Plasma;Platelet-Derived Growth Factor Receptor;Pneumonia;Postoperative Period;pre-clinical;prevent;Production;Protein Isoforms;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Quality of life;Regulation;Resolution;response;Sampling;sarkosyl;Sepsis;Severities;Speed;Survivors;Syndrome;tau aggregation;tau Proteins;Tauopathies;Testing;two-photon;Variant;Viral Pneumonia;Work

PROJECT_TITLE: Nosocomial pneumonia impairs the cerebrovasculature

STUDY_SECTION: SAT

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


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Genetics;Human Genome;Prevention

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: Genetic differences between people and populations can impact the risk of adverse effects from environmental exposures. Improved understanding of the relationship between genetic susceptibility and the environment is critical to protecting public health. Current approaches have had limited success in identifying human health relevant interactions. We propose a fundamentally different approach to functional assess commonly variant human genes for their role in specific environmental exposures which could enable more effective human risk assessment.

PI_NAMEs: VULPE, CHRISTOPHER D (contact)

PROGRAM_OFFICER_NAME: DUNCAN, CHRISTOPHER GENTRY

PROJECT_TERMS: 3-Dimensional;Adverse effects;adverse outcome;Affect;Biological;biological adaptation to stress;Candidate Disease Gene;candidate identification;Cell Differentiation process;Cell Line;Cell model;Cell Proliferation;Cells;Chemicals;Clustered Regularly Interspaced Short Palindromic Repeats;comparative;Complex;Coupled;CRISPR library;CRISPR screen;Databases;Dose;drug candidate;Environment;Environmental Exposure;environmental stressor;Evaluation;Exposure to;Frequencies;gene environment interaction;Gene Expression;Genes;Genetic;genetic association;Genetic Predisposition to Disease;Genetic Transcription;genetic variant;Genetic Variation;Health;Human;Human Genetics;improved;Individual;Libraries;loss of function;loss of function mutation;Measures;Metabolic;Mutation;Organoids;Outcome;Pathway interactions;Persons;Phenotype;Physiological;Population;Predisposition;Preventive;Public Health;Reporter;resilience;Resources;response;Risk;Risk Assessment;risk mitigation;Role;single-cell RNA sequencing;Stress;stressor;success;Therapeutic;tool;toxicant;Toxicant exposure;Toxicogenomics;Toxicology;Toxin;Validation;Variant;vector

PROJECT_TITLE: CRISPR screens of population relevant genes governing toxicant resilience


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Fentanyl Misuse and Addiction;Genetics;Neurosciences;Opioid Misuse and Addiction;Opioids;Pain Research;Substance Misuse

ORG_CITY: Newark

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Mu opioids such morphine and fentanyl are potent in relieving pain, but they produce many side-effects such as tolerance and addiction, leading to the worldwide opioid epidemic and climbing opioid overdose death. The proposed studies aim to investigate novel molecular mechanisms and functions of mu opioid tolerance and reward that are mediated through fat mass and obesity-associated protein (FTO), a mRNA demethylase.

PI_NAMEs: JAFFREY, SAMIE R;PAN, YING-XIAN  (contact)

PROGRAM_OFFICER_NAME: WU, DA-YU

PROJECT_TERMS: 3-Dimensional;Absence of pain sensation;addiction;Address;alpha ketoglutarate;Alternative Splicing;Attenuated;attenuation;AVIL gene;candidate identification;Central Nervous System;Complex;conditioned place preference;Data;demethylation;Development;Dioxygenases;Dorsal;Drug Addiction;drug reward;Epigenetic Process;Exhibits;fat mass and obesity-associated protein;Fentanyl;Ganglia;Gene Expression;Heterozygote;in vivo;inducible Cre;inhibitor;insight;Intravenous;Knockout Mice;Link;LoxP-flanked allele;Mainstreaming;Maps;Measures;Mediating;Messenger RNA;Methyltransferase;Microinjections;Modeling;Modification;Molecular;Morphine;morphine tolerance;mouse model;mRNA Stability;Mus;Neurons;neuropsychiatric disorder;novel;novel strategies;Nucleotides;Nucleus Accumbens;opiate tolerance;Opioid;Opioid Analgesics;opioid epidemic;opioid mortality;opioid use disorder;Pain management;pain relief;Pathway interactions;Peripheral Nervous System;Play;preservation;Protein Inhibition;Rewards;Ribosomal RNA;ribosome profiling;RNA methylation;RNA Splicing;Role;Self Administration;side effect;Signal Pathway;Site;Spinal Ganglia;System;Tamoxifen;Testing;Therapeutic;transcriptome;transcriptome sequencing;Translations

PROJECT_TITLE: Molecular mechanisms and functions underlying the role of Fto in mu opioid actions

STUDY_SECTION: MCNP

STUDY_SECTION_NAME:
Molecular and Cellular Neuropharmacology Study Section
[MCNP]


ADMINISTERING_IC: HL

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

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

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Narrative Vaccinations are one of the most beneficial and cost-effective public health programs. Unfortunately, many vaccines need repeated boosting to maintain antibody levels to generate long-lived plasma cells, which can survive for a lifetime in the body. We are focused on understanding how to enhance the longevity of the cells to improve immune function.

PI_NAMEs: FOOKSMAN, DAVID R (contact)

PROGRAM_OFFICER_NAME: AGRAWAL, NITIN

PROJECT_TERMS: Adhesions;Affinity;Alleles;anthrax toxin;anti-CD20;Antibodies;Antibody Response;Antibody titer measurement;Antigens;bone;Bone Marrow;booster vaccine;Cell Lineage;Cell Maturation;Cell Survival;Cells;cost effective;CXCR4 gene;cytokine;Docking;Enterobacteria phage P1 Cre recombinase;Flow Cytometry;Genus Mentha;Grant;Health;Hematopoietic;Homing;Hour;Human;Image;immune function;Immunization;Immunoglobulin-Secreting Cells;Immunologic Memory;improved;in vivo;Integrin alpha4beta1;Interleukin-6;intravital imaging;Intrinsic factor;Link;Locales;Longevity;Malignant - descriptor;Measles;Measles virus;Mediating;Membrane Proteins;Memory;Memory B-Lymphocyte;Monitor;Motility;Movement;Mus;Names;older adult;Organ;Paper;pathogen;Pathway interactions;Pattern;photoactivation;Plasma Cells;programs;prophylactic;Proteins;Public Health;Publishing;radioresistant;receptor;Reporter;Reporting;Residencies;response;Reticular Cell;Role;screening;Series;Serology;Serum;Signal Transduction;Site;Specific qualifier value;Spleen;Stromal Cell-Derived Factor 1;Structure;Supporting Cell;Surface;Tamoxifen;Testing;Tetanus;Tetanus Toxin;Time;Tissues;transcriptome;transcriptome sequencing;Transgenic Mice;Vaccination;Vaccines

PROJECT_TITLE: CD138 Regulates Competition of Antibody Secreting Cells for Survival

STUDY_SECTION: CMIB

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Cardiovascular;Clinical Research;Genetics;Heart Disease;Human Genome;Precision Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CHICAGO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: NARRATIVE By combining cardiotoxicity response eQTLs with patient data, we aim to develop a classifier that can predict who is at increased risk of drug-induced cardiovascular decline, which would be a major improvement in patient care.

PI_NAMEs: GILAD, YOAV  (contact)

PROGRAM_OFFICER_NAME: SHANBHAG, SUJATA MADHUKAR

PROJECT_TERMS: Acute;Affect;Anthracycline;anti-cancer treatment;Antineoplastic Agents;Arrhythmia;bevacizumab;biomarker identification;Blood Vessels;Cancer Patient;Cancer Survivor;cancer therapy;Candidate Disease Gene;candidate identification;Cardiac;Cardiac Myocytes;Cardiotoxicity;cardiovascular risk factor;Cardiovascular system;Cell Culture Techniques;cell type;Cells;Cessation of life;Classification;Clinical;clinical phenotype;cohort;Complex;Data;Data Set;differentiation in vitro;differentiation protocol;Disease;Doxorubicin;Endocardium;Endothelial Cells;Epicardium;Fibroblasts;Fluorouracil;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Transcription;genetic variant;Genotype;Goals;health record;Heart;Heart failure;Heritability;human induced pluripotent stem cells;Hypertension;improved;In Vitro;Individual;induced pluripotent stem cell;induced pluripotent stem cell derived cardiomyocytes;inter-individual variation;Long-Term Effects;machine learning classifier;Malignant Neoplasms;Measures;Mediating;Medical Records;molecular phenotype;Morbidity - disease rate;mortality;novel;Patient Care;Patients;Pharmaceutical Preparations;Pharmacogenomics;Pharmacotherapy;polygenic risk score;Population Heterogeneity;power analysis;Predisposition;premature;Quantitative Trait Loci;Research;Resistance;response;Rest;Risk;Sample Size;Sampling;single cell sequencing;single-cell RNA sequencing;System;Testing;Therapeutic;Tissues;Toxic effect;trait;transcriptomics;treatment response;Treatment-Related Cancer;Variant;Vascular Endothelial Cell;Vascular System;whole genome;Work

PROJECT_TITLE: Using guided differentiation to predict cancer treatment related cardiotoxicity

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Digestive Diseases;Genetics;Inflammatory Bowel Disease;Microbiome

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE The Inflammatory Bowel Diseases (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), are diseases of the gastrointestinal tract that result from abnormal immune response to luminal antigens in genetically-susceptible individuals. IBD represents a disease of major interest, with more than 3 million American afflicted with this chronic inflammatory disorder. The proposed studies are designed to identify and harness information from novel inflammation-related metabolic pathways that promote tissue healing through interactions with metabolites derived from bacteria found in the lumen (i.e. the “microbiota”). Such studies should provide new avenues into our understanding of why inflammatory diseases develop, and in particular, how innate immune responses contribute to inflammatory resolution.

PI_NAMEs: COLGAN, SEAN P (contact)

PROJECT_TERMS: Acute;Address;American;analog;Antigens;Bacteria;Bioconductor;Biological Assay;Butyrates;Cell Line;Cell Physiology;Chronic;cohort;Colon;commensal bacteria;Crohn's disease;design;Digestive System Disorders;Disease;disease model;Dissection;dysbiosis;Epithelial Cells;Epithelium;Etiology;experimental study;Formulation;gain of function;Gastrointestinal Diseases;Gene Expression;Genes;Genetic;genetic signature;Genetic Transcription;Germ-Free;Goals;gut inflammation;gut microbiota;healing;Health;Histone Deacetylase;host-microbe interactions;Hypoxia;Hypoxia Inducible Factor;ileum;Immune response;in vivo;in vivo Model;Incidence;Individual;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inhibitor;Innate Immune Response;insight;interest;Intestinal Diseases;intestinal epithelium;intestinal homeostasis;Intestinal Mucosa;Intestines;Libraries;loss of function;Maps;Metabolic;Metabolic Pathway;Metabolism;Microbe;microbial;microbial community;microbial host;microbiota;microbiota metabolites;mimetics;mimicry;Modality;Modeling;Modification;Molecular;Molecular Mimicry;Molecular Target;mouse model;Mucositis;Mucous Membrane;Mus;novel;novel therapeutics;Oxygen;Pathway Analysis;Pathway interactions;pharmacologic;Physiological;Population;Positioning Attribute;Predisposition;Procollagen-Proline Dioxygenase;Regulation;Resolution;response;Role;Signal Transduction;single-cell RNA sequencing;Subcellular Anatomy;Submucosa;Testing;Tissues;TNF gene;tool;transcription factor;Transgenic Mice;Ulcerative Colitis;Volatile Fatty Acids;Western World;Work;wound healing

PROJECT_TITLE: Metabolic Regulation of Inflammation by Microbial SCFA

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Brain Disorders;Clinical Research;Multiple Sclerosis;Neurodegenerative;Neurosciences;Prevention

ORG_DEPT: NEUROLOGY

PHR: Project Narrative A major clue to the nature of disease in multiple sclerosis is suggested by the increased amounts of antibody in the brain and cerebrospinal fluid of MS patients. We have developed unique strategies to produce large amounts of this cerebrospinal fluid antibody in tissue culture cells and have demonstrated that antibody binds to myelin proteolipid membrane complex and produces demyelination, oligodendrocyte cell death and tissue damage when injected into the brain of mice. The goals of this proposal are to (1) molecularly dissect the specific antigenic targets identified by complex MS myelin-specific antibodies, (2) determine the prevalence of various epitope-specific CSF and serum PLP1 Abs in MS patients and correlate their presence and titer with disease severity, and (3) delineate the role of pathogenic PLP1 Abs in MS lesion pathology.

PI_NAMEs: BENNETT, JEFFREY L (contact);OWENS, GREGORY PARKS

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: accurate diagnosis;Address;Adult;Antibodies;Antibody Formation;Antigen Presentation;Antigen Targeting;Antigens;Astrocytes;Autopsy;B-Lymphocytes;Binding;Binding Proteins;biobank;Biological Assay;Biopsy Specimen;Brain;Cd68;Cell Death;Cells;Central Nervous System;central nervous system demyelinating disorder;Central Nervous System Diseases;central nervous system injury;Cerebrospinal Fluid;Childhood;Cholesterol;Clinical;Clinical Data;Clone Cells;Complement;Complement Membrane Attack Complex;Complement-Dependent Cytotoxicity;Complex;cytokine;Data;demographics;Demyelinations;Deposition;Diagnosis;diagnostic biomarker;diagnostic criteria;disability;Disease;disorder control;Documentation;Early treatment;Enzyme-Linked Immunosorbent Assay;Epitopes;Etiology;Functional disorder;Galactosylceramides;Gene Targeting;Glycolipids;Goals;Histopathology;Human;IgG1;Immune response;Immunoassay;Immunochemistry;Immunoglobulin G;Immunologics;Immunoprecipitation;improved;in vivo;in vivo Model;Individual;Infiltration;Inflammatory;Iron;Knockout Mice;Lesion;Link;Magnetic Resonance Imaging;Measurable;Mediating;Membrane;Membrane Lipids;Membrane Proteins;Microinjections;Modeling;Molecular;Molecular Conformation;Multiple Sclerosis;Multiple Sclerosis Lesions;multiple sclerosis patient;Mus;Myelin;Myelin Proteins;Myelin Proteolipid Protein;Nature;Nervous System control;Nervous System Disorder;Neurologic;Neurological disability;Neurons;novel;novel marker;Oligoclonal Bands;Oligoclonal IgG;Oligodendroglia;pathogen;Pathogenesis;pathogenic autoantibodies;Pathogenicity;Pathology;Patient Care;Patients;Phagocytes;Phase;Plasmablast;Play;Prevalence;Process;Prognosis;Prognostic Marker;protein complex;Proteins;Proteolipids;Protocols documentation;rapid diagnosis;Recombinant Antibody;Recombinants;Recording of previous events;Relapse;remyelination;repaired;response;Role;Sampling;Sensitivity and Specificity;Serum;Severity of illness;Slice;Solid;specific biomarkers;Specificity;Specimen;Sulfoglycosphingolipids;Syndrome;T-Lymphocyte;Testing;Therapeutic;therapeutic biomarker;Time;time use;tissue/cell culture;Tissues;Transfection;Transgenic Organisms;treatment response;white matter

PROJECT_TITLE: Contribution of antibodies targeting PLP1-anchored membrane domains to multiple sclerosis pathogenesis

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_NAME: DANA-FARBER CANCER INST

PHR: PROJECT NARRATIVE Cancer genomes are shaped by mutation and chromosome rearrangement. Understanding mutational processes driving these alterations advances our understanding of how cancer develops and has potential to lead to new cancer therapies. Building on methods unique to our laboratory, we propose to elucidate the mechanisms of catastrophic mutational processes that drive very rapid evolution of cancer genomes.

PI_NAMEs: PELLMAN, DAVID S (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Address;Automobile Driving;cancer genome;cancer initiation;cancer therapy;Cell division;Cell Nucleus;Cells;Chromatin;Chromosomal Instability;Chromosomes;chromothripsis;Cytoplasm;Daughter;daughter cell;DNA;DNA biosynthesis;DNA Damage;DNA Fragmentation;Event;Evolution;Generations;Genetic Transcription;Genome;Goals;Heritability;Human;Interphase;Laboratories;Ligation;Link;Malignant Neoplasms;Methods;micronucleus;Mitosis;Mitotic;Mutation;Nuclear;Nuclear Envelope;p53-binding protein 1;Pathogenesis;Positioning Attribute;Process;Research;response;segregation;Shapes;single cell genomics;Spontaneous Rupture;Structure;Technology;Transcription Alteration;tumor;Work

PROJECT_TITLE: Mechanisms Driving the Rapid Evolution of Cancer Genomes

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-E (M1)]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

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

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROJECT NARRATIVE This project will develop scalable computational methods for estimating probabilistic model parameters and in- ferring genealogical information across different timescales, which will significantly facilitate the analysis and interpretation of human genome variation as well as single-cell genomics data. The user-friendly software tools stemming from this research will be broadly applicable to scale up inference under many settings, thereby en- abling the biomedical research community to better harness massive genomic data to improve human health. In particular, the methods developed in this project will be applied to study the biology of metastasis in cancer and antibody maturation in the immune system.

PI_NAMEs: HOLMES, IAN H;NIELSEN, RASMUS ;SONG, YUN S (contact)

PROGRAM_OFFICER_NAME: GAO, JEAN XUEJING

PROJECT_TERMS: Address;Affinity;Antibodies;Attention;B-Lymphocytes;Biological;Biology;Biomedical Research;CCL21 gene;Cell Lineage;Cells;Clinical;Collection;Communities;Complex;Computer software;computerized tools;Computing Methodologies;CRISPR/Cas technology;Data;Data Compression;Data Set;Evolution;Experimental Designs;experimental study;fitness;Foundations;G-Protein-Coupled Receptors;Genetic;Genetic Recombination;Genetic Variation;Genome;genome editing;genome wide association study;genome-wide;genomic data;Genomics;Genotype;Goals;Graph;Health;Homologous Protein;Human;human data;Human Genetics;Human Genome;Immune system;improved;in vivo;innovation;insertion/deletion mutation;Joints;large datasets;Length;Malignant Neoplasms;Maps;Maximum Likelihood Estimate;Meiotic Recombination;Membrane Proteins;Methods;Modeling;Modernization;Molecular Evolution;molecular modeling;Natural Selections;Neoplasm Metastasis;next generation;novel;open source;Organism;Parameter Estimation;Phase;Phylogenetic Analysis;Population;Positioning Attribute;Process;protein structure;Proteins;Recording of previous events;Research;Research Personnel;Sampling;scalable algorithms;scale up;single cell genomics;Site;Software Tools;solute;Source;Speed;Statistical Data Interpretation;Statistical Methods;Statistical Models;STEM research;Structural Models;Structure;Structure of germinal center of lymph node;Techniques;Technology;Testing;theories;Time;tool;Trees;user friendly software;user-friendly;Variant;Work

PROJECT_TITLE: Scalable Computational Methods for Genealogical Inference: from species level to single cells

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Childhood Obesity;Clinical Research;Mental Health;Neurosciences;Obesity;Pediatric;Prevention

ORG_CITY: NEW YORK

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Narrative Risk-taking is a hallmark characteristic of adolescence; while risk-taking is an essential component of evolutionary survival and experiential learning, maladaptive or irrational risk-taking in adolescence is associated with significant morbidity and mortality. During this critical life stage, profound brain remodeling and behavioral development may be influenced by early-life environmental exposures, affecting developmental trajectories related to risk-taking, yet such research is challenging, time-intensive, and costly to perform. We will leverage an ongoing cohort study to assess the impact of early-life metal exposures on developmental trajectories of adolescent risk-taking behaviors spanning more than 20 years, critical research needed to understand risk-taking behaviors and inform effective and timely interventions to promote optimal adolescent development.

PI_NAMEs: HORTON, MEGAN K (contact)

PROGRAM_OFFICER_NAME: GRAY, KIMBERLY A

PROJECT_TERMS: Acceleration;Active Learning;Address;Adolescence;Adolescent;adolescent brain development;Adolescent Development;adolescent health;Adolescent Risk Behavior;Adult;Affect;Age;aged;alcohol and other drug;Area;Attention;Automobile Driving;Behavior;Behavior Disorders;Behavioral;behavioral outcome;behavioral phenotyping;Biological Markers;Brain;Brain region;brain remodeling;brain reward regions;Categories;Characteristics;Child;Childhood;cognitive control;cohort;Cohort Studies;conduct problem;cost;cost effective;Data;design;Development;dietary;Dropout;Drug usage;early life exposure;Economics;Education;Emotional;Enrollment;Environment;Environmental Exposure;Exposure to;follow up assessment;follow-up;Foundations;frontal lobe;Future;Grant;Growth;Health;Human Development;improved;Impulsivity;Individual;innovation;Intervention;Knowledge;Lead;Life;Life Cycle Stages;Link;Literature;Longitudinal cohort;longitudinal design;Longitudinal Studies;Magnetic Resonance Imaging;Manganese;Measures;Mediation;Mediator;Metal exposure;Metals;Modeling;Morbidity - disease rate;mortality;Motivation;MRI Scans;multimodality;neural;neural circuit;neurobehavioral;neuroprotection;Neuropsychology;neurotoxic;novel;Obesity;Participant;Patient Self-Report;Perinatal;Perinatal Exposure;Phenotype;phenotypic data;postnatal;preadolescence;Pregnancy;Pregnancy Outcome;prenatal;Preventive measure;prospective;public health intervention;Research;Rewards;Risk;Risk Assessment;Risk Behaviors;Risk Taking;Sample Size;Schools;social stressor;Statistical Methods;Structure;Substance abuse problem;Time;tool;Tooth structure;Toxic Environmental Substances;transition to adulthood;Violence;Visit;Zinc

PROJECT_TITLE: Longitudinal study of metal mixtures and the developmental origins of adolescent risk-taking

STUDY_SECTION: LHB

STUDY_SECTION_NAME: Lifestyle and Health Behaviors Study Section[LHB]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: PISCATAWAY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

PHR: PROJECT NARRATIVE: Our proposed research focuses on the return of internalized macromolecules to the cell surface from endosomes (endocytic recycling), a basic cell biological processes that is of fundamental importance to many areas of biomedicine. Endocytic recycling is a key control point in the insulin-stimulated movement of glucose transporters (Glut4) from endosomes to the plasma membrane, a process that goes awry in type II diabetes.

PI_NAMEs: GRANT, BARTH DEMIAN (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Actins;Actomyosin;Acute;Adult;Animal Model;Animals;Area;Attention;Autophagocytosis;Binding;Biogenesis;Biological Models;Biological Process;Biosensor;Caenorhabditis elegans;Cell division;Cell membrane;Cell Nucleus;Cell Polarity;Cell surface;Cells;Cues;Cytokinesis;Cytoskeleton;Development;Elements;Embryonic Development;Endocytosis;endosome membrane;Endosomes;Epithelium;Event;extracellular;F-Actin;Feedback;Fibroblasts;Frequencies;Funding;Genetic Transcription;Glucose Transporter;Grant;Growth Factor;Guanosine Triphosphate Phosphohydrolases;Image;imaging modality;Individual;insight;Insulin;Interphase Cell;Intestines;Laboratories;Link;Lipids;Lysosomes;macromolecule;Mammalian Cell;Mammals;Measures;Membrane;Metabolic;migration;Modeling;Molecular;Monomeric GTP-Binding Proteins;Movement;Mus;mutant;Myosin ATPase;Myosin Type II;Natural regeneration;Neurons;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;non-muscle myosin;novel;Nutrient;Organelles;Organism;Parkinsonian Disorders;Pathway interactions;Phenotype;Phylogenetic Analysis;Physiologic pulse;Physiological;Play;polymerization;Polymers;Population;Positioning Attribute;predictive modeling;Process;Protein Isoforms;Proteins;rab GTP-Binding Proteins;Recycling;Regulation;Reporting;Research;response;Role;Signal Transduction;Site;Sorting;Structure;Synaptic plasticity;System;Testing;trafficking;transcription factor;Transmembrane Transport;Tube;Tubular formation;uptake;Vesicle;vesicular release;Work

PROJECT_TITLE: Molecular regulation of endosome fission during endocytic recycling

STUDY_SECTION_NAME: Cell Structure and Function 1 Study Section[CSF1]


NIH_SPENDING_CATS: Bioengineering;Osteoporosis

ORG_CITY: SYRACUSE

ORG_NAME: SYRACUSE UNIVERSITY

PHR: Narrative While bone tissue dynamically adapts to mechanical stimuli to maintain its strength, disrupted signaling between bone cells is a major factor in the initiation and progression of many skeletal diseases that are difficult and costly to treat. The proposed work will use a novel model system to expand our understanding of how mechanical stimuli determine the adaptive response of bone tissue.

PI_NAMEs: SOMAN, PRANAV  (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: 3-Dimensional;Ablation;Acceleration;Behavior;Biological Models;Biomedical Engineering;bone;bone cell;Bone Diseases;Bone remodeling;Bone Resorption;Bone Tissue;Calcium Signaling;Cell Physiology;cell type;Cells;Cellular biology;Coculture Techniques;Coin;Collagen;cost;cytokine;Degenerative polyarthritis;Development;Devices;Drug Evaluation;Effector Cell;empowerment;experimental study;fluid flow;Frequencies;functional outcomes;Future;Gene Expression;Goals;Hour;In Vitro;in vitro Model;in vivo Model;Individual;injured;irradiation;Lasers;Link;Liquid substance;mechanical stimulus;Mechanics;mechanotransduction;Methods;Microfluidic Microchips;Modeling;Morphology;novel;Orthopedic Surgery;Osteoblasts;Osteoclasts;Osteocytes;Osteogenesis;Osteoporosis;Outcome;Paracrine Communication;Pathway interactions;Periodicity;Physiologic pulse;Production;Property;Protocols documentation;Publishing;Recovery;Reproducibility;Research;response;Role;self assembly;Signal Transduction;skeletal;skeletal disorder;spatiotemporal;Statistical Data Interpretation;Stimulus;Testing;Time;Translating;transmission process;Visualization;Work

PROJECT_TITLE: Role of Ca2+ Signaling by 3D Osteocyte Networks in Mechanoadaptive Response of the Bone Multicellular Unit

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


NIH_SPENDING_CATS: Hematology;Kidney Disease

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Despite decades of research into the pathophysiology of AKI and improvements in supportive care, acute kidney injury (AKI) remains a major clinical problem with high mortality rates. RBC trapping is a hallmark of injury in ischemic AKI. A better understanding of the mechanisms driving kidney injury from RBC trapping will improve treatment options for both men and women and reduce the overall health burden in the United States.

PI_NAMEs: O'CONNOR, PAUL MICHAEL (contact)

PROGRAM_OFFICER_NAME: SADUSKY, ANNA BURKART

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Address;Animal Model;Automobile Driving;Back;basolateral membrane;Blood;Blood capillaries;Blood Vessels;Cardiovascular system;cell injury;Cells;Chronic Kidney Failure;Clinical;Cortical Vein;Cutaneous;Data;Death Rate;Distal;effective therapy;Electron Microscopy;Endocytosis;Endocytosis Inhibition;Epithelium;Erythrocytes;Event;Extravasation;Filtration;fluorescence imaging;Fluorescent Dyes;Functional disorder;glomerular filtration;Goals;Haptoglobins;Health;Heme;Hemoglobin;Hour;Human;Hydrostatic Pressure;Hypotension;improved;in vivo;Injury;Injury to Kidney;Ischemia;Kidney;kidney cortex;Knowledge;Label;Maintenance;Measurement;Mediating;Membrane Potentials;men;mitochondrial dysfunction;mitochondrial membrane;mortality;Nephrons;novel strategies;Oliguria;Output;Pathogenesis;Pathologic;patient prognosis;Patients;photoacoustic imaging;Plasma;Predisposition;pressure;Process;Production;Publishing;Rattus;Recommendation;Recovery;Regional Perfusion;Renal Blood Flow;Renal function;renal ischemia;Reperfusion Injury;Reperfusion Therapy;Research;Risk;Role;Shock;Supportive care;Testing;Text;Time;Toxic effect;Transfusion;Tubular formation;United States;uptake;Urine;Veins;Woman

PROJECT_TITLE: Red blood cell trapping mediates toxic kidney injury following ischemia

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


NIH_SPENDING_CATS: Cancer;Clinical Research;Digestive Diseases;Liver Disease;Neuroblastoma;Neurosciences;Pediatric;Pediatric Cancer;Prevention;Rare Diseases;Skin Cancer

ORG_CITY: LOS ANGELES

ORG_NAME: CHILDREN'S HOSPITAL OF LOS ANGELES

PHR: NARRATIVE Most patients with cancer succumb to their disease because cancer cells can disseminate to various organs, a complex process called metastasis, which is hard to detect early on, to prevent and to treat. This grant proposal focuses on developing a mechanistic understanding of one of the earliest steps in metastasis, the formation of the pre-metastatic niche, and on testing the hypothesis that small vesicles released by tumor cells and taken by sentinel immune cells in organs prone to metastasis trigger an inflammatory reaction that favors organ colonization by metastatic tumor cells. The long-term goal is to identify targets within the metastatic process to intervene when it is in early development.

PI_NAMEs: DECLERCK, YVES A (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: Aftercare;antagonist;Applications Grants;Bone Marrow;Bone Marrow Cells;cancer cell;Cancer Patient;Cause of Death;Cell Communication;Cells;chemokine;chemotherapy;Child;Collection;Complex;cytokine;Cytometry;Data;design;Development;Disease;Early Diagnosis;Event;Evolution;experimental study;Extracellular Matrix;extracellular vesicles;Family;gain of function;Genetic;Genetic Transcription;Goals;Grant;Human;IL18 gene;Image;Immune;immune activation;Immunocompetent;Immunodeficient Mouse;Immunosuppression;Implant;In Vitro;in vivo;Inflammasome;Inflammatory;Interleukin-1 beta;Intervention;Kinetics;Label;Laboratories;Liver;loss of function;Macrophage;Malignant Neoplasms;marenostrin;Melanoma;Melanoma Cell;metastasis prevention;Metastatic Neoplasm to the Liver;metastatic process;Methods;Modeling;Molecular;Morphologic artifacts;mouse model;Mus;Myeloid Cells;Myeloid-derived suppressor cells;Neoplasm Metastasis;neoplastic cell;Neuroblastoma;neuroblastoma cell;Organ;Pathway interactions;Patients;Pattern;pharmacologic;Population;prevent;Prevention;Process;Production;prospective;protein expression;Proteins;Publishing;Reaction;receptor;recruit;Reporting;Role;Sampling;Sentinel;Signal Transduction;single cell analysis;spatiotemporal;Stromal Cells;Testing;Therapeutic Agents;Therapeutic Intervention;therapy development;Time;Tissues;Transplantation;Tumor-Derived;tumor-immune system interactions;vesicular release;Work

PROJECT_TITLE: Tumor-derived extracellular vesicles in the pre-metastatic niche.

STUDY_SECTION: THI

STUDY_SECTION_NAME: Tumor Host Interactions Study Section[THI]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Digestive Diseases;Pancreatic Cancer;Prevention;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Project Narrative Pancreatic cancer is one of the deadliest forms of cancers. It is estimated that 8 million Americans have pancreatic cystic lesion, the only readily identifiable precursor of pancreatic cancer. The purpose of this program is to develop the in vivo optical technique that can be used during minimally invasive endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) procedures, providing accurate diagnosis of pancreatic cystic lesions and assessment of their malignant potential, needed to improve life-saving decisions and help to deal with the large prevalence of cysts being discovered recently with MRI/CT imaging.

PI_NAMEs: PERELMAN, LEV T (contact)

PROGRAM_OFFICER_NAME: ANDERSON, AFROUZ AZARI

PROJECT_TERMS: accurate diagnosis;accurate diagnostics;Address;Adopted;American;Articulation;aspirate;Award;Benign;bile duct;biological development;Biomedical Engineering;biomedical imaging;Biopsy;Cancer Detection;Cancer Etiology;Cancerous;Cells;Cessation of life;Characteristics;Chemicals;Clinical;clinical application;Clinical Research;Collection;Curative Surgery;Cyst;Cyst Fluid;Cystic Lesion;Data;Data Collection;Death Rate;Development;Diagnosis;Diagnostic;diagnostic algorithm;diagnostic platform;Diagnostic Procedure;diagnostic strategy;diagnostic technologies;Disease;Doctor of Philosophy;Double-Blind Method;Duct (organ) structure;Endoscopic Ultrasonography;Endoscopy;Ensure;Epithelium;Evaluation;Excision;Exhibits;Feedback;Fiber;Fine needle aspiration biopsy;Foundations;Future;Gastroenterology;Gastrointestinal tract structure;GNAS gene;Goals;Grant;Growth;High grade dysplasia;Histologic;image translation;Imaging Device;Imaging Techniques;improved;in vivo;Incidental Findings;Institutional Review Boards;instrument;instrumentation;International;KRAS2 gene;Legal patent;Lesion;Life;Light;Light-Scattering Spectroscopy;Liquid substance;Magnetic Resonance Imaging;Malignant - descriptor;Malignant Breast Neoplasm;Malignant neoplasm of pancreas;Malignant Neoplasms;man;Maps;Measurement;medical schools;meetings;minimally invasive;Modeling;Molecular;Monitor;Morbidity - disease rate;mortality;Mutation;Nature;Needles;Noise;non-invasive imaging;novel;novel diagnostics;operation;Operative Surgical Procedures;Optics;Organ;Outcome;Pancreas;Pancreatectomy;Pancreatic Cyst;Pancreatic cystic neoplasia;Paper;Pathology;Patients;performance tests;photonics;Positioning Attribute;Predictive Value;premalignant;Prevalence;Procedures;Prognosis;programs;Property;Publishing;Research Peer Review;risk prediction model;Robotics;Sampling;Scanning;screening;Screening for cancer;Side;Signal Transduction;Site;Specificity;spectroscopic data;standard of care;statistics;Surface;symposium;System;Techniques;Technology;Testing;Time;tissue phantom;Tissues;Training;Translating;United States;Validation;X-Ray Computed Tomography

PROJECT_TITLE: Endoscopic Fine-Needle Light Scattering Spectroscopy for Pancreatic Cyst Diagnosis and Evaluation of Malignant Potential

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


NIH_SPENDING_CATS: Autoimmune Disease;Bioengineering;Biotechnology;Digestive Diseases;Gene Therapy;Genetics;Immunotherapy;Inflammatory Bowel Disease

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Our goal is to define and characterize a novel cellular therapeutic strategy to treat autoimmune diseases. Our approach involves the development of chimeric antigen receptor-engineered mesenchymal stromal cells (CAR- MSCs) for enhanced tissue-targeting and immunosuppressive effects. Our team combines cross disciplinary expertise in immune cell engineering, CAR development, inflammatory bowel disease, and genetics.

PI_NAMEs: KENDERIAN, SAAD J. (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Allogenic;antigen binding;Antigens;Autoimmune Diseases;autoimmune inflammatory bowel disease;Autoimmunity;Binding;biobank;canine model;Canis familiaris;CD28 gene;Cell Communication;Cell Therapy;Cells;cellular engineering;chemokine;chimeric antigen receptor;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Colitis;Colon;cross reactivity;CXCR4 gene;cytokine;Data;design;Development;Disease;E-Cadherin;Engineering;Enhancers;Epithelium;Exhibits;experimental study;Gene Expression Profile;Generations;Genetic;Genetic Transcription;Goals;graft vs host disease;Homing;Immune;Immunocompetent;Immunophenotyping;Immunosuppression;improved;In Vitro;in vivo;in vivo Model;Individual;Inflammation;Inflammatory Bowel Diseases;Integrins;interest;Interferon Type II;Interferons;Knock-out;Lentivirus;Ligands;mesenchymal stromal cell;Modeling;mouse model;multipotent cell;Mus;novel;novel strategies;Pathway interactions;Phase I Clinical Trials;Phenotype;Pre-Clinical Model;prevent;Prevention;Property;receptor;Receptor Signaling;regenerative;Role;Safety;Signal Transduction;Site;stemness;T-Cell Activation;T-Lymphocyte;Testing;Tissues;TLR3 gene;TLR4 gene;tool;trafficking;Treatment Efficacy;Up-Regulation;Vesicular stomatitis Indiana virus;Viral Vector;Work

PROJECT_TITLE: Engineered Mesenchymal Stromal Cells for Enhanced Immunosuppression


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: Princeton

ORG_NAME: PRINCETON UNIVERSITY

PHR: PROJECT NARRATIVE The regulation of RNA in biological systems plays an important role in gene expression programs and defects in this process can lead to human disease. A major mechanism for RNA regulation is through interactions with cellular RNA-binding proteins, and therapeutics that modulate these interactions are currently in development. This proposal seeks to develop a general method for characterizing RNA-protein and RNA-small molecule interactions with application to the development of novel RNA-targeted drugs.

PI_NAMEs: KLEINER, RALPH ELLIOT (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Acceleration;Affect;Amyloidosis;Anti-sense RNA;Antisense Oligonucleotides;base editing;Behavior;Benchmarking;Binding;Bioinformatics;biological systems;Biology;Cells;cellular targeting;Chemicals;Cholesterol;Clinic;Clinical;Code;Coupled;Coupling;crosslink;crosslinking and immunoprecipitation sequencing;Cytoplasm;Cytotoxic agent;Data;Deaminase;Defect;Development;Dimensions;Dimerization;disease-causing mutation;Engineering;Enzymes;Event;G-Quartets;G3BP1 gene;Gene Expression;Gene Expression Regulation;Goals;Heat-Shock Response;human disease;Immunoprecipitation;improved;insight;Knowledge;Label;member;Methods;Modality;Modeling;Molecular;mRNA Translation;Mutation;next generation;novel;novel strategies;novel therapeutics;Nuclear Export;Oligonucleotides;Phase;Physical condensation;Play;Post-Transcriptional Regulation;posttranscriptional;preference;Preparation;Process;programs;Protein Analysis;protein expression;Proteins;Regulation;Resolution;RNA;RNA Binding;RNA Editing;RNA library;RNA Splicing;RNA Stability;RNA-Binding Proteins;RNA-Protein Interaction;RNA-targeting therapy;Role;Sampling;small molecule;small molecule therapeutics;Small RNA;Spinal Muscular Atrophy;Stress;stress granule;System;targeted treatment;Therapeutic;therapeutic target;tool;trafficking;Transcript;transcriptome sequencing;transcriptomic profiling;Translations;Work

PROJECT_TITLE: An RNA editing platform to investigate the dynamic RNA interactome

STUDY_SECTION: CBP

STUDY_SECTION_NAME: Chemical Biology and Probes Study Section[CBP]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Epilepsy;Neurodegenerative;Neurosciences;Pediatric

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project Narrative Epilepsy surgery can result in seizure freedom or a marked reduction in seizures in approximately two-thirds of children with intractable seizures who have been carefully selected, with minimal adverse functional loss. Functional magnetic resonance imaging (fMRI) is an important non-invasive tool that allows the neurosurgeon to precisely map regions of the brain supporting critical functions that should be preserved; however, excessive head motion can lead to mis-identification of these regions, with direct implications for treatment. The proposed project, “Improved 3D EPI for pre-surgical mapping of epilepsy” promises to deliver a highly innovative imaging method capable of producing high-quality functional maps in the presence of uncontrolled head motion by tracking the position of the head and updating the acquisition in real-time.

PI_NAMEs: AFACAN, ONUR  (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: 3-Dimensional;Address;Affect;anti-epileptic agents;Attention deficit hyperactivity disorder;autistic children;blood oxygen level dependent;Brain;Brain region;brain tissue;Cardiac;Child;childhood epilepsy;Clinical;cohort;Compensation;Complex;Data;Drug resistance;Echo-Planar Imaging;effective therapy;Epilepsy;Excision;flexibility;Freedom;functional loss;Functional Magnetic Resonance Imaging;functional MRI scan;Goals;Head;Head Movements;Image;imaging modality;improved;innovation;Language;Lesion;magnetic field;Magnetic Resonance Imaging;Maps;Measurement;Measures;Modality;Modeling;Morphologic artifacts;Motion;Motor Skills;Neurosurgeon;new technology;Noise;novel;Operative Surgical Procedures;patient population;Patients;Pattern;pediatric patients;Physiological;Population;Positioning Attribute;Predisposition;preservation;prevent;prospective;Recommendation;Recording of previous events;recruit;Research;research study;Resolution;Respiration;Scanning;Schedule;Seizures;Signal Transduction;simulation;Slice;spatiotemporal;success;Technology;theories;Time;tool;United States National Institutes of Health;Update;Variant;volunteer

PROJECT_TITLE: Improved 3D EPI for Pre-Surgical Mapping of Epilepsy

STUDY_SECTION: EITN

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


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

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Project Narrative Chronic myeloid leukemia is a devastating blood cancer currently treated with tyrosine kinase inhibitors for a lifetime because most patients relapse upon treatment discontinuation. The main goals of this project are to understand how the kinase DYRK2 abrogates self-renewal and survival of leukemia stem cells and to identify drugs that can stabilize DYRK2 protein and eradicate leukemic stem cells in frontline therapies, which will allow patients to achieve the clinical milestone of cure or treatment-free remission.

PI_NAMEs: LACORAZZA, DANIEL  (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: ABL1 gene;Address;Apoptosis;Biology;c-myc Genes;cancer stem cell;CD34 gene;Cell Line;Cells;checkpoint inhibition;Chronic Myeloid Leukemia;chronic myeloid leukemia cell;Clinical;clinical translation;CRISPR screen;CRISPR/Cas technology;cytotoxic;cytotoxicity;Dependence;Development;Disease;Disease remission;Dose;drug development;effective therapy;Frequencies;Future;Gene Deletion;gene repression;Genes;Genetic;Genetic study;Genetic Transcription;genome-wide;GKLF protein;Goals;Healthcare;Hematologic Neoplasms;Hematology;Hematopoietic Neoplasms;Hematopoietic stem cells;high throughput screening;Human;Imatinib;improved;in vivo monitoring;Knock-in;Knockout Mice;Kruppel-like transcription factors;Laboratories;leukemia;leukemic stem cell;leukemogenesis;Mediating;Medical;Molecular;Molecular Target;mouse model;Mus;novel;Oncoproteins;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacology Study;Phosphorylation;Phosphotransferases;Play;Population;Positioning Attribute;pre-clinical;Pre-Clinical Model;preservation;prevent;Property;Proteins;Proteolysis;Publishing;Recurrent disease;Regulation;relapse patients;Research;Role;self-renewal;small molecule;small molecule libraries;Specificity;stem cell biology;stem cell expansion;stem cell self renewal;success;Survivors;targeted treatment;Testing;Therapeutic;therapeutic target;Toxic effect;TP53 gene;Tyrosine Kinase Inhibitor;Tyrosine Phosphorylation;ubiquitin ligase;Up-Regulation;Vitamin K 3

PROJECT_TITLE: Targeting DYRK2 to eradicate leukemia stem cells in chronic myeloid leukemia.

STUDY_SECTION: MCTA

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics A Study Section[MCTA]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

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

ORG_CITY: BALTIMORE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Summary Retinal/choroidal vascular diseases including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and proliferative diabetic retinopathy (PDR) are prevalent causes of vision loss. Vascular endothelial growth factor-A (VEGF-A) is a key stimulator and intraocular injections of VEGFA antagonists provides great benefits. However, outcomes are suboptimal because other vasoactive factors contribute in some patients and because patients and physicians have difficulty maintaining the frequency of injections needed to control neovascularization (NV) and exudation. While Faricimab, which targets both VEGF-A and angiopoietin 2, may have slightly greater durability than specific VEGF-A antagonists, it does not provide better efficacy and there are many patients treated with Faricimab who have suboptimal outcomes. Treatments that target other contributing factors in addition to VEGFA and provide sustained release to reduce treatment burden are needed and this proposal addresses both of those needs. In the previous grant period, we demonstrated that AXT107, a collagen IV-derived 20-mer peptide mimetic, strongly suppresses NV and vascular leakage in models relevant to nAMD, DME, and PDR and elucidated part of its mechanism of action; it binds integrins αvβ3 and α5β1 and blocks their co-receptor functions resulting in suppression of VEGF and hepatocyte growth factor (HGF) signaling and conversion of angiopoietin 2 (Ang2) from a Tie2 antagonist to a Tie2 agonist. When injected into the vitreous of rabbits, AXT107 self-aggregated into a gel that slowly eroded providing sustained release and prolonged suppression of NV and vascular leakage. This led to clinical trials in nAMD and DME which demonstrated sustained suppression of exudation in many patients, but in some patients the gels were not compact and fragmented, resulting in dispersion of particles into the anterior chamber, occluding trabecular meshwork and increasing intraocular pressure. These studies have helped to validate αvβ3 and α5β1 as important therapeutic targets, but also demonstrated that more knowledge is needed to better understand exactly how they interact with RTKs, which interactions are important, and rationally design an antagonist that can be provided by sustained delivery. AXT107 is still a clinical candidate if a new sustained delivery approach can be developed, but in addition, it provides a tool along with newly developed analogs to further explore the mechanism by which antagonism of αvβ3 and α5β1 suppresses NV and exudation providing new knowledge that can guide development of improved next generation antagonists of αvβ3 and α5β1. Thus, this proposal will explore detailed mechanisms by which signaling through αvβ3 and α5β1 promote retinal/choroidal NV and exudation and how best to utilize that knowledge for design of therapeutic peptides, while at the same time solving issues related to delivery of AXT107 to allow additional clinical testing.

PI_NAMEs: CAMPOCHIARO, PETER A (contact)

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: Address;Agonist;analog;Angiopoietin-2;Animal Model;antagonist;anterior chamber;Antibodies;bevacizumab;Binding;Binding Sites;Blindness;Blood Vessels;Choroidal Neovascularization;clinical candidate;Clinical Trials;Collagen;Collagen Type IV;design;Development;diabetic;Diabetic Retinopathy;EGF gene;EGF-Like Domain;Endothelial Cells;Extravasation;Exudate;Exudative age-related macular degeneration;Flow Cytometry;Formulation;Frequencies;Gel;Grant;HGF gene;Immunofluorescence Immunologic;improved;In Vitro;in vivo;Injections;Integrin alpha5beta1;Integrin alphaVbeta3;Integrin Binding;Integrins;KDR gene;Knowledge;Label;Ligands;macular edema;Medical;MET gene;Modeling;Molecular Conformation;Molecular Mechanisms of Action;mouse model;neovascularization;next generation;ocular neovascularization;Oryctolagus cuniculus;Outcome;particle;Particulate;Pathway interactions;Patients;peptide drug;Peptides;peptidomimetics;Phosphorylation;Physicians;Physiologic Intraocular Pressure;Platelet-Derived Growth Factor Receptor;Play;proliferative diabetic retinopathy;ranibizumab;rational design;receptor function;Recurrence;research clinical testing;Retina;Role;Signal Transduction;targeted treatment;Therapeutic;therapeutic target;therapy development;Time;TNFSF15 gene;tool;Trabecular meshwork structure;Vascular Diseases;Vascular Endothelial Growth Factors;vasoactive agent;VEGFA gene;Vision

PROJECT_TITLE: Integrin-binding Peptide for Ocular Neovascularization and Macular Edema: Molecular Mechanism of Action

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: PROJECT NARRATIVE The multi-disciplinary Center for Climate and Health Equity (CECHE) at the University of Illinois Chicago supports cutting edge multidisciplinary research to find solutions and combat the unfair impacts of climate change among vulnerable urban populations. CECHE directly responds to community priorities (asthma, flooding and air quality) through green-infrastructure and health policy research.

PI_NAMEs: MALECKI, KRISTEN MARY CHOSSEK (contact)

PROGRAM_OFFICER_NAME: GILLMAN, ARIELLE SAMANTHA

PROJECT_TERMS: Acceleration;Address;adverse pregnancy outcome;Advisory Committees;Air;Air Pollution;Architecture;Asthma;Cardiovascular Diseases;Career Mobility;Chicago;Cities;citizen science;Climate;climate change;climate impact;climate science;climate-related health;Collaborations;combat;Communication;Communities;community advisory board;community collaboration;community engagement;Community Health;Community of Practice;Community Outreach;community partners;Data;Data Analyses;data dissemination;data platform;Data Science Core;Data Scientist;Decision Making;design;Disparity;Electronic Health Record;Emergency department visit;Ensure;Environmental Health;environmental justice;Environmental Risk Factor;Epidemiologist;epigenetic aging;Equity;Evaluation;Faculty;fine particles;Floods;Forestry;Fostering;future implementation;Goals;Green space;Health;health assessment;Health Benefit;health equity;health equity promotion;Health equity research;Health Hazards;health inequalities;health literacy;Health Personnel;Health Policy;Health Promotion;Health Sciences;Healthcare;heat island;high risk;Hospitalization;Illinois;Imagery;implementation science;indexing;Infrastructure;infrastructure development;innovation;Institution;Interdisciplinary Study;land cover;land use;Life Expectancy;Link;Mental Health;metropolitan;Minority-Serving Institution;Mission;Modeling;Modernization;multidisciplinary;Nature;Neighborhoods;next generation;Occupational Health;Outcome;Ozone;Perception;Physicians;Pilot Projects;Policies;Policy Developments;Policy Maker;Policy Research;Pollen;Population;Process;programs;Public Health;Public Health Schools;Reduce health disparities;Research;Research Design;Research Personnel;Research Project Grants;resilience;response;Risk;Science;Scientist;social;Social Mobility;spatiotemporal;success;System;Thinking;Time;Trainers Training;Training;Translational Research;Translations;Trees;United States;United States National Institutes of Health;Universities;urban area;Urban Community;Urban Health;urban planning;Urban Population;Vision;Volatilization;vulnerable community;Work

PROJECT_TITLE: Center for Climate Health Equity (CECHE)

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 LWJ-K (C2)]


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Social Determinants of Health

PROJECT_TERMS: Acceleration;Address;Advocate;anti-cancer research;Area;Award;Awareness;Biological Sciences;career development;Career Mobility;Chicago;climate change;climate impact;climate science;climate-related health;Clinical;college;Communities;community collaboration;community engagement;Community Outreach;community partners;Complex;Data;data integration;Discipline;Educational workshop;Engineering;Ensure;environment related cancer;Environmental Engineering technology;Environmental Exposure;Environmental Health;environmental justice;Epidemiologist;Equity;evidence base;Fostering;Goals;Government;Grant;Growth;Health;health assessment;health equity;health equity promotion;Health equity research;Healthcare;improved;Infrastructure;innovation;Interdisciplinary Study;Intervention;Leadership;Medical;Medicine;metropolitan;Mission;Monitor;multidisciplinary;Nature;Outcome;Peer Review;Persons;programs;promote resilience;Public Health;Publications;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;Science;Services;social media;Structure;success;symposium;Training;Translational Research;United States;United States National Institutes of Health;Urban Community;urban planning;Urban Population;Vision;web site;Work;Writing

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Cardiovascular;Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

PI_NAMEs: KIM, HONGHYOK  (contact)

PROJECT_TERMS: Address;Adverse effects;adverse pregnancy outcome;Aging;Air;Air Pollution;Architecture;Area;Attenuated;Biodiversity;built environment;Cardiopulmonary;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;Censuses;Characteristics;Chicago;Cities;Climate;climate change;climate impact;climate-related health;Communities;Community Health;community living;community partners;Complex;criteria air pollutant;Data;Data Set;density;design;Disasters;Disease Outcome;Disparity;Economic Development;Elements;Emergency department visit;Energy consumption;Engineering;Environmental Exposure;Environmental Hazards;environmental justice;Environmental Risk Factor;Epidemiology;epigenetic aging;evidence base;Exposure to;fine particles;Floods;forest;Green space;Health;Health Benefit;health disparity;health equity;Heat Waves;High temperature of physical object;Hispanic;Hospitalization;Hour;Hurricane;improved;Incidence;Individual;Industrialization;Infrastructure;Intervention;land use;Link;local economy;Location;Measures;Mediating;Mental Health;meter;minority communities;Modeling;Nature;Neighborhoods;non-Native;Not Hispanic or Latino;Outcome;outcome disparities;Ozone;Pathway interactions;Patients;Pattern;Plants;Poaceae;Policies;Property;Public Health;Rain;Recording of previous events;remote sensing;Research;Research Project Grants;Research Project Summaries;respiratory;Respiratory Disease;response;Risk;Risk Factors;risk mitigation;Science;sensor;Shapes;Site;social capital;sociodemographics;spatiotemporal;stem;Stratification;Structural Racism;Temperature;Time;time use;Translational Research;Transportation;Trees;trend;tropospheric ozone;urban area;Urban Community;urban planning;Urban Population;Work

PROJECT_TITLE: Research Project: Evaluating Green Infrastructure Impacts on Climate Change Related Heat, Air Quality, Flooding, and Cardiopulmonary Outcomes in Chicago


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Social Determinants of Health

PI_NAMEs: CHRIQUI, JAMIE F (contact)

PROJECT_TERMS: Address;Air;Area;Asthma;Characteristics;Chicago;Cities;citizen science;Climate;climate change;climate impact;climate science;climate-related health;Communication;Communities;community engagement;community organizations;Community Outreach;community partners;County;data access;Data Analyses;design;Development;Ensure;Environmental Health;Environmental Impact;environmental justice;Environmental Risk Factor;Equipment and supply inventories;Equity;Evaluation;experience;Floods;Future;Goals;hazard;Health;health equity;health equity promotion;Health equity research;health knowledge;Health Personnel;Health Sciences;Healthcare;Heart;implementation science;improved;indexing;Industrialization;Inequity;Infrastructure;innovation;Institutionalization;interest;Knowledge;Leadership;member;Modeling;Municipalities;Nature;Neighborhoods;novel;novel strategies;Outcome;Persons;Policies;Policy Maker;prevent;Process;programs;Public Health;Qualitative Research;Research;research and development;Research Personnel;Research Priority;Research Project Grants;resilience;response;Scientist;Shapes;Side;social factors;symposium;Time;tool;Trainers Training;Translating;United States;Urban Community;urban planning;Urban Population;Voice;Work;working group

PROJECT_TITLE: Community Outreach and Engagement Core


PI_NAMEs: BASU, SANJIB  (contact)

PROJECT_TERMS: Address;Air Pollution;ambient air pollution;Architecture;Chicago;Child;citizen science;Climate;climate change;climate impact;climate science;climate-related exposures;climate-related health;Collaborations;Communication;Communities;community academic partnership;community building;community collaboration;community engagement;Community Outreach;community partners;community research;Complex;computer network;Computer software;Data;data acquisition;Data Analyses;Data Collection;data resource;Data Science;Data Security;Data Set;Databases;Dedications;design;Development;diverse data;Engineering;Environmental Health;Environmental Risk Factor;environmental stressor;Epidemiology;Equity;Floods;Forestry;Foundations;Goals;Growth;Health;health care service utilization;health data;health equity;health literacy;Health Personnel;Health Policy;Infrastructure;innovation;interdisciplinary collaboration;land use;Life Cycle Stages;Maps;Mission;Modeling;multidisciplinary;Nature;novel;organizational structure;Outcome;Output;Pilot Projects;Play;Policy Maker;Pollen;Pollution;population health;Public Health Schools;repository;Research;Research Personnel;Research Project Grants;Resolution;Resources;Role;Science;Scientist;Secure;spatiotemporal;Time;tool;Training;Underserved Population;Urban Community;urban planning;virtual;Work

PROJECT_TITLE: Geospatial Data Analysis Core


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Comparative Effectiveness Research;Cost Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Nutrition;Obesity;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

PHR: PROJECT NARRATIVE Policymakers lack critical evidence on the effects of promising interventions to address food and nutrition insecurity because of no available evidence on long-term population health, effects on health disparities, and cost-effectiveness. Using our NIH-funded, validated, state-of-the-art, and dynamic microsimulation model, this project will measure the longer-term health outcomes, health equity, and economic impact of four highly promising policy interventions to address food and nutrition insecurity on the US adult population and across racial/ethnic and socioeconomic groups. This proposal seeks to fill these gaps by improving our understanding of the health equity and economic effects of different food and nutrition interventions and providing important evidence to support national priorities around diet-related diseases and health disparities.

PI_NAMEs: KIM, DAVID DAEHO (contact)

PROGRAM_OFFICER_NAME: MARSHALL, VANESSA J

PROJECT_TERMS: Acceleration;Accounting;Address;Adult;Advocacy;Affect;Body mass index;Cardiovascular Diseases;Caregivers;Characteristics;Clinical;comparative effectiveness;cost;cost effective;cost effectiveness;Cost Effectiveness Analysis;cost-effectiveness ratio;Counseling;COVID-19 pandemic;Data;Diabetes Mellitus;Diet;dietary;Dietary Intervention;Disease;disease disparity;Disparity;disparity reduction;economic impact;economic outcome;Economics;Education;Effectiveness;Eligibility Determination;ethnic minority population;Ethnic Origin;evidence base;Food;Food Access;food insecurity;Food Policy;Funding;Future;Glycosylated hemoglobin A;Government;Government Agencies;Health;Health Benefit;Health Care Costs;health disparity;health economics;health equity;Health Policy;Health Promotion;Healthcare;implementation cost;improved;incentive program;Incidence;Income;incremental cost-effectiveness;Individual;innovation;Insurance Coverage;Intervention;intervention effect;knowledge translation;Legal;Life Style;Long-Term Effects;low socioeconomic status;Measures;Minority Groups;Modeling;models and simulation;mortality;multidisciplinary;National Health and Nutrition Examination Survey;National Institute on Minority Health and Health Disparities;nutrition;Nutrition Policy;Nutritional;Obesity;Online Systems;Outcome;Patient Self-Report;Patients;Personal Satisfaction;Policies;Policy Maker;Population;population based;population health;Population Intervention;Positioning Attribute;Price;primary outcome;Productivity;Public Health;Race;racial minority population;Reduce health disparities;Reporting;Research;Risk;rural area;screening;Security;Societies;Socioeconomic Factors;Socioeconomic Status;socioeconomics;Subgroup;Time;Uninsured Medical Expense;United States Department of Agriculture;United States National Institutes of Health;uptake;Weight

PROJECT_TITLE: Modeling Health Equity and Economic Impacts of National Strategies to Address Food and Nutrition Insecurity

STUDY_SECTION: SSPB

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Cancer;Emerging Infectious Diseases;Genetics;Immunotherapy;Infectious Diseases;Influenza;Pneumonia and Influenza

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: NARRATIVE CD4+ T cells play key roles in orchestrating immune responses to infections and cancers and have been implicated in most autoimmune diseases. Key to their participation in these settings is activation by antigen- derived peptides that are produced by an array of poorly understood intracellular pathways. We propose to identify these pathways using a variety of complementary techniques and highly customized reagents, with an eye to enhancing rational vaccine design and treatments for autoimmune diseases and cancers.

PI_NAMEs: EISENLOHR, LAURENCE CRANE (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: adaptive immune response;adaptive immunity;Anabolism;anti-cancer;Antibodies;Antigen Presentation Pathway;Antigen-Presenting Cells;Antigens;Autoimmune Diseases;B-Lymphocyte Epitopes;Binding;cancer immunotherapy;CD4 Positive T Lymphocytes;Cell Line;Cell surface;cell type;Cells;Complex;CRISPR/Cas technology;Cytoplasm;Data;Dendritic Cells;Disparate;Early Endosome;Endosomes;Epitopes;extracellular;Eye;Fibroblasts;Flow Cytometry;gene product;Gene set enrichment analysis;Generations;Genes;genome-wide;high throughput screening;Histocompatibility Antigens Class II;Immune response;Immunofluorescence Microscopy;Immunoprecipitation;in vivo;Infection;Infectious Agent;Influenza;insight;Investigation;Knock-out;knockout gene;late endosome;Libraries;Location;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Modality;Modeling;mouse genome;novel;Outcome;pathogen;Pathway interactions;Peptide Hydrolases;Peptides;Play;Population;Process;Production;Proteins;Proteolysis;Reagent;reconstitution;Recycling;Resolution;response;Role;Route;screening;Screening Result;Small Interfering RNA;small molecule;Sorting;Surface Antigens;symposium;System;T-Cell Receptor;targeted sequencing;Techniques;Testing;therapeutic development;Tumor Immunity;Vaccine Design;vaccine efficacy;Validation;Viral;virtual;Work

PROJECT_TITLE: Defining the four major routes of MHC class II antigen processing and presentation with influenza antigens

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


NIH_SPENDING_CATS: Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Many neurodevelopmental disorders result from mutations in proteins that regulate transcription, particularly those that control histones. Histones wrap DNA into complex structures to regulate transcription and are modified by posttranslational modifications, which help to control this process. We propose to study how disruption of these modifications affects neuronal function and leads to neurodevelopmental deficits.

PI_NAMEs: KORB, ERICA MEGAN (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Acetylation;Address;Affect;Animal Behavior;Animal Model;Behavior;Behavioral;behavioral outcome;Biochemical;Brain;Catalytic Domain;causal variant;Cell model;Cells;Chromatin;Cognition;cognitive change;Cognitive deficits;Complex;Data;de novo mutation;Deposition;Development;Developmental Delay Disorders;Disease;Dissociation;DNA;Embryo;Enzymes;Epigenetic Process;ES Cell Line;experimental study;Frameshift Mutation;Gene Expression;Genes;Genetic;Genetic Transcription;Genome;genome-wide;Genomics;Goals;Growth;Heterozygote;histone methyltransferase;Histones;insight;Intellectual functioning disability;Knock-out;Knockout Mice;loss of function mutation;Lysine;Measures;Methylation;Methyltransferase;Microcephaly;Modeling;Modification;Mouse Embryonic Stem Cells;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;Neurodevelopmental Deficit;Neurodevelopmental Disorder;neurogenesis;neuron development;Neuronal Differentiation;Neurons;patient population;Patients;Play;Positioning Attribute;Post-Translational Protein Processing;prevent;Process;Proteins;recruit;Regulation;RNA Splicing;Role;single nucleus RNA-sequencing;stem cell model;Structure;Synapses;System;Testing;tool;Variant;Vertebral column;Work

PROJECT_TITLE: The role of chromatin regulators in neurodevelopmental disorders

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


ORG_CITY: LA JOLLA

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE: Transient cerebral ischemia occurs in many clinical settings, including transient ischemic attack, cardiac arrest, hypovolemic shock, etc. Most cerebral ischemia survivors have long-term neurological sequelae due to brain ischemia reperfusion injury. This proposal will use state-of-the-art animal models and advanced imaging technologies to study the underlying mechanisms and corresponding treatment strategies for brain ischemia reperfusion injury.

PI_NAMEs: HU, BINGREN  (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: 3-Dimensional;Affect;Animal Model;Apoptosis;Apoptotic;Astrocytes;ATP phosphohydrolase;Autophagocytosis;Autophagosome;Brain;Brain Edema;Brain Ischemia;Cardiac Surgery procedures;Cell Death;Cellular Membrane;Cerebral Ischemia;Clinical;Complement;Data;Deposition;Ethylmaleimide;Eukaryotic Initiation Factor-2;Event;Exhibits;experience;Foundations;Functional disorder;Genetic Models;Heart Arrest;Hypovolemia;Hypovolemic Shock;Hypovolemics;Imaging technology;Impairment;Inflammatory Response;inhibitor;Ischemia;Lysosomes;Macrophage;Mediating;Medical;Membrane Fusion;Microglia;Mitochondria;Modeling;Molecular Chaperones;mouse model;Mus;N-ethylmaleimide-sensitive protein;Neurologic;neuron loss;Neurons;neuropathology;novel;Organelles;overexpression;Oxygen;Parkin;Pathway interactions;Peptides;pharmacologic;Phenotype;protein aggregation;Proteins;Reperfusion Injury;Research;Role;Science;SIRT1 gene;SNAP receptor;soluble NSF attachment protein;Structure;Survivors;Testing;Therapeutic;tool;Transient Cerebral Ischemia;Transient Ischemic Attack;treatment strategy;Vasospasm;Wild Type Mouse

PROJECT_TITLE: Dysfunctional organelle-specific autophagy leads to brain ischemia-reperfusion injury

STUDY_SECTION: BINP

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


ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

PHR: Project Narrative  The mammalian cell cycle is commonly conceived as a hard-wired pathway, but emerging work indicates that the cell cycle is much more plastic than is generally believed, with multiple routes to cell division under different conditions. The proposed project uses single-cell time-lapse microscopy and cell tracking to determine how cells are able to rapidly adapt to inhibition of a key cell-cycle regulator called CDK2. The proposed work will reveal how the cell cycle is wired for success even in the face of perturbations, which may identify ways to improve the therapeutic efficacy of targeted cell-cycle inhibitors to treat human disease.

PI_NAMEs: SPENCER, SABRINA LEIGH (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Acute;Automobile Driving;Binding;Biological Assay;Breast Cancer Treatment;CCNE1 gene;CDC2 gene;CDK2 gene;CDK4 gene;Cell Cycle;Cell Cycle Completion;Cell Cycle Progression;Cell division;Cell Line;Cell Proliferation;cell type;Cells;Computer Models;Cyclin A;cyclin A2;Cyclin D1;Cyclin-Dependent Kinase Inhibitor;Cyclin-Dependent Kinases;Cyclins;Data;Dependence;Development;Docking;Drug resistance;E2F transcription factors;Enzymes;experimental study;Feedback;Genetic Transcription;Goals;Hour;human disease;Image;improved;In Vitro;inhibitor;kinase inhibitor;Malignant Neoplasms;Mammalian Cell;Measures;Methods;Microscopy;Molecular;Monitor;novel;Null Lymphocytes;overexpression;Pathway interactions;Pharmaceutical Preparations;Pharmacotherapy;Phosphorylation;Phosphotransferases;Pliability;Positioning Attribute;pressure;prevent;Proliferating;Proteins;Research;Resistance;response;retinoblastoma tumor suppressor;Role;Route;sensor;small molecule;success;Technology;Testing;Time;tool;Treatment Efficacy;Up-Regulation;Visualization;Work

PROJECT_TITLE: Molecular basis of cell-cycle plasticity and robustness

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]