PHR: The prevalence of obesity is increasing in the United States and worldwide with significant negative effects to both health and the economy. This study will evaluate and improve three new minimally invasive image-guided therapies for morbid obesity in which interventional techniques are used to suppress the body's signals for feeling hungry, leading to weight loss. Our goal is to use new imaging techniques and devices to make these procedures safe, accurate and effective.

PI_NAMEs: KRAITCHMAN, DARA L (contact);WEISS, CLIFFORD RAABE

PROGRAM_OFFICER_NAME: ANDERSEN, DANA K

PROJECT_TERMS: 90Y;Address;Affect;American;Animal Model;Animals;appetite loss;Arterial Embolization;Attenuated;bariatric surgery;Bariatrics;Biliary;Blood Vessels;Body mass index;Body Weight decreased;Brain;cancer therapy;canine model;Canis familiaris;Catheters;Cells;Client;Clinical;Clinical Trials;clinically relevant;Complex;cone-beam computed tomography;cost;Cryosurgery;Data;Desire for food;Diabetes Mellitus;Diameter;Disease;Embolism;Encapsulated;Endocrine;Equipment;Esophagogastric Junction;Family suidae;Feeling;Funding;Fundus;gastric artery;gastric fundus;Gastric ulcer;Gastrins;Gastritis;ghrelin;glucagon-like peptide 1;Goals;Grant;Health;Heart Diseases;heat injury;Hormonal;Hormones;Human;Hunger;Hyperthermia;hyperthermia treatment;Image;image guided;image guided therapy;Imaging Device;Imaging Techniques;improved;Incidence;increased appetite;Injury;Intervention;Intestines;iron oxide nanoparticle;Ischemia;joint stress;Label;Liver;Location;Magnetism;Malignant Neoplasms;Medical Care Costs;meter;Microfluidic Microchips;Microfluidics;Microspheres;minimally invasive;Modeling;Morbid Obesity;novel;novel strategies;obese patients;Obesity;obesity treatment;Operative Surgical Procedures;Organ;Overweight;Pancreas;Patients;Perforation;Persons;Phase I Clinical Trials;Prevalence;Procedures;Production;Progress Reports;Radioactive;Radioembolization;Radiolabeled;reconstruction;Reflux;Risk;Safety;Satiation;Serious Adverse Event;Signal Transduction;soft tissue;Spinal Diseases;Spleen;Stomach;Structure;success;targeted delivery;Techniques;Testing;Therapeutic Embolization;Translating;translation to humans;Translations;tumor;Ulcer;United States;Vagus nerve structure;Vascular blood supply;Vascular Diseases;Weight;Weight Gain

PROJECT_TITLE: Image-guided Bariatric Arterial Embolization (BAE) for the Treatment of Obesity

STUDY_SECTION: IGIS

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


ADMINISTERING_IC: AI

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza

ORG_CITY: ROCHESTER

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Project Narrative Immune cells can sense the changing levels of proteins and produce antibodies to protect host from virus infection. This response involves a complex network of signaling molecules. We aim to understand how this signaling network is organized to respond to the changing concentration of proteins so that we can design better strategies to improve immune defense against virus infection.

PI_NAMEs: ZENG, HU  (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: 2019-nCoV;Address;airway immune response;Allergens;amino acid metabolism;Amino Acids;anti-influenza;Antibodies;Antibody Formation;Antibody Therapy;Autophagocytosis;B-Cell Activation;B-Lymphocytes;Cells;Complex;COVID-19;Data;design;Development;dietary;Event;Extracellular Signal Regulated Kinases;Family;Fatty Acids;FRAP1 gene;gain of function;Genetic;Glucose;Guanosine Triphosphate Phosphohydrolases;Humoral Immunities;Immune;Immune response;Immunity;Immunization;immunoregulation;improved;In Vitro;in vivo;Infection;influenza infection;influenzavirus;Interferons;Intervention;Knock-in Mouse;Knock-out;Leucine Zippers;Link;loss of function;Mediating;member;Metabolic;Metabolism;metabolomics;Microphthalmos;Modeling;Molecular;Molecular Target;mouse model;novel;Nutrient;Nutritional;pathogen;Pathway interactions;Proteins;Proteomics;Reaction;Regulation;Research;respiratory;Respiratory syncytial virus;response;Route;screening;sensor;Signal Transduction;Signaling Molecule;Structure of germinal center of lymph node;Technology;Testing;transcription factor;Viral Respiratory Tract Infection;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Context dependent amino acid availability and sensing determines humoral immunity

STUDY_SECTION: CMIB

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


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

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

ORG_CITY: AUSTIN

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: Project Narrative The proposed study is designed to examine the contributions of urban planning decision and inequitable exposures to particular air pollution sources to racial and ethnic disparities in asthma. The results will fill a gap that is crucial for advancing air pollution regulation and urban planning to shrink asthma disparities.

PI_NAMEs: MATSUI, ELIZABETH C. (contact)

PROGRAM_OFFICER_NAME: QUINN, ASHLINN KO

PROJECT_TERMS: Adult;Affect;Air;Air Pollution;Asthma;Black Populations;Black race;Characteristics;Child;Childhood;Childhood Asthma;Cities;Communities;County;Data;Data Collection;Data Set;design;Development;Disparity;Emergency department visit;environmental disparity;environmental health disparity;environmental justice;ethnic disparity;ethnic minority;Ethnic Origin;evidence base;experience;Exposure to;Face;fine particles;Fostering;Green space;Hazardous Waste;Health;health disparity;Healthcare;Home;hospitalization rates;Individual;Inequity;Intervention;Latinx;Latinx population;Link;Location;Lung;Lung Diseases;lung health;Measures;Minority;minority communities;Modeling;Morbidity - disease rate;neighborhood disadvantage;Neighborhoods;novel strategies;Outcome;Pattern;Policies;Population;Positioning Attribute;Power Plants;pulmonary function;Pulmonary Inflammation;Race;racial disparity;racial minority;Regulation;Research;Risk;Risk Factors;segregation;sociodemographics;socioeconomic disadvantage;Source;success;Testing;Texas;urban planning;Work

PROJECT_TITLE: Urban planning, siting of air pollution sources, and asthma disparities

STUDY_SECTION: IRAP

STUDY_SECTION_NAME: Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section[IRAP]


ADMINISTERING_IC: HL

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Atherosclerosis;Biotechnology;Cardiovascular;Clinical Research;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Prevention;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: BALTIMORE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Atherosclerotic cardiovascular disease (ASCVD) is a challenging and highly prevalent human disease that has a major genetic component, but many of the identified genetic risk loci for the disease remain unexplored with unknown target genes or tissues in which they act. In my prior work I have used human genetic data from multiple individuals and discovered that one of those uncharacterized genetic loci affects a new gene in endothelial cells called REST. This proposal will use novel laboratory genetics methods that manipulate endothelial cells in the lab and a genetic mouse model of REST inactivation to understand how our DNA affects REST in endothelial cells and how REST can affect the walls of our arteries to cause ASCVD.

PI_NAMEs: ARVANITIS, MARIOS  (contact)

PROGRAM_OFFICER_NAME: CHEON, YEWON

PROJECT_TERMS: Advisory Committees;Affect;Alleles;angiogenesis;Aorta;Arteries;Atherosclerosis;Award;Bayesian Method;Binding Sites;Biology;Blood Vessels;cadherin 5;Cardiovascular Diseases;cardiovascular disorder risk;causal variant;Cause of Death;Cellular Assay;Cessation of life;chromatin immunoprecipitation;Chromosome 4;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Coronary Arteriosclerosis;Coronary heart disease;CRISPR/Cas technology;Data;data integration;Data Set;Dependovirus;design;Development;Disease;disorder risk;Distal;Distant;DNA;effective therapy;Endothelial Cells;Endothelium;Enhancers;Enterobacteria phage P1 Cre recombinase;Epigenetic Process;experimental study;Exposure to;factor A;Funding;Future;Gene Silencing;Gene Targeting;Genes;Genetic;genetic analysis;genetic approach;Genetic Risk;genetic variant;genome editing;genome wide association study;genomic locus;Genomics;Genotype;Heritability;High Fat Diet;Human;human disease;Human Genetics;human stem cell-derived;human stem cells;Immunofluorescence Immunologic;In Vitro;in vivo;Individual;inducible Cre;Injections;insight;Investigation;K-Series Research Career Programs;Knock-out;Knockout Mice;Laboratories;LoxP-flanked allele;Matrix Metalloproteinases;Mediating;men;Mentors;Mesenchymal;Methods;migration;mouse model;multidisciplinary;Multiomic Data;Mus;Neural Cell Adhesion Molecule L1;NOS3 gene;novel;novel therapeutics;overexpression;Pathway Analysis;Pathway interactions;PECAM1 gene;Permeability;Phenotype;Physicians;Population;Postdoctoral Fellow;programs;Proteins;Public Health;Publishing;Research;Research Personnel;response;Rest;risk variant;Role;Scientist;single cell ATAC-seq;single-cell RNA sequencing;Site;skills;Small Interfering RNA;SOX18 gene;stem cell differentiation;success;Tamoxifen;Testing;Time;Tissues;transcription factor;transcription factor USF;transcriptome;transcriptome sequencing;Translating;United States;Untranslated RNA;Variant;Vascular Endothelial Cell;Vascular Endothelium;Woman;Work

PROJECT_TITLE: From genotype to phenotype in a GWAS locus: the role of REST in atherosclerosis

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(OA)]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: MARIETTA

ORG_NAME: PRODA BIOTECH, LLC

ORG_STATE: GA

PHR: This research project develops and tests a novel protein agent for pancreatic cancer treatment.

PI_NAMEs: LIU, ZHI-REN  (contact)

PROGRAM_OFFICER_NAME: FRANCA-KOH, JONATHAN C

PROJECT_TERMS: Adenocarcinoma;advanced disease;Aftercare;angiogenesis;Animal Model;anticancer activity;Binding Sites;Biopsy;Biopsy Specimen;Biotechnology;Blood Vessels;Buffers;cancer cell;Cancer Cell Growth;Cancer Model;Cancer Patient;cancer therapy;CASP8 gene;Cell secretion;Cell Survival;Cells;Clinical;Clinical Research;cohort;Collagen;commercialization;cytokine;Cytoplasmic Tail;Data;Data Set;density;Deposition;design;Desmoplastic;Development;Diagnosis;Disease;Dose;drug action;drug candidate;Drug Delivery Systems;drug mechanism;Drug resistance;effective therapy;Endothelial Cells;Enrollment;experimental study;Extracellular Matrix;first-in-human;Foundations;Future;gemcitabine;Genetically Engineered Mouse;Goals;Grant;Histologic;Hypoxia;improved;Induction of Apoptosis;innovation;Integrin alphaVbeta3;Integrins;invention;KPC model;Legal patent;Licensing;Life;Ligand Binding;Malignant neoplasm of pancreas;Malignant Neoplasms;Maximum Tolerated Dose;Mission;Monkeys;mouse model;Mus;Neoplasm Metastasis;Neoplasms in Vascular Tissue;novel;novel strategies;novel therapeutics;Nude Mice;Paclitaxel;pancreatic cancer patients;Pancreatic Diseases;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;pancreatic neoplasm;pancreatic PDX models;pancreatic stellate cell;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phase;phase 2 study;Phase I Clinical Trials;pre-clinical;preclinical study;prevent;Property;Protein Engineering;Proteins;rational design;Rattus;Recommendation;recruit;Research;Research Project Grants;Resistance;response;Safety;Sampling;Site;Small Business Technology Transfer Research;standard of care;Study models;Supporting Cell;Survival Rate;targeted agent;Technology;Testing;Therapeutic;therapeutic protein;Toxic effect;Translating;Treatment Failure;Treatment-related toxicity;tumor;Tumor Angiogenesis;tumor progression;Tumor Promotion;tumorigenic;Universities;Validation;Xenograft procedure

PROJECT_TITLE: Development of a protein drug for pancreatic cancer treatment


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cannabinoid Research;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse

ORG_CITY: WASHINGTON

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: PROJECT NARRATIVE The overall goal of this research is to inform regulatory efforts to minimize marijuana (MJ) use in disproportionately- impacted populations, in states with legalized recreational MJ and those that subsequently legalize it; this proposal’s immediate objective is to examine the recreational MJ market, MJ use, and related perceptions in market segments of diverse young adults. Our scientific premise builds on literature that indicates that licit drug retail marketing – both brick- and-mortar and online – target certain populations (e.g., young adults, racial/ethnic and sexual/gender minority groups) and the negative consequences of such retail on substance use in these groups; based on existing evidence, our central hypothesis is that exposure to MJ retailers and their marketing, advertising strategies targeting specific consumer market segments (defined by key sociodemographics or psychographics), and increased availability of products and promotions may contribute to increased MJ use in these groups. We include dissemination plans to translate tools/findings to practice.

PI_NAMEs: BERG, CARLA J (contact);CAVAZOS-REHG, PATRICIA A

PROGRAM_OFFICER_NAME: CREAMER, MELISA RAY

PROJECT_TERMS: Accounting;Address;Adult;Advertising;Age;Alcohols;Attitude;Cannabis;Cannabis policy;Cannabis retail;Cities;Complex;consumer behavior;Consumption;Data Sources;Demography;density;Diffusion of Innovation;Disparity;Dose;Environment;Epidemiology;ethnic minority;Ethnic Origin;Exposure to;gender minority;gender minority group;Goals;Health;Health Campaign;health warning;high risk;high risk population;Illicit Drugs;Industry;infancy;innovation;Interview;Label;Legal;Life Style;Literature;Location;Longitudinal Studies;Los Angeles;Marijuana;marijuana legalization;marijuana use;Marketing;Measures;Medical;Medical Marijuana;medical specialties;Medicine;Methods;Minority;minority children;Minority Status;Monitor;multidisciplinary;Neighborhoods;Outcome;Perception;Persons;Pharmaceutical Preparations;Policies;Policy Compliance;Population;Prevalence;Price;Public Health;public health research;Race;racial minority;Recreation;recruit;Regulation;Research;Risk;Sales;Sexual and Gender Minorities;social media;sociodemographics;Source;Specific qualifier value;Speed;Standardization;standardize measure;Subgroup;substance use;Surveys;Target Populations;Time;Tobacco;tool;Translating;Translational Research;Vulnerable Populations;web site;Work;young adult

PROJECT_TITLE: Recreational Marijuana Marketing and Young Adult Consumer Behavior

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HDM-T(02)]


NIH_SPENDING_CATS: Cancer;Climate-Related Exposures and Conditions;Genetics;Skin Cancer

ORG_DEPT: BIOCHEMISTRY

PHR: Project Narrative Deficiency of genes involved in nuclear excision repair (NER) has been linked to Xeroderma Pigmentosum (XP) and cancers including skin cancer, however the mechanism regulating NER is not fully understood. This application is aimed to uncover a novel And-1-mediated pathway regulating NER and skin tumorigenesis. The proposed study will help to understand how skin tumor is initiated and benefit the development of therapeutic approach to treat skin tumor.

PI_NAMEs: ZHU, WENGE  (contact)

PROGRAM_OFFICER_NAME: OKANO, PAUL

PROJECT_TERMS: Acceleration;Affect;Animal Model;Binding;Cell Cycle;Cells;chemotherapeutic agent;Chromosomal Stability;Complement;Data;DBL Oncoprotein;Dermal;design;DNA biosynthesis;DNA Damage;DNA lesion;DNA Repair;DNA-Binding Proteins;DNA-Directed DNA Polymerase;environmental mutagens;Excision Repair;experimental study;Fibroblasts;Future;gene repair;Genes;Genetic Transcription;Genome;Genome Stability;homologous recombination;in vivo;individualized prevention;Knowledge;Lesion;Ligation;Link;Malignant Neoplasms;Mammals;Mediating;Molecular;mouse model;multidisciplinary;Mus;Mutate;Mutation;novel;Nuclear;Nucleoplasm;Nucleotide Excision Repair;Nucleotides;Orthologous Gene;Pathway interactions;Patients;Phosphorylation;Physiological;Play;Polymerase;Positioning Attribute;Precision cancer therapy;Process;Protein Conformation;Proteins;recombinational repair;recruit;Regulation;Regulatory Pathway;repaired;response;Role;Series;Single-Stranded DNA;Site;Skin Cancer;Skin Neoplasms;skin squamous cell carcinoma;Skin tumorigenesis;Testing;therapeutic development;Time;Transcription-Coupled Repair;tumorigenesis;ultraviolet irradiation;ultraviolet lesions;Ultraviolet Rays;UV induced;UV induced DNA damage;Xeroderma Pigmentosum;Yeasts

PROJECT_TITLE: The role of And-1 in nucleotide excision repair

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Cerebrovascular;Childhood Injury;Clinical Research;Disability Research;Hydrocephalus;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Rare Diseases;Stroke

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROSURGERY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: RELEVANCE TO PUBLIC HEALTH This study is designed to improve our understanding of the changes in brain structure and function that result from post-hemorrhagic hydrocephalus, a form of brain injury that is common in prematurely-born infants and associated with high rates of disability and requirement for repeated neurosurgical intervention. Employing a multidisciplinary approach, we will use information from cutting-edge magnetic resonance imaging studies to identify modifiable mechanisms that underlie this disease and address long-standing clinical questions regarding the impact of neurosurgical treatment on brain development. The overarching goal is to establish an innovative line of neurosurgical treatment strategies designed to thwart the harmful effects of post-hemorrhagic hydrocephalus and support clinical trials seeking to improve outcomes in this high-risk population.

PI_NAMEs: LIMBRICK, DAVID DELMAR;SMYSER, CHRISTOPHER DANIEL (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Address;adverse outcome;Affect;Age;Anisotropy;Assessment tool;Axon;Birth;Brain;Brain Injuries;brain magnetic resonance imaging;Caring;Cerebral Palsy;Cerebrospinal fluid shunts procedure;Cerebrum;Child;Childhood;Clinical;Clinical Management;Clinical Trials;Cognitive;Cognitive deficits;cohort;Complex;Corpus Callosum;Corticospinal Tracts;Data;Data Analyses;density;design;Development;Developmental Disabilities;Diagnosis;Diffusion;Diffusion Magnetic Resonance Imaging;disability;disability risk;Disease;dysmyelination;Edema;extreme prematurity;Failure;Functional impairment;Functional Magnetic Resonance Imaging;Gestational Age;Goals;Hemorrhage;high risk population;Hydrocephalus;Image;imaging approach;imaging study;Impairment;improved;improved outcome;Individual;Infant;Infant Care;Inflammation;Injury;innovation;interdisciplinary approach;Intervention;intraventricular hemorrhage;Investigation;Link;Magnetic Resonance Imaging;Measures;Medical;Medicine;Methods;Modeling;Motor;motor impairment;MRI Scans;multidisciplinary;multimodality;myelination;Needs Assessment;Neonatal;Neonatal Intensive Care Units;neuroimaging;Neurologic;Neurologic Dysfunctions;Neurological disability;Neurological outcome;neuropathology;neurosurgery;Newborn Infant;North America;Operative Surgical Procedures;Optics;Outcome;Pathology;Patients;Pregnancy;Premature Birth;Premature Infant;Preterm brain injury;prospective;Public Health;Radiation;recruit;Research;response;Rest;Risk;Risk Factors;Role;Second Look Surgery;Shunt Device;social;spectrograph;Structure;Surgical Management;Techniques;temporal measurement;Testing;Toddler;tool;treatment strategy;ultrasound;Ventricular;Visual;white matter;Work

PROJECT_TITLE: Effects of ventricular volume and cerebral connectivity on neurological outcomes in preterm intraventricular hemorrhage

STUDY_SECTION: ANIE

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Disability Research;Nutrition;Pediatric;Physical Activity;Physical Rehabilitation;Rehabilitation

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: Poor nutrition and bedrest are common in the pediatric intensive care unit, and both practices are associated with poor outcomes in young survivors of critical illness. We propose a clinical trial to determine the feasibility of an innovative intervention that combines optimal protein delivery and early exercise in critically ill children. The results of this study will help determine the safest and most effective strategy for these interventions, and advance investigations to improve long-term, patient-centered outcomes.

PI_NAMEs: KUDCHADKAR, SAPNA R;MEHTA, NILESH M (contact)

PROGRAM_OFFICER_NAME: EVANS, MARY

PROJECT_TERMS: 1 year old;Acute;Adherence;Adverse effects;Adverse event;Age;arm;Bed rest;Beds;Caring;Child;Childhood;Clinical;Clinical Trials;Cognitive;Computers;Country;Coupled;Creatinine;Critical Illness;Critically ill children;Data;Diet;Disability Evaluation;Disease;Dose;Enrollment;Equilibrium;Equipment and supply inventories;Equipoise;Exercise;exercise regimen;exercise rehabilitation;experience;functional outcomes;functional status;Goals;Health;Image;Immobilization;Impairment;improved;Incidence;Injury to Kidney;innovation;Intake;Intervention;Investigation;lean body mass;Measurement;Measures;Mechanical ventilation;Medical;Metabolic;Mission;Morbidity - disease rate;mortality;Muscle;muscle form;Muscular Atrophy;National Institute of Diabetes and Digestive and Kidney Diseases;Nutrient;nutrition;Nutritional Study;open label;Outcome;Parenteral Nutrition;Patient-Focused Outcomes;Patients;Pediatric Intensive Care Units;Phase;Physical Exercise;Pilot Projects;pilot trial;Population;preservation;programs;Proteins;Protocol Compliance;Protocols documentation;psychologic;Public Health;quadriceps muscle;Quality of life;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Rehabilitation therapy;Reproducibility;Research Priority;Respiratory Failure;response;Safety;safety and feasibility;screening;secondary analysis;secondary outcome;Serum;Severity of illness;Site;standard care;Stereotyping;Strategic Planning;Survivors;Testing;Thick;Time;trial comparing;ultrasound;United States National Institutes of Health

PROJECT_TITLE: Protein Optimization with Exercise to Improve Muscle Mass and Functional Outcomes (PROXIMUS)

STUDY_SECTION: NMHD

STUDY_SECTION_NAME: Nutrition and Metabolism in Health and Disease Study Section[NMHD]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: American Indian or Alaska Native;Behavioral and Social Science;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Racial and Ethnic Minority Health Research;Rehabilitation;Rural Health;Social Determinants of Health;Substance Misuse

ORG_CITY: FLAGSTAFF

ORG_DEPT: MISCELLANEOUS

ORG_NAME: NORTHERN ARIZONA UNIVERSITY

ORG_STATE: AZ

PHR: PROJECT NARRATIVE This project proposes an innovative research and training program to educate advanced graduate students and current clinical service providers with knowledge, research skills and culturally-centered practices regarding substance use (SU) and substance use disorders (SUDs) that can be applied in interprofessional health care settings. The program will specifically focus on American Indian, Hispanic, and rural underserved populations in Arizona and the southwestern US; however, the skills obtained through this program can be applied to other diverse populations and regions of the US.

PI_NAMEs: BALDWIN, JULIE ANN (contact);MELLOTT, RAMONA N

PROGRAM_OFFICER_NAME: DUCHARME, LORI

PROJECT_TERMS: Achievement;addiction;Address;American Indians;Area;Arizona;behavioral health;care providers;career;Caring;Client;Clinical;clinical care;Clinical Psychology;Clinical Services;Communities;Complex;Comprehensive Health Care;Counseling;COVID-19 pandemic;design;Discipline;disparity reduction;doctoral student;Documentation;Education;Educational Curriculum;effectiveness evaluation;ethnic minority;Ethnic Population;Evaluation;evidence base;Evidence based practice;experience;Faculty;field study;Fostering;Goals;graduate student;Health;health care settings;health disparity;Health Occupations;Health Professional;Health Services Accessibility;Healthcare;Hispanic;Hispanic Populations;Individual;innovation;Institution;interdisciplinary collaboration;Intervention;Knowledge;learning outcome;Manuscripts;Mentors;Occupational Therapy;Outcome;Peer Review;Persons;Physical therapy;poor health outcome;Population Heterogeneity;practice setting;Premature Mortality;Prevention Research;Problem-Based Learning;programs;Provider;Psychology;racial minority;racial population;Recruitment Activity;Research;Research Activity;Research Personnel;Research Project Grants;Research Training;Risk;rural dwellers;rural patients;Rural Population;rural underserved;Schools;Scientist;service providers;skills;Southwestern United States;Student recruitment;Students;substance use;Substance Use Disorder;symposium;telehealth;telehealthcare;Training;Training Programs;treatment research;Underserved Population;United States;Universities;web site;Work

PROJECT_TITLE: C-CART: Culturally Centered Addictions Research Training


NIH_SPENDING_CATS: Biotechnology;Cooley's Anemia;Gene Therapy;Genetics;Hematology;Human Genome;Orphan Drug;Pediatric;Rare Diseases;Sickle Cell Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: Project Narrative 8. Project Narrative Hereditary persistence of fetal hemoglobin (HPFH) mutations reduce the severity of β-hemoglobinopathies and can be introduced experimentally and for therapeutic benefit. The aim of this proposal is to understand mechanisms of naturally occurring and therapeutically induced HPFH. Once the mechanisms are better understood, it will be possible to develop safe and effective precision medicine-based treatments for β- hemoglobinopathies.

PI_NAMEs: DOERFLER, PHILLIP A (contact)

PROGRAM_OFFICER_NAME: ROY, CINDY

PROJECT_TERMS: Address;Adult;Aneuploidy;Benign;beta Globin;beta Thalassemia;Binding;Biological Assay;career;CD34 gene;Cell division;cell fixing;Cells;Chromosomal Instability;Chromosomal Rearrangement;Chromosomal Stability;Chromosome abnormality;chromosome loss;Chromosome Segregation;Chromosome Structures;chromothripsis;Clinical;Clinical Research;clinically relevant;Collaborations;Cytology;derepression;Development;Developmental Gene;Distal;Distant;DNA;DNA Damage;DNA Double Strand Break;Elements;Ensure;Environment;Epigenetic Process;Erythrocytes;Erythroid Cells;Essential Genes;evidence base;experimental study;Fetal Hemoglobin;Foundations;functional genomics;gamma Globin;Gene Activation;Gene Expression;Gene Expression Regulation;gene therapy;Genes;Genetic Diseases;Genetic Transcription;genome editing;genome sequencing;genotoxicity;Goals;Hematopoietic stem cells;Hemoglobin;Hemoglobin F Disease;Hemoglobinopathies;Human;Immunofluorescence Immunologic;improved;In Vitro;in vivo;insight;Intercistronic Region;Investigation;K-Series Research Career Programs;Lead;Longevity;Malignant - descriptor;Maps;Mediating;Mendelian disorder;micronucleus;Molecular;Mutagenesis;Mutation;novel;novel therapeutic intervention;Nuclear Structure;Nucleic Acid Regulatory Sequences;Pathway interactions;Perinatal;pharmacologic;Point Mutation;Population;postnatal;precision medicine;preclinical study;premalignant;Process;programs;promoter;Protocols documentation;Regulation;Regulatory Element;Research;Risk;Safety;Severities;Sickle Cell Trait;single cell genomics;success;Switch Genes;telomere;Thalassemia;Therapeutic;therapeutic genome editing;therapeutic target;TP53 gene;Training;transcription factor;Variant;whole genome;Work

PROJECT_TITLE: Defining the mechanisms of hemoglobin switching and genotoxicities associated with its manipulation

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Kidney, Urologic and Hematologic Diseases D Study Section[DDK-D]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: CAMBRIDGE

ORG_DEPT: BIOLOGY

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE All cells produce a contingent of incomplete proteins due to surprisingly common errors in gene expression, and mechanisms exist to suppress these truncated protein variants, suggesting that they are highly cytotoxic; however, this proposition has not been systematically tested. In the proposed work, I will harness a powerful new method for massively parallel measurements to determine the cytotoxicity of incomplete proteins across proteomes. Combined with complementary techniques, this approach will allow me to address fundamental questions regarding the importance and function of nonsense-mediated quality control mechanisms, the roles of incomplete proteins in the bactericidal activities of antibiotics, and the evolutionary consequences of suppressing incomplete protein-coding mutations, with implications for the 10-15% of human diseases linked to premature truncation variants.

PI_NAMEs: SAVINOV, ANDREW  (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TERMS: Address;Amino Acid Sequence;Aminoglycosides;Antibiotics;Bacillus subtilis;Bacteria;bactericide;Bioinformatics;Cells;Code;Combined Antibiotics;Complex;Computer Analysis;Coupling;cytotoxic;cytotoxicity;Data;DNA;Dominant-Negative Mutation;Drug toxicity;Escherichia coli;Eukaryota;Evolution;Exhibits;Firmicutes;Gene Expression;Gene Family;Genes;Genetic Transcription;Growth;high throughput screening;human disease;innovation;Knock-out;Laboratories;Libraries;Link;Macrolides;Maps;Mass Spectrum Analysis;Measurement;Measures;Mediating;Messenger RNA;Methodology;Methods;mRNA Transcript Degradation;mutant;Mutation;Nonsense Codon;novel;Oligonucleotides;Open Reading Frames;Organism;Pathway interactions;Pharmaceutical Preparations;Pharmacotherapy;Physiological;premature;Prevalence;Process;Production;Prokaryotic Cells;Protein Biosynthesis;Protein Fragment;Protein Truncation;Proteins;Proteome;Proteomics;Pseudogenes;Puromycin;Quality Control;Resolution;rho;ribosome profiling;Ribosomes;RNA Degradation;Role;Techniques;Technology;Testing;tool;Toxic effect;transcription termination;transcriptome sequencing;Translational Repression;Translations;translatome;Variant;Work

PROJECT_TITLE: Cytotoxicity and function of incomplete proteins


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Lung Cancer;Prevention;Rural Health;Social Determinants of Health;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE The tobacco industry’s decades of manipulations to the nicotine form and length of tobacco leaf (long vs. fine cut) in moist snuff (i.e., dip) have resulted in a product with strong appeal and addictive qualities, which contributes to health inequities in Appalachia where the prevalence of use remains high. The proposed research will evaluate how level of smokeless tobacco (SLT) dependence is associated with characteristics of moist snuff (e.g., total nicotine, form of nicotine, and tobacco cut) used by adolescents and adults in Appalachian Ohio, as well as how variations to tobacco cut and nicotine form affect product use behaviors and nicotine delivery. Results will provide justifications for local, state, or federal regulations aimed at reducing the appeal and addictiveness of moist snuff.

PI_NAMEs: KELLER-HAMILTON, BRITTNEY L (contact)

PROGRAM_OFFICER_NAME: KIMMEL, HEATHER L

PROJECT_TERMS: absorption;abuse liability;Accounting;addiction;addiction liability;Address;Adolescent;Adult;Affect;Analytical Chemistry;Appalachian Region;Area;base;Behavior;Biometry;Cardiovascular Diseases;Characteristics;cohort;Crossover Design;Data Analyses;Dependence;design;Development;Disease;Disparity;Dose;Dryness;Epidemiology;Equity;Evaluation;Experimental Designs;Foundations;Genus Mentha;Goals;Health Disparities Research;health disparity;health inequalities;High Prevalence;Human;Industry;Inequity;Knowledge;Laboratories;laboratory experiment;Length;male;Malignant Neoplasms;Manufacturer;Marketing;Mentorship;Methods;Nicotine;Nicotine Dependence;Ohio;Oral health;Oral Tobacco;Outcome;Participant;Persons;Plant Leaves;Population;population based;Prevalence;Public Health;Randomized;Regulation;Research;Sales;Scientist;secondary analysis;Smokeless Tobacco;smokeless tobacco addiction;smokeless tobacco use;smokeless tobacco user;snuff;snus;social factors;Speed;Standardization;Testing;Tobacco;tobacco advertising;Tobacco Dependence;tobacco flavor;Tobacco Industry;tobacco products;tobacco regulatory science;Tobacco use;toxicant;Training;Underserved Population;United States;Variant;young adult;Youth

PROJECT_TITLE: Effects of tobacco cut and nicotine form on the abuse liability of moist snuff

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Brain Disorders;Clinical Research;Dementia;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Palliative Care

ORG_CITY: New York

ORG_NAME: SPARK NEURO INC.

ORG_STATE: NY

PHR: PROJECT NARRATIVE Research spanning recent decades has established that electroencephalography (EEG) can be an effective tool for identifying Alzheimer’s disease (AD) at an early stage. Using machine learning, SPARK Neuro is unlocking the full potential of EEG to better assess cognitive health and neurodegeneration. This neuroanalytic platform— called SPARK Scan—will be a standardized, objective, non-invasive, cost-effective diagnostic tool capable of highly sensitive and specific detection of cognitive impairment across the entire disease continuum, vastly expanding AD screening initiatives and providing neurological insights to aid in the diagnosis and tracking of disease progression.

PI_NAMEs: YODER, KEITH  (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: Acceleration;Accounting;Affect;Age;aging population;Algorithms;Alzheimer disease screening;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease diagnostic;Alzheimer's disease model;Alzheimer's disease pathology;Amyloid;Amyloid beta-42;Amyloid beta-Protein;Behavioral Symptoms;Biological Markers;burden of illness;Cerebrospinal Fluid;Classification;Clinical;Clinical Research;cloud based;Cognitive;commercialization;Computer software;Consumption;cost;cost effective;Country;Data;Dementia;Detection;Devices;Diagnosis;Diagnostic;diagnostic tool;Disease;Disease Progression;drug development;Electroencephalography;Ensure;Health;Health Care Costs;Human;human old age (65+);Impaired cognition;improved;indexing;insight;Machine Learning;machine learning algorithm;Measures;Medical;Methods;Monitor;Nerve Degeneration;Neurologic;Neurologist;novel;Older Population;Outcome Measure;Output;Pathologic;Pathology;Patient Care;Patient-Focused Outcomes;Patients;Performance;performance tests;Persons;Phase;Physicians;predictive modeling;Radiologic Health;Reporting;Research;research and development;Rest;satisfaction;Scanning;Severity of illness;Small Business Innovation Research Grant;Standardization;success;symptom management;Symptoms;System;tau Proteins;tau-1;Technology;Testing;Tissues;tool;Training;United States;Universities;Update;usability;user-friendly;Work;β-amyloid burden

PROJECT_TITLE: Developing a novel EEG-based index for evaluating amyloid and tau burden in Alzheimer's Disease


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Adolescent Sexual Activity;Clinical Research;Contraception/Reproduction;Pediatric;Prevention;Teenage Pregnancy;Women's Health Research

ORG_CITY: COLUMBIA

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it intends to identify a new and improved method of contraceptives for women. Ineffectiveness of current over-the-counter (OTC) contraceptives is one of the major contributors to the high unintended pregnancy rate in the United States. This project aims to provide a proof-of- concept outcome for a novel on-demand contraceptive that keeps semen in a gel-like state in the vagina and blocking of sperm transport in the female reproductive tract.

PI_NAMEs: MATZUK, MARTIN M.;SLAYDEN, OV D;WINUTHAYANON, WIPAWEE  (contact)

PROGRAM_OFFICER_NAME: LINDSEY, CHRISTOPHER CHARLES

PROJECT_TERMS: 3-Dimensional;Address;Adolescent;analog;Antibodies;Azoles;Back;Binding;candidate validation;Cell Survival;Cells;Cervical;cervicovaginal;Cessation of life;Chemistry;chymotrypsin;condoms;Contraceptive Agents;Contraceptive Availability;contraceptive efficacy;Contraceptive methods;DNA;Dose;Ejaculation;Elastases;Embryo;enzyme activity;Epithelial Cells;experimental study;Failure;Female;Female Contraceptive Agents;female reproductive tract;Fertility;Fertilization;Film;Fluorides;Gel;Genes;Goals;Health;healthcare burden;hormonal contraception;Human;Hyperviscosity;implantation;improved;In Vitro;in vitro Assay;in vivo;Infertility;inhibitor;innovation;Kinetics;Lead;Libraries;Liquid substance;Macaca mulatta;Male Infertility;Medical;men;Methods;Molecular;Mucous body substance;Mus;nanomolar;natural Blastocyst Implantation;nonhuman primate;novel;novel strategies;novel therapeutics;Outcome;Peptide Hydrolases;Permeability;Pharmacodynamics;pharmacologic;Pilot Projects;Porifera;Pregnancy;Pregnancy in Adolescence;pregnancy prevention;Pregnancy Rate;prevent;Process;Prostate;Prostate-Specific Antigen;protein function;Proteins;prototype;Public Health;Reporting;reproductive tract;Research;Research Personnel;Resources;reversible contraceptive;Risk;screening;Seminal fluid;Seminal Plasma;Series;Serine Protease;Serine Proteinase Inhibitors;Site;small molecule;small molecule inhibitor;small molecule libraries;Specificity;sperm cell;sperm function;Sperm Motility;Sperm Transport;Spermatocidal Agents;statistics;System;Technology;Teenagers;Testing;three dimensional cell culture;Thrombin;Tight Junctions;Time;Tissues;Titrations;Toxic effect;translational approach;unintended pregnancy;United States;Unwanted pregnancy;Uterus;Vagina;Viscosity;Withdrawal;Woman;women's prevention;Work

PROJECT_TITLE: Disruption of semen liquefaction using specific KLK3 inhibitors as a new contraceptive

STUDY_SECTION: CMIR

STUDY_SECTION_NAME: Cellular, Molecular and Integrative Reproduction Study Section[CMIR]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Bioengineering

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: Project Narrative Changes in the elastic properties of connective tissue elements within muscle are associated with several neuromuscular disorders, aging, and occur secondarily to stroke and spinal cord injury. A fundamental understanding of the influence of these elements on muscle mechanical function will inform the design of rehabilitative strategies and interventions to improve muscle-tendon function. An improved understanding of how both muscle fluid mechanics and elastic elements influence the mechanical behavior of healthy muscle-tendon units may also aid in the design of prosthetic devices.

PI_NAMEs: AZIZI, EMANUEL ;ROBERTS, THOMAS JAY (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: 3-Dimensional;aged;Aging;Animals;Architecture;attenuation;Behavior;Biological Models;Cerebral Palsy;Connective Tissue;Contracts;design;Diagnosis;Elasticity;Elements;experimental study;Extracellular Matrix;Fascia;Fiber;Fibrosis;Gait;Goals;improved;In Situ;Intervention;Intramuscular;Left;Length;Link;Liquid substance;Locomotion;Measurement;mechanical behavior;Mechanics;Modeling;Movement;Muscle;Muscle function;muscle stiffness;Neuromuscular Diseases;novel;Output;Pathologic;Pathology;Pathway interactions;Performance;physical model;pressure;Prevention;Process;Production;Property;Prosthesis;Prosthesis Design;Rattus;Recovery;Rehabilitation therapy;Sarcomeres;scale up;Secondary to;Shapes;Skin;Speed;Spinal cord injury;Stroke;Structure;Structure-Activity Relationship;System;Tendon structure;Testing;transmission process;Variant;Work

PROJECT_TITLE: Elastic mechanisms in locomotion

STUDY_SECTION: MRS

STUDY_SECTION_NAME: Musculoskeletal Rehabilitation Sciences Study Section[MRS]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

ORG_CITY: MINNEAPOLIS

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: PROJECT NARRATIVE Translational models for understanding human brain function in health a disease need translational tools that bridge the modality gap between many existing invasive and noninvasive techniques. \/\/hole brain directional functional connectivity as obtained from layer specific functional magnetic resonance imaging is such a tool gaining increased versatility in human research. Here we develop, validate and apply the required tools to perform these measurements non invasively in the non human primate model at unprecedented magnetic field strength.

PI_NAMEs: ZIMMERMANN, JAN  (contact)

PROGRAM_OFFICER_NAME: WANG, SHUMIN

PROJECT_TERMS: Address;Anatomy;Anesthesia procedures;Animal Model;Automobile Driving;awake;Axon;bone;Bone structure;Brain;Brain region;brain volume;Chronic;cognitive process;Communication;connectome;Custom;Databases;design;Development;Devices;Disease;Environment;experimental study;Feedback;Foundations;Functional Magnetic Resonance Imaging;Future;Goals;Head;Health;high resolution imaging;Human;human model;Image;Implant;in vivo;information processing;innovation;Investigation;Macaca;magnetic field;Magnetic Resonance;Magnetic Resonance Imaging;Maps;Measurement;Measures;Mental disorders;Methods;miniaturize;Modality;Modeling;Monkeys;neuroimaging;Neurons;Neurosciences;next generation;Noise;nonhuman primate;novel;Operative Surgical Procedures;Pattern;Performance;Physiological;Positioning Attribute;radio frequency;Reproducibility;Research;Resolution;response;Rest;Rodent;sample fixation;Signal Transduction;Solid;Structure;Support System;System;Techniques;Testing;Thick;Time;tool;Tracer;Translating;translational model;Translational Research;transmission process;ultra high resolution;Validation

PROJECT_TITLE: Connectome style neuroimaging in non human primates via novel integrated RF platforms

STUDY_SECTION: EITN

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


NIH_SPENDING_CATS: Autoimmune Disease;Bioengineering;Biotechnology;Clinical Research;Diabetes;Gene Therapy;Genetics;Immunotherapy;Pediatric

ORG_CITY: SEATTLE

ORG_NAME: BENAROYA RESEARCH INST AT VIRGINIA MASON

ORG_STATE: WA

PHR: Narrative The proposed studies are focused on engineering an immune cell product for the treatment and prevention of type 1 diabetes, an autoimmune disease affecting 1.25 million children and adults in the USA. This cell product will be designed to target the pancreatic islet and act locally to suppress inflammation and beta cell stress. The proposed work will advance our understanding of how to target therapies to the pancreas in type 1 diabetes.

PI_NAMEs: BUCKNER, JANE HOYT (contact);RAWLINGS, DAVID J

PROGRAM_OFFICER_NAME: BLONDEL, OLIVIER

PROJECT_TERMS: Address;Adult;Affect;Antigen Presentation;antigen test;Antigens;Autoimmune Diseases;autoimmune pathogenesis;Autoimmune Responses;Autoimmunity;Beta Cell;biological adaptation to stress;CD4 Positive T Lymphocytes;CD8B1 gene;cell growth;cell injury;Cell Physiology;Cell Survival;Cells;Cellular Stress;Child;Clinical;constitutive expression;Cytoprotection;deamidation;design;Disease;draining lymph node;effector T cell;Elements;endoplasmic reticulum stress;Engineered Gene;engineered T cells;Engineering;Environment;FOXP3 gene;Functional disorder;Genes;Goals;Health;Home;Homing;Human;Hyperglycemia;Immune Targeting;immunoengineering;Immunosuppression;Inflammation;Inflammatory;Insulin;Insulin-Dependent Diabetes Mellitus;Intervention;islet;islet cell antibody;Islets of Langerhans;Knowledge;knowledge integration;lentivirally transduced;Measures;Mediating;mouse model;neoantigens;novel;Organ;Pancreas;peripheral blood;Prevention;Recovery;Regulatory T-Lymphocyte;repaired;Research Personnel;Risk;Signal Transduction;Site;Specificity;Stress;Suppressor-Effector T-Lymphocytes;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;targeted delivery;targeted treatment;Testing;Therapeutic;therapeutic protein;Time;tissue injury;tissue repair;Work

PROJECT_TITLE: Harnessing engineered T regulatory cells to promote beta cell health in T1D


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Mental Illness;Neurosciences;Social Determinants of Health

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC

PHR: We propose to study the neuronal mechanisms underlying impaired contextual discrimination, which is an endophenotype of mood and anxiety disorders. Specifically, we will attempt to demonstrate that pattern separation is likely the neural mechanism underlying contextual discrimination. In addition, our results may suggest that strategies aimed at modulating hippocampal activity either by stimulating neurogenesis or by inhibiting the activity of mature granule cells will have potential therapeutic benefits for decreasing the contextual discrimination deficits that often accompany mood and anxiety disorders.

PI_NAMEs: HEN, RENE  (contact)

PROGRAM_OFFICER_NAME: HUPALO, SOFIYA

PROJECT_TERMS: Adult;adult neurogenesis;antagonist;antidepressant effect;Anxiety Disorders;B-Lymphocytes;Behavior;Behavioral;Brain region;Calcium;Cells;dentate gyrus;Development;Discrimination;Discrimination Learning;discrimination task;early life stress;endophenotype;Exercise;experience;experimental study;Exposure to;Freezing;Fright;Gene Expression;Grant;granule cell;Hippocampus;Hyperactivity;Image;Impaired cognition;Impairment;improved;Learning;Light;Maps;Measures;Mediating;Microscope;Mood Disorders;Mus;Negative Valence;neural;neurogenesis;neuromechanism;Neurons;Opsin;optogenetics;Pattern;Pharmaceutical Preparations;pharmacologic;Physiological;Population;Post-Traumatic Stress Disorders;Process;Publishing;Research;System;Testing;Therapeutic;Time;young adult

PROJECT_TITLE: Circuits underlying overgeneralization

STUDY_SECTION: PMDA

STUDY_SECTION_NAME: Pathophysiological Basis of Mental Disorders and Addictions Study Section[PMDA]


NIH_SPENDING_CATS: Aging;Atherosclerosis;Biotechnology;Cardiovascular;Endocrine Disruptors;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Human Genome;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: DETROIT

ORG_DEPT: PEDIATRICS

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: Project Narrative  Cardiovascular disease accounts for nearly 1 of every 3 deaths in the US, an average of 1 death every 38 seconds. The purpose of this project is to use functional genomic assays and novel statistical and computa- tional methods to identify common genetic factors that interact with BPA and phthalates exposure and provide a molecular mechanism for inter-individual variation in endothelial function and cardiovascular health.

PI_NAMEs: LUCA, FRANCESCA  (contact);PIQUE-REGI, ROGER ;WEN, XIAOQUAN

PROGRAM_OFFICER_NAME: DZIERLENGA, ANIKA LIN

PROJECT_TERMS: Accounting;Affect;African American;African American population;Alleles;American;American Heart Association;ATAC-seq;Atherosclerosis;atherosclerosis risk;Binding;Biological Assay;bisphenol A;Blood Vessels;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;Cardiovascular Manifestation;cardiovascular risk factor;Cardiovascular system;Catalogs;Cause of Death;Cell Death;cell type;Cells;Cessation of life;Chemicals;Chromatin;Chromosome Mapping;Clinical;Communities;Computing Methodologies;Coronary Arteriosclerosis;Cosmetics;Data;Development;DNA Library;Electrophoretic Mobility Shift Assay;Endocrine Disruptors;Endothelial Cells;endothelial dysfunction;Endothelium;Environmental Risk Factor;European;Exposure to;functional genomics;gene environment interaction;Gene Expression;Gene Expression Profiling;Gene Expression Regulation;General Population;Genes;Genetic;genetic approach;genetic architecture;genetic risk factor;Genetic Transcription;genetic variant;genome wide association study;Genomic approach;Heart Diseases;Heavy Metals;high risk;hormonal signals;In Vitro;Individual;Individual Differences;inter-individual variation;machine learning method;Maps;Measures;Mediating;men;Methods;Molecular;novel;Nucleotides;Outcome;Pathway interactions;Phenotype;phthalates;Play;pollutant;Population Group;Quantitative Trait Loci;Regulatory Element;Reporter;Reporting;response;risk variant;Role;Sampling;Signal Transduction;Smooth Muscle Myocytes;Statistical Methods;Stroke;System;Testing;transcription factor;transcriptome sequencing;Transfection;Validation;Variant;Vascular Endothelium;Visualization;web site;Woman

PROJECT_TITLE: Functional genomics of GxE in cardiovascular disease: BPA, phthalates and their interactions with gene regulation


NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: Branford

ORG_NAME: ABBRATECH, INC.

ORG_STATE: CT

PHR: NARRATIVE Improved methods for deriving high quality affinity reagents will be needed to keep up with the pending impact when single molecule protein sequencing instrumentation comes ‘online’ in the next few years. When that time comes, it is not a realistic expectation to be able to go to an existing Ab catalog for mAbs that are well-validated, cloned, and sequenced, and that work in specific applications against newly discovered biomarkers. The high costs and low throughput of current antibody-generating technologies represent significant roadblocks to the development of a comprehensive and broadly available resource of renewable affinity reagents. Thus, there is an urgent need for all Abs to be defined by their sequences and made recombinant.

PI_NAMEs: WEINER, MICHAEL P (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Advocate;Affinity;Antibodies;Area;Back;Bacteriophages;Binding;Biological Markers;biophysical analysis;biophysical properties;Biophysics;Biotechnology;Capital;Capital Financing;Catalogs;Cells;commercialization;Consumption;cost;Cost Savings;Data;Development;Directed Molecular Evolution;Employment;Engineering;Enzyme-Linked Immunosorbent Assay;Epitopes;Escherichia coli;expectation;experience;Failure;falls;Flow Cytometry;Future;Generations;Genes;Genetic Recombination;Immunization Schedule;Immunoglobulin G;improved;innovation;instrumentation;Integrase;Kinetics;Libraries;Measurement;Measures;Methods;Molecular Biology;Monoclonal Antibodies;Pain;Peptide Sequence Determination;Phage Display;Phase;Plasmids;pressure;Principal Investigator;Production;promoter;Protein Engineering;protein expression;Proteins;Publications;Publishing;Qualifying;Reagent;Recombinants;Resources;Risk;Robotics;scale up;screening;single molecule;Site;Specificity;Surface;System;Systems Integration;T-Cell Receptor;Technology;technology validation;Testing;Time;timeline;tool;Validation;vector;Work;Yeasts

PROJECT_TITLE: Platform for the High Throughput Generation and Validation of Affinity Reagents


NIH_SPENDING_CATS: Bioengineering;Brain Cancer;Brain Disorders;Cancer;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Radiation Oncology;Rare Diseases

ORG_CITY: SALT LAKE CITY

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Approximately 4,300 children in the US are diagnosed with brain tumors every year and, even when successful, available treatment options decrease quality of life, are costly, and pose significant risks for late effects. The proposed study aims to determine if a clinically available, FDA approved transcranial focused ultrasound system could perform histotripsy, a non-thermal therapy for tissue destruction, and serve as a widely translatable, non-invasive method for treating pediatric brain tumors.

PI_NAMEs: ODEEN, HENRIK CARL AXEL (contact)

PROGRAM_OFFICER_NAME: KING, RANDY LEE

PROJECT_TERMS: Ablation;Acceleration;Acoustics;Adoption;Amplifiers;Animals;attenuation;Benign;Brain;Brain Neoplasms;Cancer Etiology;Cells;Cephalic;chemotherapy;Child;Childhood;Childhood Brain Neoplasm;Childhood Malignant Brain Tumor;Clinical;Clinical Research;clinical translation;cost;cranium;design;Development;Diagnosis;Emerging Technologies;Experimental Designs;experimental study;Family suidae;FDA approved;Focused Ultrasound;Gases;Goals;Grant;heart damage;Heating;high risk;Human;in vivo;innovation;Late Effects;Lesion;Literature;lung injury;Mechanics;Mediating;Methods;millisecond;Modality;Modeling;Morbidity - disease rate;mortality;National Institute of Biomedical Imaging and Bioengineering;Nervous System Disorder;neuro-oncology;Neurologic;novel;Operative Surgical Procedures;Outcome;pediatric patients;Physiologic pulse;Play;Population;pressure;Process;Quality of life;Radiation exposure;Radiation therapy;Research;Research Personnel;response;Risk;Safety;Scalp structure;Second Primary Cancers;Series;Shapes;Shock;simulation;Stress;System;Tadpoles;Testing;Therapeutic;Thermal Ablation Therapy;Tissue Therapy;Tissues;Transducers;transmission process;Tremor;Ultrasonic Transducer;Ultrasonics

PROJECT_TITLE: Feasibility of transcranial histotripsy for pediatric neuro-oncology applications using a hemispherical transducer


ORG_CITY: ANN ARBOR

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE When blood clots form in the large veins, a common condition known as deep vein thrombosis (DVT), patients are treated with blood thinning medications, which carry the risk of bleeding and are ineffective at dissolving the clot, ultimately leading to the risk of recurrent DVT and chronic leg swelling, pain and ulcers (post thrombotic syndrome). Immune cells (monocytes/macrophages) help to break down the thrombus, and accelerate this process without bleeding risk. This research proposal is intended to evaluate the role of a common cellular signaling pathway, TLR4, in monocytes/macrophages in directing thrombus resolution, assess potential as a therapeutic strategy, and provide advanced immunologic training for a promising young surgeon-scientist.

PI_NAMEs: OBI, ANDREA TARA (contact)

PROGRAM_OFFICER_NAME: YABE, IDALIA MONTANO

PROJECT_TERMS: Acceleration;Acquired Immunodeficiency Syndrome;Acute;Address;Anticoagulants;Biology;Blood coagulation;Blood Vessels;Bone Marrow;career;Caring;Cells;Cessation of life;Chromatin;Chronic;chronic thromboembolic pulmonary hypertension;Clinic;Clinical;clinical care;Coagulation Process;cytokine;Cytokine Gene;Data;Data Analyses;deep field survey;Deep Vein Thrombosis;Development;Ensure;Enzymes;Epigenetic Process;epigenetic regulation;experience;Fellowship;Foundations;Functional disorder;Funding;Gene Expression;Goals;Health;Hemorrhage;histone methyltransferase;Human;IL6 gene;Immune;Immunologics;Immunology;immunothrombosis;improved;Inflammatory;Injury;Innate Immune Response;Innate Immune System;innovation;insight;Kinetics;Knowledge;Knowledge acquisition;Leg;Leukocytes;Life;Ligands;Limb structure;Macrophage;Malignant Breast Neoplasm;Mediating;Mediator;Mentorship;Methylation;Microbiology;Microsurgery;Mixed-Lineage Leukemia;Modeling;Modernization;Modification;Molecular;Molecular Target;monocyte;Morbidity - disease rate;mouse model;Mus;Myelogenous;Natural Immunity;Operative Surgical Procedures;Pain;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;pharmacologic;Play;Postdoctoral Fellow;Postphlebitic Syndrome;Process;Production;Program Development;programs;Pulmonary Embolism;Recurrence;Research;Research Design;Research Proposals;Residual state;Resolution;response;Risk;Role;Scientist;Signal Pathway;Signal Transduction;skills;Source;stem cells;success;Surgeon;Swelling;Talents;Techniques;Testing;Therapeutic;Thrombolytic Therapy;Thrombosis;thrombotic;Thrombus;Time;TLR4 gene;Training;Training Programs;Translating;Ulcer;undergraduate education;United States;Up-Regulation;Veins;Venous;Venous Thrombosis

PROJECT_TITLE: Myeloid TLR4 epigenetic regulation and signaling in accelerating venous thrombus resolution


NIH_SPENDING_CATS: Asthma;Health Effects of Indoor Air Pollution;Lung;Prevention

ORG_CITY: SCOTTSDALE

ORG_NAME: MAYO CLINIC ARIZONA

PHR: PROJECT NARRATIVE  The prevalence of allergic diseases is increasing worldwide. The long-term objective of this project is to investigate the fundamental mechanisms underlying the etiology of these immune-mediated diseases. Specifically, we will investigate how exposure of airway epithelium to environmental allergens initiates the immune responses that culminate in the disease process underlying allergic inflammation. Successful completion of this project will provide new prevention and treatment strategies for these diseases.

PI_NAMEs: KITA, HIROHITO  (contact);O'GRADY, SCOTT M.

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: Acetylcholine;Address;airborne allergen;Airway Disease;airway epithelium;Allergens;Allergic;allergic airway inflammation;Allergic Disease;Allergic inflammation;Alternaria;Animal Model;Asthma;autocrine;Binding;Biochemistry;bronchial epithelium;Calcium;Cell Nucleus;Cell Physiology;Cell secretion;Cells;Cellular biology;Cholinergic Receptors;chronic rhinosinusitis;Collaborations;cytokine;Data;Development;Disease;environmental allergen;Environmental Exposure;Environmental Risk Factor;Epithelial Cells;Epithelium;Etiology;Event;experimental study;exposed human population;Exposure to;extracellular;Family;Functional disorder;Funding;genetic regulatory protein;Genome;genome wide association study;House Dust Mite Allergens;Human;human disease;Immune;Immune response;Immunity;Immunologics;Immunology;immunopathology;In Vitro;in vivo;in vivo Model;Interleukin-1;Knowledge;Laboratories;Link;Literature;Lung;Mediating;Modeling;Molecular;Molecular Biology;mouse model;Mucous Membrane;Muscarinic M3 Receptor;new therapeutic target;novel;Nuclear;Oxidative Stress Induction;Pathologic;Pharmacology;Phosphorylation;Physiology;Play;Prevalence;prevent;Prevention strategy;Principal Investigator;Process;Production;protein activation;Protein Kinase C;Proteins;receptor;Receptor Signaling;response;Role;Shapes;Signal Pathway;Signaling Protein;Single Nucleotide Polymorphism;Skin;Testing;treatment strategy;TSLP gene

PROJECT_TITLE: Mechanisms of IL-33 secretion in allergic diseases

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIB-E(57)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE We expect the results of this work will inform on a mechanism for defective rewiring in brain connectivity, and dysfunction of large subsets of neuronal proteins and their networks, by the so-called epichaperome, a maladaptive regulator of proteostasis. These are hypothesis-driven and clinically relevant studies into Alzheimer's disease that also provide insights into new aspects of Alzheimer's disease biology.

PI_NAMEs: ARANCIO, OTTAVIO ;CHIOSIS, GABRIELA  (contact)

PROGRAM_OFFICER_NAME: PETANCESKA, SUZANA

PROJECT_TERMS: abeta oligomer;Address;Affect;age related;Alzheimer's Disease;Alzheimer's disease model;Amyloid beta-Protein;Biology;Brain;Cell model;Cells;Chemicals;Chronic;clinically relevant;Cognition;Cognitive deficits;cognitive function;Communication;Complex;Data;Defect;Deterioration;Disease;Equilibrium;Exhibits;experimental study;Exposure to;flexibility;Functional disorder;Gene Modified;Global Change;Goals;Heat-Shock Proteins 90;Hippocampus;Human;human induced pluripotent stem cells;Image;Impairment;In Vitro;in vivo;Individual;induced pluripotent stem cell;insight;Investigation;Kinetics;Knock-in Mouse;Knock-out;Knockout Mice;Laboratories;Lead;Learning;Link;Long-Term Potentiation;Mediating;Memorial Sloan-Kettering Cancer Center;Memory;Memory impairment;Memory Loss;Modeling;Molecular;Molecular Chaperones;mouse model;Mus;Mutation;Nature;neuronal circuitry;Neurons;Non-Invasive Detection;Organ;Outcome;Pathologic;Pathway interactions;Patients;Phase;Phenotype;Physiological;protein folding;protein protein interaction;Proteins;Proteome;proteostasis;Publishing;research clinical testing;response;Role;scaffold;Set protein;small molecule;Stem Cell Research;Stress;stressor;Structure;Swedish mutation;Synapses;synaptic failure;synaptic function;Synaptic plasticity;tau aggregation;tau expression;tau Proteins;Testing;Therapeutic;translational applications;Translational Research;Validation;Work

PROJECT_TITLE: Chaperome networks in Alzheimer's disease

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer

ORG_DEPT: PHARMACOLOGY

PHR: Project Narrative This project merges the expertise and knowledge of its academic and industrial partners to develop and deploy novel drug discovery technology for identifying allosteric kinase inhibitors with primary applicability in oncology. Allosteric kinase inhibitors represent exciting next-generation cancer therapeutics that circumvent many of the limitations of current ATP-competitive kinase inhibitors.

PI_NAMEs: LEVINSON, NICHOLAS MARK (contact);THOMAS, DAVID D

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Acceleration;Adoption;Affinity;Basic Science;Binding;Biochemical;Biological Assay;Biophysics;Biosensor;c-myc Genes;Cancer cell line;Cancer Patient;Chemicals;Classification;Clinical;Complex;Couples;crizotinib;Detection;Development;Disease;Dissociation;drug development;drug discovery;Exons;FDA approved;field study;Fluorescence;Fluorescence Resonance Energy Transfer;follow-up;high throughput screening;Industrialization;industry partner;inhibitor;innovation;instrumentation;kinase inhibitor;Knowledge;Libraries;Ligands;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;MET gene;Minnesota;Mission;Molecular Conformation;Monitor;Movement;Mutation;nanosecond;next generation;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Oncology;Oncoproteins;Patients;Phosphotransferases;photonics;prevent;programs;Proto-Oncogene Proteins c-myc;Reader;Receptor Protein-Tyrosine Kinases;Regulatory Element;Research;Resistance;Resistance development;resistance mutation;scaffold;sensor;sensor technology;Site;small molecule;success;Technology;technology development;Testing;Therapeutic;therapeutic target;Translating;treatment strategy;tumor;tumorigenesis;Ubiquitination;Universities;Validation

PROJECT_TITLE: A transformative drug discovery platform for allosteric kinase inhibitors


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: GAINESVILLE

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative We have developed an innovative new enzyme-based therapeutic technology to shut down inflammation. As an injectable into the bloodstream, this new type of drug is showing great promise for the treatment of liver ischemia-reperfusion injury, which is a major clinical problem lacking treatment options.

PI_NAMEs: KESELOWSKY, BENJAMIN GEORGE (contact);ZARRINPAR, ALI

PROGRAM_OFFICER_NAME: SHERKER, AVERELL H

PROJECT_TERMS: Acute;Address;Anti-Inflammatory Agents;Antibodies;Antigens;Automobile Driving;Biological;Blood Circulation;Blood flow;Catalogs;Cell Death;cell injury;Cell Physiology;cell type;Cells;Chronic;Circulation;Clinical;clinical practice;Coupled;cytotoxicity;Data;Disease;Dose;drug action;Drug Kinetics;druggable target;Engraftment;Enzymes;Essential Amino Acids;extracellular;Formulation;Future;Goals;Half-Life;Homeostasis;Immune;Immune response;Immunocompromised Host;immunogenicity;Immunophenotyping;immunoregulation;Immunosuppression;implantation;In Vitro;in vivo;Incidence;Inflammation;Inflammatory;Injectable;Injections;Injury;innovation;interest;intravenous administration;Ischemia;Kynurenine;Left;Liquid substance;Liver;Liver Dysfunction;Liver Failure;liver ischemia;Maximum Tolerated Dose;Mediator;Metabolic;Metabolism;Myocardial Infarction;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;Organ;Organ failure;Outcome;Pathology;Pathway interactions;Pharmaceutical Preparations;Pharmacodynamics;Polyethylene Glycols;Positioning Attribute;preconditioning;preservation;Process;programs;prophylactic;Reperfusion Injury;restoration;side effect;Site;Sterility;Stroke;success;systemic toxicity;Technology;Therapeutic;tissue repair;Tissues;Toxic effect;Toxicology;Transplantation;Trauma;Tryptophan;Tryptophan 2,3 Dioxygenase;Tryptophan Metabolism Pathway;Vascular blood supply

PROJECT_TITLE: Directing Tryptophan Immunometabolism to Ameliorate Liver Ischemic-Reperfusion Injury

STUDY_SECTION: GDD

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Lymphatic Research;Urologic Diseases

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Studying chimeric RNAs and their involvement in lymph node metastasis of bladder cancer may uncover new mechanisms that drives bladder cancer progression. Chimeras identified through the study may be developed into diagnostic/prognostic markers and/or therapeutic targets.

PI_NAMEs: LI, HUI  (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: Address;Affect;analysis pipeline;Animal Model;Area;Basic Science;bioinformatics pipeline;Biological Markers;cancer cell;cancer diagnosis;Cancer Patient;cancer type;Categories;Cause of Death;Cells;Cessation of life;chemotherapy;Chemotherapy and/or radiation;Chimera organism;Chimeric Proteins;China;Chinese;Chromosomal Rearrangement;Clinical;Code;Collaborations;Collection;Country;Data;Databases;Death Rate;Deposition;Diagnostic;diagnostic biomarker;differential expression;Disease;Disease Progression;DNA;driver mutation;epigenomics;epitranscriptomics;FGFR3 gene;Fingerprint;Funding;Gender;Gene Fusion;gene product;Genes;genome sequencing;Genomics;Genotype-Tissue Expression Project;Immunotherapy;improved;large datasets;lymph nodes;Lymphatic;Lymphatic Metastasis;Malignant neoplasm of cervix uteri;Malignant neoplasm of prostate;Malignant neoplasm of urinary bladder;Malignant Neoplasms;men;Metastatic Neoplasm to Lymph Nodes;Modeling;Molecular;Multiomic Data;nanoparticle delivery;Neoplasm Metastasis;Neoplasms;novel;novel diagnostics;novel therapeutic intervention;Online Systems;Operative Surgical Procedures;Paper;patient prognosis;Patients;Positive Lymph Node;Process;Prognosis;Prognostic Factor;Prognostic Marker;Proteins;Proteomics;Publishing;Recurrence;Reporting;Resources;RNA;RNA Splicing;Role;Sampling;sequencing platform;Side;siRNA delivery;Somatic Mutation;success;TACC3 gene;The Cancer Genome Atlas;Therapeutic;therapeutic target;Third Generation Sequencing;Trans-Splicing;Transcript;transcriptome sequencing;transcriptomics;tumor;tumor progression;tumorigenic;Untranslated RNA;whole genome;Work

PROJECT_TITLE: Chimeric RNAs and their implication in lymphatic metastasis of bladder cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-N(50)R]


NIH_SPENDING_CATS: American Indian or Alaska Native;Behavioral and Social Science;Brain Disorders;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Depression;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Nutrition;Obesity;Pediatric;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative The goal of this research is to evaluate the impact of a culturally tailored, intergenerational, home-based type 2 diabetes intervention for American Indian adult diabetes-related health outcomes including HbA1c. We will also evaluate the impact of the program on enrolled adult's children in terms of diabetes risk and protective factors. If the intervention is effective, American Indian communities may benefit from an empirically supported, family-based model with promise to break the cycles of intergenerational diabetes.

PI_NAMEs: WALLS, MELISSA L. (contact)

PROGRAM_OFFICER_NAME: RAJAPAKSE, NISHADI

PROJECT_TERMS: Acceleration;Address;Adult;Age;aged;American Indian community;American Indian Population;American Indians;Behavior;Behavioral;behavioral health;Blood Pressure;Body mass index;Buffers;Caregivers;Child;Chippewa;Chronic Disease;Collaborations;commune;Communities;community based participatory research;community involvement;Community Participation;comparison control;coping;coping mechanism;Coping Skills;Data;depressive symptoms;design;diabetes management;Diabetes Mellitus;Diabetes prevention;diabetes risk;Diagnosis;dietary adherence;Disparity;Educational Curriculum;Educational process of instructing;effectiveness evaluation;Effectiveness of Interventions;Elements;empowerment;Enrollment;Epidemic;Ethnic Population;Evaluation;experience;Family;Family health status;family support;follow-up;Foundations;Fracture;Generations;Glycosylated hemoglobin A;Goals;good diet;Grant;Health;health disparity;health equity;Health Personnel;Healthcare Systems;Healthy Eating;Home;Human;improved;Intake;intergenerational;Intervention;intervention effect;intervention participants;Knowledge;Life;Life Style;Lipids;Maps;Measures;Mediating;Mental Depression;Mental Health;Midwestern United States;Modeling;Morbidity - disease rate;mortality;Motivation;Non-Insulin-Dependent Diabetes Mellitus;novel;nutrition;Outcome;Parents;Pattern;Pharmaceutical Preparations;Physical activity;physical conditioning;Physiological;Pilot Projects;prevent;Prevention;preventive intervention;primary outcome;Process;Program Effectiveness;programs;protective factors;Psyche structure;psychosocial;Qualitative Evaluations;racial population;Randomized;randomized, controlled study;Randomized, Controlled Trials;Research;Resources;response;Risk Factors;Role;Services;skills;Stress and Coping;stress management;stressor;sugar;support network;sweetened beverage;Techniques;therapy design;Trauma;tribal community;tribal health;Waiting Lists;Work;Youth

PROJECT_TITLE: Family-Based, Culturally-Centered Diabetes Intervention with Ojibwe Communities

STUDY_SECTION: PRDP

STUDY_SECTION_NAME: Psychosocial Risk and Disease Prevention Study Section[PRDP]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Genetics;Lung;Rare Diseases;Regenerative Medicine

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Repair and regeneration of the lung alveoli are essential to restore the ability of gas exchange after lung injury. The molecular pathways that drive this process are poorly understood. The current proposal seeks to characterize a newly identified epigenetic and potentially druggable process that regulates how cells differentiate and reprogram from one state to another.

PI_NAMEs: MORRISEY, EDWARD E (contact)

PROGRAM_OFFICER_NAME: LIN, SARA

PROJECT_TERMS: Acceleration;Acute;Acute Lung Injury;Address;Aging;Alleles;Alveolar;alveolar epithelium;Alveolus;Biological Assay;cell behavior;Cell Differentiation process;Cell division;Cell Reprogramming;Cells;ChIP-seq;Chronic Disease;conditional knockout;Data;derepression;Development;DNA Methylation;Dose;Endoderm;Enzymes;Epigenetic Process;Functional Regeneration;Gases;Gene Expression;Genes;Genetic Markers;Genetic Transcription;histone modification;Homeostasis;Hyperoxia;improved;in vivo regeneration;Infectious Agent;inhibitor;Injury;Innate Immune Response;Knockout Mice;Laboratories;Lead;Lung;lung development;lung injury;lung regeneration;Metabolic;Metabolism;Methylation;MicroRNAs;Modeling;Molecular;Mus;mutant;Natural regeneration;Organoids;Oxidative Phosphorylation;Pathway interactions;Play;Pluripotent Stem Cells;pollutant;premature;Process;programs;Proliferating;Pulmonary alveolar structure;pulmonary function;regenerative;repaired;Research;Respiratory System;response;response to injury;Rest;Role;Sentinel;Signal Transduction;single-cell RNA sequencing;small molecule;Somatotype;stem cell population;Stimulus;surfactant production;telomere;tissue regeneration;Tissues;Untranslated RNA

PROJECT_TITLE: Control of lung alveolar regeneration by Dot1L/H3K79 methylation

STUDY_SECTION: LIRR

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


NIH_SPENDING_CATS: Genetics;Infectious Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Transplantation

ORG_CITY: TUCSON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

PHR: PROJECT NARRATIVE The goal of our Program is to elucidate the molecular mechanisms by which human cytomegalovirus regulates molecular signaling in the host to establish latency and reactivate. Despite advances in diagnostics and therapeutics, HCMV remains a major life-threatening complication following solid organ or stem cell transplantation. Our projects will define a network of virus-host interactions that will inform antiviral strategies to control HCMV latency and reactivation.

PI_NAMEs: GOODRUM, FELICIA D (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Address;Amino Acids;attenuation;Biology;CD34 gene;cell type;Cells;Cercopithecine Herpesvirus 1;cofactor;collaborative approach;Complex;Complication;Cytomegalovirus;Cytomegalovirus Infections;Data;Defective Viruses;Dependence;Diagnostic;Disease;DNA biosynthesis;DNA Damage;Endothelial Cells;Epidermal Growth Factor Receptor;Genes;Genome;Goals;Growth;Hematopoietic;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Human;humanized mouse;immunodeficiency;Immunoprecipitation;In Vitro;in vitro Model;in vivo;in vivo Model;Individual;Infection;insight;Integration Host Factors;Interferons;knock-down;latent infection;Life;Maintenance;Maps;Mass Spectrum Analysis;Mediating;MEKs;Molecular;Morbidity - disease rate;mortality;mouse model;mutant;novel;novel virus;Organ;organ transplant recipient;Pathway interactions;PI3K/AKT;Positioning Attribute;prevent;programs;protein transport;Proteins;Proto-Oncogene Proteins c-akt;reactivation from latency;recombinant virus;Regulation;Reporting;Research;response;Role;scaffold;Signal Transduction;Solid;STAT1 gene;Stem cell transplant;stem cells;Stimulus;Switching Complex;Therapeutic;trafficking;Transcript;transcription factor;ubiquitin-specific protease;Undifferentiated;Viral;viral DNA;Viral Genes;Virus;virus host interaction;Virus Latency;Virus Replication;WD Repeat;Work

PROJECT_TITLE: Virus-host interactions regulating innate signaling for human cytomegalovirus latency

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIA-B(02)]


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

PHR: Project Narrative: Continuous Evolution of Proteins with Novel Therapeutic Potential We have successfully evolved many different classes of proteins with new and altered activities using a technology that we developed to evolve biomolecules ≥100-fold faster than conventional laboratory evolution approaches. We propose to use this technology to evolve novel proteins with therapeutic potential, or that serve as new tools for therapeutics discovery. Success would enable the development of next-generation therapeutic agents to treat human diseases including genetic and neurodegenerative disorders.

PI_NAMEs: LIU, DAVID R (contact)

PROGRAM_OFFICER_NAME: CHEN, JERMONT

PROJECT_TERMS: Age;Agriculture;Alleles;Animal Model;Antibodies;Bacteriophages;base editor;Binding Proteins;Biological Process;Biological Sciences;Biotechnology;Brain Diseases;Cell model;Cells;Clinical;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Development;Disease;disease-causing mutation;DNA;DNA-Directed RNA Polymerase;drug-sensitive;Enzymes;Escherichia coli;Evolution;Foundations;functional genomics;gene product;Genes;Genetic Diseases;genetic manipulation;Genome;genome editing;genomic tools;Goals;Guide RNA;Human;human disease;Human Genetics;in vivo;Infection;innovation;Insecticides;interest;Intervention;Laboratories;macromolecule;Malignant neoplasm of brain;Mediating;Methods;Modality;Mutagenesis;mutation correction;Neurodegenerative Disorders;new technology;next generation;novel;novel therapeutics;nuclease;Peptide Hydrolases;Pharmaceutical Preparations;Plants;Plasmids;prime editing;prime editor;programs;Property;protein degradation;protein E;Proteins;Proteome;Research;Research Personnel;research study;RNA;Science;small molecule;Specificity;success;System;Technology;Therapeutic;Therapeutic Agents;therapeutic development;therapeutic target;Time;tool;Variant

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 including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Dementia;Genetics;Human Genome;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PHR: Project Narrative Alzheimer's disease (AD) is the leading cause of dementia and the sixth leading cause of death in the United States, while the current disease incidence indicates approximately 16 million Americans will be affected by 2050 without an effective treatment. This proposal will develop intelligent computer-based network medicine and systems pharmacology tools, capable of searching human genome sequencing findings and existing drug-target databases, while also testing the most promising network-predicted repurposable drugs and drug combinations using large-scale patient longitudinal data complemented by in vitro and in vivo mechanistic observations. The innovative network methodologies and potential prevention/therapeutic approaches developed in this proposal will prove to be novel and effective ways to improve outcomes in long-term dementia care and quality of life for the rapidly growing AD population.

PI_NAMEs: CHENG, FEIXIONG  (contact)

PROGRAM_OFFICER_NAME: ARUNKUMAR, NANDINI

PROJECT_TERMS: Acceleration;AD transgenic mice;Address;Adherence;Affect;Algorithms;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease therapy;American;Amyloid;Amyloidosis;Animal Model;Bayesian Modeling;bioinformatics tool;Biological Assay;Biological Availability;Blood - brain barrier anatomy;Brain;brain endothelial cell;brain tissue;Case/Control Studies;Cause of Death;Cells;Central Nervous System;clinical efficacy;Clinical Trials;clinically relevant;Combination Drug Therapy;Combined Modality Therapy;Complex;Computerized Medical Record;Computers;Data;Databases;Dementia;dementia care;Disease;Disease Outcome;Drug Combinations;Drug Delivery Systems;drug development;drug discovery;drug efficacy;drug repurposing;Drug Targeting;drug testing;Drug user;effective therapy;efficacious treatment;endophenotype;Enhancers;Evaluation;Foundations;functional genomics;Genes;genetic architecture;Genome;genome wide association study;genome-wide;genomic data;Heritability;Hi-C;Hippocampus;Human;Human Genetics;human genome sequencing;human interactome;improved outcome;in silico;In Situ;In Vitro;in vivo;Incidence;individual patient;informatics tool;innovation;Interdisciplinary Study;Investments;Knowledge;Late Onset Alzheimer Disease;Mediating;Medicine;Methodology;Microglia;Molecular;mouse model;Multiomic Data;multiple omics;Mutate;Network-based;Neurodegenerative Disorders;Neuroglia;novel;novel therapeutics;Pathogenesis;Patient Care;patient health information;Patients;Penetration;Pharmaceutical Preparations;Pharmacoepidemiology;pharmacokinetic model;pharmacologic;Pharmacologic Substance;Pharmacology;Pharmacotherapy;Physiological;Population;population based;Positioning Attribute;predictive tools;Predisposition;Prevention;Preventive therapy;promoter;Proteins;Proteome;Publications;Publishing;Quality of life;rational design;Rattus;Records;Regimen;research and development;Research Personnel;Resected;risk variant;Role;side effect;single cell sequencing;single-cell RNA sequencing;symptom treatment;System;tau Proteins;Tauopathies;Testing;Therapeutic;therapeutic development;tool;transcriptome;Transgenic Animals;transgenic model of alzheimer disease;trial design;United States;Validation;Visualization;web app;Work

PROJECT_TITLE: Endophenotype Network-based Approaches to Prediction and Population-based Validation of in Silico Drug Repurposing for Alzheimers Disease


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Congenital Heart Disease;Gene Therapy;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Pediatric;Rare Diseases

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Heart diseases remain leading causes of death in industrialized countries including the US. The overall goal of this project is to develop new gene therapies that employ engineered prokaryotic sodium and calcium channels. The ability of these therapies to improve electrical and mechanical function of the heart will be tested in mouse models of disease.

PI_NAMEs: BURSAC, NENAD  (contact)

PROGRAM_OFFICER_NAME: DARINGER, NICHOLE MARIE

PROJECT_TERMS: 3-Dimensional;Action Potentials;Address;adeno-associated viral vector;adeno-associated virus 9 delivery;Adult;Adverse effects;Animal Model;Anti-Arrhythmia Agents;Arrhythmia;biophysical properties;Brugada syndrome;Calcium;Calcium Channel;candidate identification;Cardiac;Cardiac Electrophysiologic Techniques;Cardiac Myocytes;cardiac tissue engineering;Cause of Death;Cell Culture Techniques;Cells;Chromosome Mapping;Codon Nucleotides;Computer Simulation;Congenital Abnormality;coronary fibrosis;Defect;Developed Countries;Disease;disease model;Echocardiography;Electrocardiogram;Electrophysiology (science);Engineering;extracellular;Fibrosis;Foundations;Functional disorder;Future;gene therapy;Genes;Genetic;Genetic Engineering;Goals;Heart;Heart Diseases;Heart failure;heart function;hemodynamics;Human;Human body;Human Engineering;Impairment;improved;in silico;In Situ;In Vitro;in vitro Model;in vivo;in vivo evaluation;Ions;Kinetics;Left;loss of function mutation;Loss of Heterozygosity;Mammalian Cell;Maps;Measurement;Mechanics;Mediating;Membrane;Methods;Modeling;mouse model;Mus;Muscle Contraction;Mutate;Mutation;Myocardial Infarction;Myocardial Ischemia;Myocardium;Neonatal;novel;Optics;Orthologous Gene;overexpression;patch clamp;Pathology;Permeability;pharmacologic;Play;Potassium Channel;Predisposition;Preparation;prevent;Property;Rattus;recombinant viral vector;Regulation;Role;Short QT syndrome;Sick Sinus Syndrome;Site-Directed Mutagenesis;Slice;Sodium;Sodium Channel;Speed;sudden cardiac death;Syndrome;System;Testing;Therapeutic;Therapeutic Effect;Tissue Model;Tissues;trafficking;transgene expression;Variant;Ventricular;Viral;Viral Vector;Virus;voltage;Work

PROJECT_TITLE: Engineered BacNav and BacCav for Improved Excitability and Contraction


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Orphan Drug;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: BRAFV600E-positive papillary thyroid cancers (PTC) correlate with metastasis and increased mortality and develop resistance to current treatments; accurate delineation of the critical factors in aggressive PTC is therefore urgently needed for early diagnosis and effective new therapies. Although the FDA has approved selective BRAFV600E inhibitors that showed promise in clinical trials, primary and secondary resistance to these inhibitors has been widely reported, and our studies of the impact of thrombospondin1 (TSP-1) on the PTC microenvironment and the CDK4/6-E2F1 pathway on genomic instability imply novel targetable mechanisms. We recently identified the first thyroid-specific long intergenic noncoding RNA (lincRNA), which is epigenetically silenced by BRAFV600E to deregulate iodine metabolism, promote tumor cell survival and resistance, but is rescued by a trimodal combination of anti-BRAFV600E-EZH2-CDK4/6 drug therapies for aggressive BRAFV600E-PTC; our analysis of this lincRNA’s mechanisms and regulation will have a significant translational impact on patient outcomes by identifying critical factors in PTC and supporting clinical trials of new, more accurately targeted combination therapies.

PI_NAMEs: NUCERA, CARMELO  (contact)

PROGRAM_OFFICER_NAME: KAI, MIHOKO

PROJECT_TERMS: 3-Dimensional;Affect;Anti-sense RNA;ATAC-seq;Binding Sites;Biology;cancer cell;Cancer Patient;CDK4 gene;Cell Death;Cell Proliferation;Cell Survival;Cells;ChIP-seq;Chromatin;Clinical;Clinical Trials;clinically significant;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Code;Combined Modality Therapy;Complex;Data;density;design;Disease Progression;DNA Binding;Down-Regulation;drug development;Drug resistance;E2F transcription factors;Early Diagnosis;efficacy evaluation;Enhancers;Enzymes;Epigenetic Process;epigenetic silencing;ERBB3 gene;Extracellular Matrix Proteins;EZH2 gene;FRAP1 gene;Genes;Genetic Transcription;Genomic Instability;Histone Acetylation;histone methylation;Histones;Human;Hydrogen Peroxide;In Vitro;in vivo;inhibitor;Invaded;Iodide Peroxidase;Iodine;Link;Malignant Neoplasms;Maps;Metabolism;Modality;mortality;mouse model;Mutation;Neoplasm Metastasis;neoplastic cell;Normal tissue morphology;novel;novel therapeutics;overexpression;Oxidative Stress;Papillary thyroid carcinoma;Paracrine Communication;Pathway interactions;Patient-Focused Outcomes;Pericytes;Pharmacotherapy;Play;Proliferating;promoter;radioiodine therapy;Recurrence;Regulation;Reporting;Resistance;Resistance development;restoration;RNA;Role;Sampling;screening;Secondary to;Signal Transduction;Survival Rate;synergism;targeted treatment;Technology;Therapeutic;Thrombospondin 1;Thrombospondins;Thyroid carcinoma;Thyroid Gland;Tissues;Transcription Repressor;transcriptome;transcriptome sequencing;Transforming Growth Factor beta;translational impact;tumor;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;Untranslated RNA;Up-Regulation;uptake;XCL1 gene

PROJECT_TITLE: Role of newly identified, thyroid-specific LincRNA in BRAFV600E thyroid carcinoma

STUDY_SECTION: MCE

STUDY_SECTION_NAME: Molecular and Cellular Endocrinology Study Section[MCE]


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

ORG_DEPT: NEUROLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative: This project focuses on generating two critical tools to characterize newly identified protein assemblies (termed “biomolecular condensates”) that regulate the function of microglia (brain-resident cleaning cells) in aging and Alzheimer Disease (AD). Specifically, we will develop and validate: i) a CRISPR engineered microglial cell line that allows us to monitor these condensates in living cells; and ii) novel workflows to identify additional protein components of these condensates. These tools, which will be shared with the field, will enable future work to understand how these condensates regulate microglial function - knowledge that will be pivotal in designing precision biomarkers and therapeutics to manage microglial dysfunction in aging and AD.

PI_NAMEs: ST GEORGE-HYSLOP, PETER HENRY (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: abeta oligomer;Actins;Address;Aging;Alzheimer's Disease;Antibodies;Antibody Affinity;Autopsy;Biological Assay;Biological Markers;Biology;Biophysics;BLNK gene;Brain;brain tissue;Cell Line;Cell model;cell type;Cells;Cellular biology;Characteristics;Client;Clustered Regularly Interspaced Short Palindromic Repeats;Cytoplasm;Cytoskeleton;Data;design;Disease;Engineering;Enzymes;Epitopes;Equipment and supply inventories;experimental study;Fluorescence Recovery After Photobleaching;Functional disorder;Future;Genes;Genetic study;Human;human induced pluripotent stem cells;Immunofluorescence Immunologic;In Situ;induced pluripotent stem cell;Investigation;Knowledge;Ligands;Ligation;Liquid substance;Location;Mass Spectrum Analysis;Mediating;Membrane;Microglia;migration;Molecular;Molecular Target;Monitor;Mutation;Nature;neurotransmission;novel;Nucleoplasm;Pathogenesis;Pathway interactions;Phagocytosis;Phase;Phase Transition;Phospho-Specific Antibodies;Physical condensation;Physiological;Play;PLCG2 gene;Post-Translational Protein Processing;potential biomarker;protein purification;Proteins;Proteomics;Protocols documentation;Reagent;receptor;resilience;Resources;response;Risk;Role;scaffold;Signal Pathway;Specificity;targeted biomarker;Testing;Therapeutic;therapeutic target;tool;TREM2 gene;TYROBP gene;Validation;Variant;Western Blotting;Work

PROJECT_TITLE: Critical tools enabling analysis of biomolecular condensates in microglial signaling and function in aging and Alzheimer Disease


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

ORG_STATE: MD

PHR: The proposed research will shed light on how reprogramming of the creatine metabolic pathway participates in breast cancer metastasis and help us to better understand key enzymes in creatine metabolism of breast cancer. Creatine metabolism holds promise as prognostic indicator and potential therapeutic target for metastatic breast cancer. We will develop integrated highly multiplexed mass spectrometry imaging and immunohistochemistry approaches to detect creatine metabolic enzymes and creatine metabolites in breast cancer specimens for future use in pathology workflows.

PI_NAMEs: GLUNDE, KRISTINE  (contact)

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: Adhesions;Affect;Amino Acids;Automobile Driving;Autopsy;Biopsy;Breast Cancer Cell;Breast Cancer cell line;breast cancer metastasis;Breast Cancer Model;cancer cell;cell behavior;Cell Line;Cells;Choline Kinase;Clinical;Collection;Creatine;Data;Distant Metastasis;Enzymes;epithelial to mesenchymal transition;experimental study;Freezing;Future;gain of function;Gene Expression;Generations;Genes;Glucose;Glutaminase;Glycolysis;Human;Image;Immunohistochemistry;in vivo magnetic resonance spectroscopy;Invaded;Knowledge;lactate dehydrogenase A;lipid metabolism;loss of function;lymph nodes;Magnetic Resonance Spectroscopy;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Maps;mass spectrometric imaging;Measures;Metabolic;Metabolic Pathway;Metabolism;Metastatic breast cancer;Metastatic Neoplasm to Lymph Nodes;migration;mitochondrial creatine kinase;Molecular;mouse model;mRNA Expression;Names;Neoplasm Metastasis;Nonmetastatic;Normal tissue morphology;novel;Nucleic Acids;Organ;overexpression;Pathology;Pathway interactions;Patients;Phosphocreatine;Primary Neoplasm;prognostic indicator;programs;Proliferating;Property;protein expression;Quantitative Reverse Transcriptase PCR;Reactive Oxygen Species;Research;Research Personnel;Resolution;Role;Sampling;Signal Pathway;Specimen;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Stains;Testing;therapeutic target;Thymidylate Synthase;Tissue Microarray;Tissues;tumor growth;tumor metabolism;tumor progression;Tumor Tissue;Visualization;Western Blotting

PROJECT_TITLE: Reprogramming of creatine metabolism in breast cancer metastasis

STUDY_SECTION: IPCA

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


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Immunotherapy;Infectious Diseases;Vector-Borne Diseases

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Project Narrative: Chronic infection with Trypanosoma cruzi results in chronic inflammation and progressive cardiac fibrosis, known as Chronic Chagasic Cardiomyopathy. Our goal is to better define the mechanisms of inflammation and fibrosis to identify host specific targets for intervention. Ultimately, this approach will identify therapies that can be used in an integrated, multimodal treatment strategy to preserve cardiac health and improve clinical outcomes for patients with CCC.

PI_NAMEs: JONES, KATHRYN MARIE (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: acylcarnitine;Address;Adjuvant;Affect;Agonist;Antigens;Antiparasitic Agents;Benznidazole;Cardiac;Cardiac health;CD8-Positive T-Lymphocytes;Cells;Chagas Disease;chagasic cardiomyopathy;chemotherapy;Chronic;chronic infection;Clinical;Collagen;Combined Modality Therapy;Complementary therapies;Complex;connective tissue growth factor;coronary fibrosis;cytokine;Data;Deposition;Development;Disease;Disease Progression;Dose;Echocardiography;efficacy evaluation;Electrocardiogram;Emulsions;Failure;Fibrosis;Goals;Heart;Heart failure;heart function;heart imaging;heart metabolism;heart preservation;Imaging Techniques;Immune response;Immunotherapy;improved;Infection;Infiltration;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;Intervention;intervention effect;Knowledge;Link;Liver Fibrosis;Measures;Metabolic;Metabolic dysfunction;Metabolic Pathway;mouse model;Mus;Myocardial dysfunction;Myocarditis;Neuropathy;Organ Preservation;Outcome;parasite invasion;Parasites;Pathogenesis;Pathology;Pathway interactions;Patient-Focused Outcomes;Patients;Persons;Phosphorylation;Platelet-Derived Growth Factor;Proteins;Protozoa;Pulmonary Fibrosis;Recombinants;response;Scheme;Severities;Severity of illness;Signal Transduction;skin fibrosis;small molecule;STAT1 gene;STAT3 gene;Sudden Death;synergism;targeted treatment;Therapeutic Intervention;Time;Tissues;TLR4 gene;TNF gene;Transforming Growth Factor beta;treatment strategy;Trypanosoma cruzi;Tyrosine Phosphorylation;Vaccines;Vascular Diseases;vector-borne;Work

PROJECT_TITLE: Mechanisms of myocarditis and progressive cardiac fibrosis in chronic Trypanosoma cruzi infection.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AIDC-Q(83)]


ORG_NAME: MASSACHUSETTS EYE AND EAR INFIRMARY

PHR: NARRATIVE The Harvard-wide Program on Antibiotic Resistance is designed to fill critical gaps in knowledge that will allow new approaches for treating serious infections with antibiotic resistant staphylococci and enterococci to be developed. This is done by identifying and where needed, creating new advanced technologies to gain insight into how these microbes can be targeted by new classes of molecules, and by more thoroughly understanding how they survive treatment with current antibiotics. These critical advances are accomplished through synergistic interaction among a multidisciplinary team ranging in expertise from mathematics to infectious diseases, with each sharing their special insight and working together to achieve goals that otherwise would be unattainable.

PI_NAMEs: GILMORE, MICHAEL S (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Acceleration;Achievement;Antibiotic Resistance;antibiotic resistant infections;Antibiotics;Antimicrobial Resistance;antimicrobial resistant infection;Area;Attention;Bacteria;Biological Sciences;Budgets;Cell membrane;cell type;Cells;cellular imaging;Cessation of life;Collaborations;Communicable Diseases;Communities;community building;Comparative Genomic Analysis;comparative genomics;design;Development;Doctor of Philosophy;Ensure;Enterococcus;ESKAPE pathogens;experimental study;functional genomics;Genomic approach;Genus staphylococcus;Goals;Gram-Negative Bacteria;Growth;Hospitals;Image;Imaging technology;improved;Individual;Industry;Infection;Infection Control;Infrastructure;innovation;insight;Institution;Knowledge;Knowledge Discovery;lecturer;Mathematical Biology;Mathematics;methicillin resistant Staphylococcus aureus;Microbe;Microfluidics;Molecular;Morbidity - disease rate;mortality;Mothers;Multi-Drug Resistance;multidisciplinary;Mutation;new technology;next generation;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Pathogenesis;Pharmaceutical Preparations;Phase;preservation;programs;Public Health;recruit;Research;Research Personnel;Resistance;Resources;response;Risk;Role;Scientist;screening;small molecule;stem;Sum;synergism;Systems Biology;Technology;Therapeutic;Time;transmission process;United States National Institutes of Health;Vancomycin resistant enterococcus;Vancomycin-resistant S. aureus;Work