NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biotechnology;Clinical Research;Genetics;Lung;Rare Diseases

ORG_CITY: HOUSTON

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: Narrative Macrophages are crucial for the recovery from acute inflammation, however, the mechanisms that modulate macrophage function during this process remain unclear. This proposal tests the hypothesis that the induction of miR-147 in macrophages represents an endogenous protective pathway to control lung inflammation through suppression of its target NDUFA4. Our proposal addresses the urgent need to understand the mechanism of macrophage-mediated control of lung inflammation and facilitates the development of new therapeutic targets for acute respiratory distress syndrome.

PI_NAMEs: YUAN, XIAOYI  (contact)

PROGRAM_OFFICER_NAME: ESPINOZA GRANDON, INGRID CECILIA

PROJECT_TERMS: 3' Untranslated Regions;Acute;Acute Respiratory Distress Syndrome;Address;Anti-Inflammatory Agents;Attenuated;Binding;Biological Assay;Biological Process;Clinical Trials;Complex;cytochrome c oxidase;cytokine;Cytokine Gene;Data;design;Development;Disease;experimental study;Genes;Genetic;Genetic Transcription;Goals;Histones;Human;Human Genome;Hypermethylation;Hypoxia Inducible Factor;hypoxia inducible factor 1;improved;in silico;In Vitro;in vivo;Infection;Inflammation;Inflammatory;Injections;innovation;Interleukin-1 beta;Interleukin-6;intravenous injection;Kinetics;Leucocytic infiltrate;loss of function;LoxP-flanked allele;Luciferases;Lung;Lung infections;lung injury;Macrophage;Mediating;Metabolism;Methylation;MicroRNAs;Mitochondria;mouse model;Mus;Myelogenous;Myeloid Cells;nanoparticle;new therapeutic target;novel;overexpression;oxidation;Pathogenesis;Pathway interactions;Phase I Clinical Trials;Phenotype;Post-Transcriptional Regulation;Process;Production;programs;promoter;protective pathway;Proteins;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Pulmonary Inflammation;Recovery;recruit;Regulation;Reporter;Repression;Research;Resolution;response;Role;screening;Small Interfering RNA;Structure of parenchyma of lung;Succinates;Testing;Therapeutic;therapeutic target;tissue injury;TNF gene;transcription factor;Transcriptional Regulation;transcriptome sequencing;Transgenic Mice;Translating;Work

PROJECT_TITLE: Targeting Myeloid Dependent MicroRNAs in Acute Respiratory Distress Syndrome

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


ADMINISTERING_IC: AR

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Biotechnology;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Transplantation

ORG_CITY: SHREVEPORT

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ORTHOPEDICS

ORG_FIPS: US

ORG_NAME: LOUISIANA STATE UNIV HSC SHREVEPORT

ORG_STATE: LA

PHR: We have recently identified the Notch pathway as an important regulator of stem cell maintenance and differentiation. The goal of this study is to use Notch signaling to enhance expansion of bone marrow derived mesenchymal stromal cell (MSC) and subsequent MSC sheet-mediated allograft healing. Data generated by this proposal will likely 1) identify optimized cell populations for generating tissue engineered periosteum (next generation MSC sheets), 2) develop a novel therapeutic approach to enhance the repair of massive devitalized bone allograft and lead to advances in treatments that affects the lives of patients with large bone defects, and 3) pave the path for large pre-clinical animal studies and subsequent clinical trials.

PI_NAMEs: DONG, YUFENG  (contact)

PROGRAM_OFFICER_NAME: MARQUITZ, ARON

PROJECT_TERMS: Address;Affect;allogenic bone transplantation;Allografting;angiogenesis;Animals;Autologous Transplantation;Binding;Biological Assay;biomechanical test;Blood Vessels;bone;Bone callus;bone healing;bone lead;Bone Marrow;Bone Marrow Aspiration;bone marrow mesenchymal stem cell;bone repair;Bone Tissue;Bromodeoxyuridine;Cell Aging;Cell Culture Techniques;Cell Differentiation process;Cell Lineage;Cell Maintenance;Cells;Cellular Metabolic Process;Characteristics;chromatin immunoprecipitation;Clinical Trials;Data;Defect;Endothelial Cells;Enzyme-Linked Immunosorbent Assay;Exhibits;experimental study;Extracellular Matrix;failure Implantation;Femur;Flow Cytometry;Future;gain of function;Generations;Genes;Goals;healing;histological stains;Human;Immunohistochemistry;Impairment;Implant;in vivo;Label;laser capture microdissection;Ligands;long bone;loss of function;Mediating;Mesenchymal Stem Cells;mesenchymal stromal cell;Methodology;microCT;Molecular;Monitor;mouse model;Mus;Mutagenesis;next generation;notch protein;novel;novel therapeutic intervention;Operative Surgical Procedures;Osteogenesis;osteogenic;Oxidative Stress;Pathway interactions;Patients;Periosteum;Population;pre-clinical;Process;promoter;Recombinants;Regulation;repaired;Role;Signal Induction;Signal Transduction;Site;skeletal;Skeletal Development;Stains;stem cell proliferation;stem cells;stemness;Stromal Cells;success;Temperature;Testing;Therapeutic;Tissue Engineering;tissue regeneration;tissue repair;transcription factor;transdifferentiation;Transfection;Transplantation;TWIST1 gene;United States;Up-Regulation;Vascularization;Work

PROJECT_TITLE: Notch-enriched Mesenchymal Stromal Cells for Bone Allograft Repair

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: DALLAS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PUBLIC HEALTH RELEVANCE Sepsis affects millions and kills hundreds of thousands of Americans annually. Currently, no therapy exists to stabilize the deleterious response of the host to invasive infection. In this application, we propose to conduct research on a molecular pathway that appears to be highly promising for enabling clinicians to individualize treatment decisions in the intensive care unit. This project proposes new ways of understanding genetic risk factors in the Tie2 pathway and their influence on the wide spectrum of sepsis manifestations in order to move our community closer to the promise of personalized medicine in the intensive care unit.

PI_NAMEs: PARIKH, SAMIR M (contact)

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: Acute Respiratory Distress Syndrome;adverse outcome;Affect;American;Angiopoietin-2;Angiopoietins;antagonist;Blood Vessels;Caring;Cessation of life;Collaborations;Communities;Critical Illness;Elements;Endothelium;Extravasation;Functional disorder;Gene Expression;Genetic Determinism;genetic epidemiology;Genetic Polymorphism;genetic risk factor;Genome engineering;Hemostatic function;Human;humanized mouse;Immune response;Individual;individualized medicine;Infection;Intensive Care;Intensive Care Units;Ligands;Measures;Metabolic;Metabolism;Microcirculation;Modeling;Molecular;mouse model;National Heart, Lung, and Blood Institute;Organ;Pathway interactions;Patient Care;Peripheral;personalized medicine;Physiological;Positioning Attribute;public health relevance;Qualifying;Research;response;risk prediction;Sepsis;Stress;TEK gene;Thrombosis;TIE-2 Receptor

PROJECT_TITLE: Tie2-driven vascular control in critical illness


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: ATHENS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: PROJECT NARRATIVE Filarial nematodes from the family Onchocercidae, including Brugia malayi, cause the devastating human filarial diseases, elephantiasis and river blindness. These nematodes can only cause disease in humans if they are also infected by a bacterium, Wolbachia pipientis. Understanding mechanisms of Wolbachia survival within these nematodes can provide new information towards the treatment of human filarial diseases and a fundamental understanding of pathogenic nematode biology.

PI_NAMEs: STARAI, VINCENT JOSEPH (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TITLE: Wolbachia disrupts eukaryotic endolysosomal membrane dynamics

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


ADMINISTERING_IC: OD

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: MILWAUKEE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Project Narrative This R24 resource grant builds upon our existing infrastructure to develop the 96 strain Hybrid Rat Diversity Panel (HRDP) to be used to broadly study disease mechanisms, the impact of the environment, and for therapeutic drug development. This panel of rats can be used to map complex traits through powerful analyses of genomic, transcriptomic and phenotypic data. In addition, the HRDP provides a genetically stable population that can be reused and renewed.

PI_NAMEs: DWINELL, MELINDA R (contact)

PROGRAM_OFFICER_NAME: MIROCHNITCHENKO, OLEG

PROJECT_TERMS: addiction;Age;Aging;Alcohols;Animal Model;animal resource;Animals;Anxiety;Arthritis;Asthma;Atlases;biobank;Biological;Breeding;catalyst;clinical translation;clinically relevant;Colorado;Communities;Complex;Controlled Environment;cost;Cost of Illness;Cryopreservation;Czech Republic;Data;Data Analyses;Derivation procedure;Development;Diabetes Mellitus;Discipline;Disease;disease mechanisms study;Disease Progression;Disease susceptibility;disorder risk;DNA Sequence;drug development;Embryo;embryo cryopreservation;Ensure;Environment;Environmental Impact;Environmental Risk Factor;epigenome;Exercise;Exposure to;Female;forward genetics;Foundations;Funding;Future;Gene Targeting;Genetic;Genetic Heterogeneity;Genetic Polymorphism;Genetic Predisposition to Disease;Genetic study;Genetic Transcription;Genetic Variation;Genome;genome browser;genome sequencing;genomic data;genomic locus;Genomics;Goals;Grant;Human;Hybrids;Hypertension;Inbred Strain;Inbred Strains Rats;Inbreeding;Infrastructure;interest;Japan;Kidney;Knowledge;Laboratory Research;Location;male;Malignant Neoplasms;Maps;medical schools;metabolome;Missouri;Modeling;Molecular;Muscle;outreach;Pharmaceutical Preparations;Pharmacogenomics;Phenotype;phenotypic data;Physiological;Population Heterogeneity;Positioning Attribute;potential biomarker;precision medicine;preference;programs;Proteome;public repository;Publications;R24;Rat Genome Database;Rattus;Recombinant Inbred Strain;Recombinants;Recovery;Reproducibility;reproductive system disorder;Research;Research Personnel;Resources;Resuscitation;Sample Size;Sex Differences;Site-Directed Mutagenesis;Source;Stable Populations;stressor;Stroke;symposium;System;Therapeutic;therapeutic target;Thymus Gland;Tissues;tool;trait;transcriptome;transcriptome sequencing;transcriptomics;Translating;Translations;Universities;Update;Variant;Visualization;Visualization software;webinar;whole genome;Wisconsin

PROJECT_TITLE: Hybrid Rat Diversity Program

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GGG-G(55)R]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Women's Health Research

ORG_CITY: ATLANTA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: MOREHOUSE SCHOOL OF MEDICINE

PHR: Project Narrative: Circadian clocks impact nearly every aspect of our health, and their chronic disruption by working on a rotating shift schedule can cause a variety of diseases, including obesity. New findings indicate that the mechanisms involved are highly sex-specific and contribute broadly to the overt biological differences between males and females. The experiments proposed in our application seek to identify these novel circadian clock mechanisms.

PI_NAMEs: DEBRUYNE, JASON P (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TITLE: Role of sex and protein degradation in the circadian clock

STUDY_SECTION: MRAD

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - D Study Section[MRAD]


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

ORG_CITY: FARMINGTON

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: NARRATIVE Proposed project investigates how DNA regions of key genes inherited from the mother and father interact with each other to regulate gene expression in stem cells. This mechanism can help stem cells to continuously produce mature cells in the tissue. Disruption of such process causes multiple human diseases, including cancer and tissue degeneration, and our findings will contribute to understanding these pathologies.

PI_NAMEs: INABA-OGURO, MAYU  (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Alleles;Cell Differentiation process;cell type;Cells;Chromatin;Chromosomes;Development;DNA;Down-Regulation;Drosophila genus;Epigenetic Process;experimental study;Fathers;Funding;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;genome-wide;genomic locus;Germ Lines;germline stem cells;Histone H3;Histone H4;Histones;Homologous Gene;human disease;in vivo;Inherited;male;Malignant Neoplasms;Meiotic Recombination;Modeling;Mothers;Organism;Pathology;pluripotency;Process;programs;Regulation;Role;STAT protein;stem cell differentiation;stem cell division;stem cells;System;tissue degeneration;Tissues

PROJECT_TITLE: Mechanisms of Gene Regulation During Asymmetric Stem Cell Division

STUDY_SECTION: MRAC

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


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative Cell migration is an important process that occurs in many physiological and pathophysiological contexts, including embryogenesis, inflammation, wound healing and tumor metastasis. Our published and preliminary data indicate a previously unrecognized role for contacts between the endoplasmic reticulum and the plasma membrane in the migration of metastatic cells. This project seeks to understand the mechanisms by which calcium influx and lipid transfer are coordinated at these sites, and how they regulate cell motility.

PI_NAMEs: CASANOVA, JAMES E. (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Actins;Adhesions;ADP-Ribosylation Factors;AMPA Receptors;Attention;Automobile Driving;Calcium;Calcium Channel;Calcium Signaling;Cell membrane;cell motility;Cell Physiology;Cells;Complex;Cytoskeleton;Data;Embryonic Development;Endocytosis;Endoplasmic Reticulum;excitatory neuron;Failure;Family;Focal Adhesions;Goals;Guanosine Triphosphate Phosphohydrolases;Human;Inflammation;Integrins;Lecithin;lipid transfer protein;Lipids;member;Membrane;Microtubules;migration;Molecular;Mutation;Neoplasm Metastasis;Neuroglia;novel;Patients;Phosphatidylinositols;Physiological;postsynaptic;Process;protein function;Protein Isoforms;Proteins;Publishing;Reporting;response;rho;Role;Site;trafficking;tumor;Vesicle;wound healing;X-linked intellectual disability

PROJECT_TITLE: ARFs, ORPs and the control of cell migration


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Heart Disease;Patient Safety;Transplantation

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Project Narrative: The clinical and financial burden of aortic stenosis (AS) in the United States (US) is high with ~780,000 patients >60 years of age suffering from severe AS. Transcatheter aortic valve replacement (TAVR) has emerged as a safe and effective therapeutic option for patients with symptomatic severe AS with >50,000 TAVRs now being performed annually across >500 hospitals in the US. This study will enable us to identify practices and processes of care associated with lower rates of death, complications, and readmissions after TAVR at top-performing hospitals, with the hope to share these ‘best practices’ across all hospitals in the US to improve outcomes of patients with severe AS undergoing TAVR.

PI_NAMEs: KOLTE, DHAVAL SANJEEV (contact)

PROGRAM_OFFICER_NAME: LIDMAN, KARIN FREDRIKSSON

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Adopted;Adverse event;Advisory Committees;Age Years;American College of Surgeons;aortic valve replacement;Aortic Valve Stenosis;Award;Biometry;Cardiology;Cardiovascular system;career;career development;Caring;Characteristics;Clinical;comorbidity;comparative;Data;Death Rate;demographics;design;Development Plans;Evaluation;evidence base;Financial Hardship;Funding;Goals;Guidelines;Heart Valve Diseases;Heart Valves;Hemorrhage;Hospital complications;hospital readmission;Hospitals;improved;improved outcome;Intervention;intervention program;Interview;Learning;Length of Stay;Life;Logistic Regressions;Mentored Patient-Oriented Research Career Development Award;Mentors;Methods;Modeling;Morbidity - disease rate;mortality;Outcome;Outcomes Research;Patient Selection;Patient-Focused Outcomes;Patients;Performance;Policies;Procedures;Process;Process Measure;programs;Qualitative Research;readmission rates;Registries;Research;Research Methodology;Research Personnel;Risk;Risk Adjustment;Sampling;Selection Criteria;Self Management;skills;Societies;Standardization;Stroke;Structure;surgical risk;Techniques;theories;therapeutically effective;Thoracic Surgeon;Training;United States;United States Food and Drug Administration;Variant

PROJECT_TITLE: Identifying Modifiable Practices Related to Outcome Variation and Enhancement in Transcatheter Aortic Valve Replacement (IMPROVE TAVR)

STUDY_SECTION: MPOR

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


NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Regenerative Medicine;Wound Healing and Care

ORG_CITY: ANN ARBOR

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Techniques to stimulate the controlled growth of blood vessels could help the translation of engineered tissues and treatment of ischemic tissue. In this project, we will advance the development of an implant that releases angiogenic growth factors in response to ultrasound. Results from the proposed studies will further acellular and cell-based approaches for vascularization as well as broadly assist other ultrasound-based, biomedical therapies.

PI_NAMEs: FABIILLI, MARIO LEONARDO (contact)

PROGRAM_OFFICER_NAME: LUNDBERG, MARTHA

PROJECT_TERMS: Acoustics;Advanced Development;Affect;Biocompatible Materials;blood perfusion;blood vessel development;Blood Vessels;Cardiovascular Diseases;cell motility;Cell Survival;Cell Therapy;Cells;Clinical;Clinical Trials;controlled release;critical limb Ischemia;Development;Disease;Emulsions;Encapsulated;Endothelial Cells;Engineering;Ensure;Exposure to;FGF2 gene;Focused Ultrasound;Funding;Goals;Growth;Growth Factor;Hydrogels;Implant;in vivo;Ischemia;Kinetics;Knowledge;limb ischemia;Mechanics;Mediating;Microscopy;millimeter;Modeling;mouse model;Outcome;Penetration;Perfusion;Pericytes;Peripheral arterial disease;permissiveness;Platelet-Derived Growth Factor;platelet-derived growth factor BB;Pre-Clinical Model;Property;Regenerative Medicine;release factor;response;scaffold;spatiotemporal;Specificity;Speed;Stromal Cells;Structure;subcutaneous;success;technique development;Techniques;Technology;Testing;Therapeutic;therapeutic angiogenesis;Therapeutic Trials;Tissue Engineering;tissue regeneration;Tissue Viability;Tissues;Translations;ultrasound;vaporization;Variant;Vascular regeneration;Vascularization

PROJECT_TITLE: Angiogenic growth factor delivery for vascular regeneration in critical limb ischemia using acoustically-responsive scaffolds

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-J(02)M]


PHR: PROJECT NARRATIVE  Autonomous aldosterone production from one or both adrenal glands (primary aldosteronism, PA) leads to hypertension, low potassium and, if not recognized and appropriately treated, serious cardiac and renal complications. The current methods to diagnose and guide treatment of PA are complicated, invasive (adrenal vein sampling) and reliant on referral centers. The proposed research aims to implement comprehensive histologic, genomic and steroid profiling analyses to develop a simple peripheral blood test which would accurately distinguish between PA forms (uni- vs. bilateral) and other causes of hypertension.

PI_NAMEs: TURCU, ADINA F (contact)

PROGRAM_OFFICER_NAME: OH, YOUNGSUK

PROJECT_TERMS: Address;adenoma;Adrenal Gland Diseases;Adrenal Gland Neoplasms;Adrenal Glands;adrenal hypertension;Affect;Aldosterone;antagonist;ATP1A1 gene;Bilateral;Biological Markers;biomedical referral center;Blood;Blood Tests;Cardiac;cardiovascular risk factor;Cardiovascular system;Caring;Cells;Classification;Clinical;Common Neoplasm;Community Practice;Corticotropin;cost;Costs and Benefits;Cosyntropin;Data;Data Analyses;design;Detection;Dexamethasone;Diagnosis;Diagnostic;Disease;Essential Hypertension;Fingerprint;Functional disorder;General Practitioners;Genes;Genomics;Genotype;Goals;Heterogeneity;High Prevalence;Histologic;Hormonal;Hybrids;Hyperaldosteronism;Hypertension;hypertension treatment;Image;Immunohistochemistry;Ion Channel;Ion Pumps;Kidney;Lesion;Mass Spectrum Analysis;Measures;Medical;medical specialties;Methods;Mineralocorticoid Receptor;Morbidity - disease rate;mortality;Mutate;Mutation;next generation sequencing;novel;Operative Surgical Procedures;Patients;Peripheral;peripheral blood;personalized care;pharmacologic;Phenotype;Potassium;Potassium Channel;prevent;Procedures;Production;Protocols documentation;Provider;Public Health;Quality of life;Research;Resistant Hypertension;response;Sampling;Serum;Somatic Mutation;Source;standard of care;Standardization;Steroids;Techniques;Temperature;Testing;Tissues;tool;tumor;Variant;Veins;voltage

PROJECT_TITLE: Primary Aldosteronism Subtypes: Pathophysiology and Steroid Signatures

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

ORG_CITY: DAVIS

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: 1 Project Narrative (three sentences). Sulfated molecules, their interacting partners and 2 associated signaling complexes play critical roles in the health of humans and other 3 species. Our research will reveal fundamental mechanisms governing these processes. 4 Knowledge gained from the study will guide strategies to develop peptide-based 5 reagents capable of inhibiting or activating molecular interactions with a high degree of 6 affinity and specificity with potential applications in research, agriculture and medicine.

PI_NAMEs: RONALD, PAMELA C (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Address;Affinity;Agriculture;Animals;Antigen-Antibody Complex;Area;Awareness;Bacteria;Binding;Biological Assay;Biological Process;blood treatment;Cardiovascular Diseases;Cell surface;Cells;Coagulation Process;Complex;Development;Engineering;Foundations;gene discovery;Goals;Health;HIV;Human;Immune;Immune response;insight;Knowledge;Ligand Binding;Medicine;microorganism interaction;Modification;mutant;novel;Peptides;Phenotype;Plants;Play;Positioning Attribute;Process;protein protein interaction;Proteins;Reagent;receptor;Research;response;Role;Signal Transduction;Specificity;Spectrometry;Sulfate;therapeutic evaluation;Ticks;tool;tyrosine O-sulfate;United States National Institutes of Health;whole genome;Yeasts

PROJECT_TITLE: Sulfotyrosine, an essential determinant for diverse protein-protein interactions

STUDY_SECTION: MRAB

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


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Skin Cancer;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Project Narrative Highly prevalent skin cancers such as squamous and basal cell carcinomas arise from hair follicles as well as from epidermal stem cells; therefore, delineating the controls of hair follicle stem cell function has relevance for understanding skin carcinogenesis as well as hair loss diseases. This project aims to determine how diverse signaling inputs are coordinated to impact transcription factor activity at the level of hair follicle stem cell chromatin, and has potential to identify novel therapeutic intervention points and targets.

PI_NAMEs: MILLAR, SARAH E. (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: Address;Affect;ATAC-seq;Basal cell carcinoma;beta catenin;Binding;Binding Sites;Biochemical;Biological Assay;Cell Fate Control;cell type;Cells;ChIP-seq;Chromatin;Chromatin Remodeling Factor;Collaborations;Communication;Complex;Data;Data Set;derepression;Disease;Enhancers;epidermal stem cell;Epidermis;Epigenetic Process;Epithelial Cells;experimental study;Failure;Family member;fibroblast growth factor 18;FOXC1 gene;FOXP1 gene;Functional disorder;Gene Expression;gene interaction;Genes;Genetic;Genetic Transcription;Genomic approach;Growth;Hair;Hair follicle structure;Hair shaft structure;HDAC1 gene;HDAC3 gene;Histone Acetylation;Histone Deacetylase;induced pluripotent stem cell;intestinal epithelium;Intestines;LGR5 gene;Ligation;Malignant Epithelial Cell;Mediating;mouse model;mutant;novel;novel therapeutic intervention;novel therapeutics;Nuclear;Nucleosomes;Output;Overlapping Genes;Peptide Initiation Factors;premature;Process;Proliferating;promoter;recruit;regenerative;Regulator Genes;Reporter;Repression;response;Signal Transduction;Skin;Skin Cancer;Skin Carcinogenesis;skin disorder;Squamous cell carcinoma;stem cell function;stem cells;TCF3 gene;TCF7L2 gene;Testing;transcription factor;transcriptome sequencing;WNT Signaling Pathway

PROJECT_TITLE: KLF-mediated coordination of signaling and epigenetic mechanisms in the skin


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: EAST LANSING

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: MICHIGAN STATE UNIVERSITY

PHR: PROJECT NARRATIVE This proposal will establish an integrated platform for diploid germplasm conservation in zebrafish (Danio rerio), one of the most rapidly growing animal models of human disease. The successful completion of the work will increase vigor and reproducibility in experiments, reduce cost, and help distribute new zebrafish models among the scientific community.

PI_NAMEs: CIBELLI, JOSE B (contact)

PROGRAM_OFFICER_NAME: CONTRERAS, MIGUEL A

PROJECT_TERMS: Address;agricultural center;Alleles;animal cloning;Animal Model;autism spectrum disorder;Biological Assay;Cell Separation;Cell Therapy;Cell Transplantation;cell type;Cells;Cloning;Collaborations;Communities;cost;Cryopreservation;Derivation procedure;Development;developmental genetics;Diploid Cells;Diploidy;Disease;DNA Modification Process;DNA Sequence;egg;Embryo;embryo cryopreservation;established cell line;experimental study;Extinction;Female;Fishes;Funding;gene function;gene therapy;Generations;Genes;Genetic Drift;genetic resource;Genome;genome editing;genomic locus;Genotype;Germ;Goals;Haploidy;human disease;human model;Human Resources;Hybrids;Individual;International;Laboratories;laboratory experience;Laboratory Personnel;Louisiana;male;Malignant Neoplasms;mature animal;Methods;Michigan;Modeling;mutant;National Human Genome Research Institute;Oregon;Organ Transplantation;Output;pathogen;Preparation;preservation;Procedures;Process;Protocols documentation;Publishing;quality assurance;Quality Control;R24;Replacement Therapy;Reproducibility;Research;Resources;Sampling;Scientist;sex;sex determination;Shipping;Somatic Cell;somatic cell nuclear transfer;sperm cryopreservation;Standardization;Techniques;Time;Toxicology;Training;United States National Institutes of Health;Universities;whole genome;Work;Zebrafish;zebrafish genome

PROJECT_TITLE: Establishing an Integrated Platform for Diploid Germplasm Conservation in Zebrafish (Danio rerio)


NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Lung;Neurodegenerative;Neurosciences;Precision Medicine;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Narrative Respiratory failure is the most common cause of death in amyotrophic lateral sclerosis (ALS), which is a variably progressive neurologic disease without a known cure. Using a previously developed prediction model for respiratory failure, the current research will identify patients at high risk of respiratory failure upon diagnosis, will gather patient input on respiratory care early in disease, and will perform a small trial of a pulmonary exercise in patients at high risk of respiratory failure. This work will set the stage for larger trials of early respiratory therapies on high-risk patients, so that we may develop a personalized approach to treating respiratory failure in ALS.

PI_NAMEs: ACKRIVO, JASON  (contact)

PROGRAM_OFFICER_NAME: KALANTARI, ROYA

PROJECT_TERMS: Address;ALS patients;Alveolus;Amyotrophic Lateral Sclerosis;amyotrophic lateral sclerosis therapy;Applications Grants;arm;Articular Range of Motion;aspirate;Belief;Caregivers;Caring;Cause of Death;Cessation of life;Characteristics;Chest wall structure;Chronic;Clinical;clinical effect;clinical practice;clinical predictors;Clinical Trials;cohort;Cohort Studies;cost;Coughing;Data;design;Development;Diagnosis;Disease;effective intervention;Elasticity;Emotional;Enrollment;Event;Evolution;Exercise;Expert Opinion;Future;Goals;Guidelines;High Prevalence;high risk;Hypercapnic respiratory failure;Hypoventilation;improved;improved outcome;innovation;insight;Intervention;Intervention Studies;Interview;Investigation;Knowledge;longitudinal, prospective study;Lung;Lung infections;lung volume;Maintenance;Methodology;Modeling;Monitor;Morbidity - disease rate;mortality;Multicenter Studies;Muscle Weakness;Nervous System Disorder;Neurodegenerative Disorders;Neurologic;neuromuscular;Newly Diagnosed;novel;novel strategies;Observational Study;Outcome;Outcome Study;Outpatients;patient oriented;patient population;Patient Selection;patient subsets;Patients;personalized approach;personalized medicine;Phenotype;Philadelphia;Physical therapy;Physicians;Pilot Projects;pilot trial;Population;predictive modeling;predictive tools;Prevalence;prospective;Prospective Studies;Prospective, cohort study;Protocols documentation;Publishing;Qualitative Methods;randomized, clinical trials;Randomized, Controlled Trials;recruit;Research;Research Project Grants;respiratory;Respiratory Failure;respiratory morbidity;Respiratory physiology;Respiratory Therapy;Resuscitation;Retrospective Studies;Risk;risk stratification;Sampling;Structure;Subgroup;Symptoms;Time;Training;trial design;Uncertainty;ventilation;virtual;Vital capacity;Work

PROJECT_TITLE: Early Respiratory Care in Amyotrophic Lateral Sclerosis Patients at High Risk for Respiratory Failure


ORG_CITY: CHAPEL HILL

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE HIV-1 antiviral therapy must be taken continuously to prevent viral rebound due to the presence of a latent viral reservoir. We have found that the initiation of antiviral therapy changes the environment within the host to promote the formation of a large majority of the latent reservoir at this time. The proposed studies will extend these observations to examine other forms of the latent reservoir and to explore the stability of the reservoir after the return of an inflammatory state. We will also examine the differentiation state of the cells that are carrying the latent virus before and after therapy. Collectively these studies will provide a framework for developing new strategies to inhibit the formation of that part of the viral reservoir that forms during therapy initiation.

PI_NAMEs: SWANSTROM, RONALD I (contact)

PROGRAM_OFFICER_NAME: LAWRENCE, DIANE M

PROJECT_TERMS: Address;Anti-viral Therapy;Antigens;antiretroviral therapy;Apoptosis;Archives;Award;Behavior;Biological;Blood;Blood Cells;CD4 Positive T Lymphocytes;cell type;Cells;Clinical;clinical research site;Collaborations;Collecting Cell;cytokine;Data;Data Analyses;Emodin;Environment;Event;experience;Funding;Future;Genome;HIV;HIV-1;Holidays;Individual;Infection;Inflammation;Inflammatory;insight;International;Interphase Cell;latent HIV reservoir;Lymph Node Tissue;Lymphoid Tissue;men;Nature;North Carolina;Pattern;Pharmaceutical Preparations;Population Heterogeneity;prevent;Recording of previous events;Research;Rest;Sampling;South Africa;superinfection;Sweden;T-Lymphocyte;T-Lymphocyte Subsets;Time;Tissues;United States National Institutes of Health;Universities;Veins;Viral;viral DNA;viral rebound;Viral reservoir;Virus;Virus Latency;Virus Replication;Woman;Women's cohort;Work

PROJECT_TITLE: Formation of the HIV-1 Latent Reservoir

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]


NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Obesity;Racial and Ethnic Minority Health Research

ORG_CITY: CORAL GABLES

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Project Narrative Atrial fibrillation is the most common heart rhythm disorder, with a 25% lifetime risk of developing atrial fibrillation once an individual reaches the age of 40 years. Obesity, a very prevalent condition, and epicardial adipose tissue are associated with atrial fibrillation and may be involved in the pathogenesis of the atrial substrate leading to atrial fibrillation; importantly, weight loss improves treatment for atrial fibrillation. This study will assess the proteomic, transcriptomic, and metabolomic features linking epicardial adipose tissue to atrial fibrillation, in order to identify new targets for prevention and treatment.

PI_NAMEs: GOLDBERGER, JEFFREY J (contact)

PROGRAM_OFFICER_NAME: YAN, YE

PROJECT_TERMS: activin A;Address;adipokines;Adipose tissue;Adrenergic Receptor;Affect;Age;American;Anti-Arrhythmia Agents;Arrhythmia;Atherosclerosis;Atrial Fibrillation;attenuation;Biological Markers;Biopsy;Black race;Blood;Blood specimen;Body Weight decreased;Branched-Chain Amino Acids;Calcium Signaling;Cardiac;Cardiac ablation;Cardiac Surgery procedures;Cardiology;Catecholamines;Cell Adhesion;Clinical;Clinical Data;Collagen;college;Communication;comparison control;Coronary;Data;Defect;Development;Diagnostic;diagnostic platform;diagnostic strategy;Disease;effective therapy;Enrollment;Enzymes;ethnic difference;Ethnic Origin;Ethnic Population;Evaluation;Fascia;Fatty acid glycerol esters;Fibrosis;Gene Expression Regulation;Genes;Goals;Health Expenditures;Heart;Heart Atrium;heart rhythm;Hispanic;Image;improved;Incidence;Individual;Inflammation;Inflammatory;insight;interest;Interleukin-6;Journals;Knowledge;Left;Left Atrial Function;lifetime risk;Link;Lipoproteins;Longitudinal Studies;Matrix Metalloproteinases;Measures;Mediator;Metabolism;Metabolite Interaction;metabolome;metabolomics;Multi-Ethnic Study of Atherosclerosis;multi-racial;multiple omics;Muscarinic Acetylcholine Receptor;Myopathy;Natriuretic Peptides;novel;novel diagnostics;novel strategies;novel therapeutic intervention;Obesity;Outpatients;Oxidative Phosphorylation;Oxidative Stress;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Pericardial body location;Peripheral;personalized medicine;Persons;Plasma;Play;Prevention;Process;Proteins;Proteome;Proteomics;Publishing;Race;racial difference;racial population;receptor function;Recurrence;Risk;RNA Splicing;Role;Signal Pathway;Sinus;State-of-the-Art Reviews;subcutaneous;Techniques;Testing;therapeutic target;Thrombosis;Tissues;Transcript;transcriptome;transcriptome sequencing;transcriptomics;United States;Untranslated RNA;Up-Regulation;Validation;validation studies;Variant;Vascular blood supply;X-Ray Computed Tomography

PROJECT_TITLE: Trans-omic analysis of epicardial adipose tissue in atrial fibrillation

STUDY_SECTION: CICS

STUDY_SECTION_NAME: Clinical and Integrative Cardiovascular Sciences Study Section[CICS]


NIH_SPENDING_CATS: Hematology;Rare Diseases;Sickle Cell Disease

PHR: PROJECT NARRATIVE The goal of this project is to evaluate whether activation of beneficial PAR1 signaling can attenuate the chronic pro-coagulant state of sickle cell disease, with a goal of reducing vaso-occlusive crisis, acute chest syndrome, and end-organ damage.

PI_NAMEs: SPARKENBAUGH, ERICA M (contact)

PROGRAM_OFFICER_NAME: ZOU, SHIMIAN

PROJECT_TERMS: activated Protein C;acute chest syndrome;Affect;aging population;Agonist;Anti-Inflammatory Agents;Anticoagulants;Antiinflammatory Effect;Attenuated;beta Globin;Blood Platelets;Blood Vessels;Cardiovascular system;Cell Physiology;Cells;Cessation of life;Chronic;Coagulation Process;combat;Complex;Cytoprotection;Data;Disease;Disease Management;Endothelial Cells;Endothelium;Erythrocytes;Etiology;extracellular;Functional disorder;G-Protein-Coupled Receptors;Generations;Genes;Genetic;genetic manipulation;Goals;Hemolytic Anemia;Hospitalization;Human;improved;Infection;Inflammation;Inflammatory Response;insight;Lead;life span;Long-Term Effects;Mediating;Mediator;Methods;mortality;mouse model;multimodality;Mus;mutant;Mutation;Newborn Infant;Nucleotides;Organ;Oxidative Stress;Pain;PAR-1 Receptor;Pathology;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Point Mutation;premature;Protease Inhibitor;Publishing;receptor;Reperfusion Injury;Role;Sickle Cell;Sickle Cell Anemia;sickling;Signal Induction;Signal Pathway;Signal Transduction;Testing;Therapeutic;Thrombin;Thrombin Receptor;thromboinflammation;Time;Transgenic Mice;vascular inflammation;vaso-occlusive crisis;Work

PROJECT_TITLE: Biased PAR1 Agonism in Sickle Cell Disease

STUDY_SECTION: HT

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Epilepsy;Neurodegenerative;Neurosciences

ORG_CITY: Los Angeles

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE Memory deficits are a common complication from the surgical resection or ablation of the hippocampus in the treatment of mesial temporal lobe epilepsy (MTLE). Modern surgical techniques allow very precise targeting of the hippocampus, but clinicians need better tools to preview the postoperative memory deficits at this same precision. We will examine whether electrical stimulation through stereoelectroencephalography (SEEG) electrodes placed in the hippocampus, a procedure already required for some patients with MTLE, can generate memory deficits and thus be of clinical use to preview the effect of resecting more precise volumes of tissue.

PI_NAMEs: KELLIS, SPENCER ;LEE, BRIAN  (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TITLE: Inactivation of the hippocampus by electrical stimulation to preview post-surgical verbal recognition memory deficits

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: IOWA CITY

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Many children with autism spectrum disorder (ASD) have enlarged dorsal striatum and striatal-dependent learning problems, which may be central to clinically significant impairments. Prenatal stress is a risk factor for ASD; translatable targets for prevention and intervention of ASD are goals of studying prenatal stress in model systems. We will study a novel mechanism—increased striatal neuron generation—in mouse models of prenatal stress, test its importance for striatal growth and striatal-dependent learning, and examine its regulation by prenatal maternal and placental mechanisms which we and others have implicated in prenatal stress.

PI_NAMEs: STEVENS, HANNA E (contact)

PROGRAM_OFFICER_NAME: TONELLI, LEONARDO HERALDO

PROJECT_TERMS: Address;Adolescent;Adult;Affect;Age;Agonist;Animals;Antibodies;autism spectrum disorder;autistic children;Behavioral;Biological Models;Brain;Cell Cycle;Cell Physiology;Cell Proliferation;Child;Chronic;Circulation;clinically significant;Corpus striatum structure;cytokine;Data;Development;disorder risk;Dorsal;Electrophysiology (science);Embryo;Embryonic Development;embryonic stem cell;Etiology;experimental study;Exposure to;Family;fetal;Generations;Goals;Growth;Growth Factor;Habits;Immunohistochemistry;Impairment;in utero;in vivo;Inflammatory;Injections;innovation;Insulin-Like Growth Factor I;Insulin-Like-Growth Factor I Receptor;Interleukin-6;Intervention;juvenile animal;Knock-out;Knowledge;Lateral;learned behavior;Learning;Link;Maternal Physiology;maternal serum;maternal stress;mature animal;Measures;Mediating;Metabotropic Glutamate Receptors;Methods;Modeling;Molecular;Morphogenesis;mouse model;Mus;nerve stem cell;Neurodevelopmental Deficit;Neurodevelopmental Problem;Neurons;novel;novel strategies;offspring;Outcome;Outcome Measure;Physiology;Placenta;Placental Biology;Play;Population;postnatal;prenatal;prenatal stress;prevent;Prevention;Process;progenitor;Ramp;Regulation;restraint;restraint stress;Risk;Risk Factors;Rodent;Role;Series;Signal Transduction;single-cell RNA sequencing;Specificity;stem cells;Stress;Testing;time interval;Tissues;Training;Work

PROJECT_TITLE: Prenatal striatal morphogenesis: maternal and placental contributions and behavioral consequences


NIH_SPENDING_CATS: Biotechnology;Chronic Obstructive Pulmonary Disease;Cystic Fibrosis;Genetics;Infectious Diseases;Lung;Orphan Drug;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Tobacco;Tobacco Smoke and Health

ORG_CITY: HOUSTON

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF HOUSTON

PHR: Project Narrative Inflammation in the lungs of cystic fibrotic patients continues despite treatment with the new class of CFTR modulator drugs. Like COPD, we find that CF lungs are inundated with hyperinflammatory lung stem cell variants that likely contribute to this persistent inflammation and may represent therapeutic targets to improve the health of CF patients.

PI_NAMEs: MCKEON, FRANK D. (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: airway epithelium;Antibiotics;Bacteria;Bacterial Infections;Cells;Chronic;Chronic Obstructive Pulmonary Disease;Clinical;Cloning;Complement;Complex;Coupled;CRISPR/Cas technology;Cystic Fibrosis;cystic fibrosis infection;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;Dependence;Development;Disease;Disease Progression;disease-causing mutation;Drug Modulation;Elements;Epithelial Cells;Excision;Ferrets;Fetal Lung;Fibrosis;gene complementation;Gene Expression Profile;Genes;genetic signature;genome editing;Genotype;Health;Human;improved;in utero;Individual;Inflammation;Inflammatory;inflammatory lung disease;insight;Kinetics;Link;Lung;Lung Diseases;Methods;microbial colonization;Modeling;Monitor;mucin hypersecretion;mutant;Mutation;neutrophil;Neutrophil Infiltration;Nodal;novel;novel therapeutics;Organ;pathogenic bacteria;Pathogenicity;Pathology;Patients;Pattern;Pharmaceutical Preparations;Phenotype;Play;Process;Proliferating;Property;prospective;Pulmonary Cystic Fibrosis;pulmonary function;Pulmonary Inflammation;respiratory smooth muscle;response;restoration;Role;smoking abstinence;smoking cessation;stem cells;Testing;Therapeutic;therapeutic target;Time;Variant;VX-770;Withdrawal;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Pro-Inflammatory Stem Cell Variants in Cystic Fibrosis


NIH_SPENDING_CATS: Immunization;Immunotherapy

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: PROJECT NARRATIVE Members of the tumor necrosis factor receptor superfamily (TNFRSF) regulate proliferation of immune cells or induce programmed cell death, and many of them are candidates for antibody-based immunotherapy, e.g., antagonists of TNFR1/2 and CD40 for treating autoimmune and agonists of OX40 and 4-1BB in cancer immunotherapy. Recently, we made an unexpected finding that, for a few members of the TNFRSF, there is a defined auto-inhibitory state that keeps the receptor inactive in the absence of ligand. The proposed research aims to investigate the general applicability of this finding and its mechanistic basis, while developing new antibodies that specifically modulate the auto-inhibitory state for potential treatment of autoimmune diseases and/or cancer.

PI_NAMEs: WAGNER, GERHARD  (contact);WU, HAO

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: Address;Agonist;antagonist;Antibodies;Antibody Affinity;Apoptosis;Autoimmune;Autoimmune Diseases;Automobile Driving;Back;Binding;Biochemistry;cancer immunotherapy;Cells;Cessation of life;Cryoelectron Microscopy;Cytoplasmic Tail;Death Domain;dimer;Environment;Excision;Family;Family member;Goals;high throughput technology;Immune;Immunotherapy;inhibitor;Ligands;Lipid Bilayers;Malignant Neoplasms;Mediating;member;Membrane;Molecular Conformation;Mutagenesis;nanobodies;Negative Staining;OX40;prevent;Proliferating;Property;Protocols documentation;receptor;Receptor Activation;receptor function;Receptor Inhibition;Receptors, Tumor Necrosis Factor, Type II;Research;Role;screening;Signal Transduction;Structure;Surface;Surveys;Technology;Testing;Therapeutic antibodies;therapeutic development;TNFRSF10B gene;TNFRSF1A gene;TNFRSF1B gene;TNFRSF5 gene;TNFRSF8 gene;Tumor Necrosis Factor Activation;Tumor Necrosis Factor Receptor;Yeasts

PROJECT_TITLE: CONTROL AND ACTIVATION OF THE TUMOR NECROSIS FACTOR RECEPTORS

STUDY_SECTION: CMIA

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Kidney Disease

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: The proposed studies will investigate the role of the epidermal growth factor receptor (EGFR) and its ligands in mediation of renal macrophage activity in both acute and chronic kidney injury. The studies will investigate mechanisms of macrophage EGFR activation and polarization of macrophages following renal injury, and the role of release of the EGFR ligand, amphiregulin in mediating tubulointerstitial fibrosis.

PI_NAMEs: HARRIS, RAYMOND C. (contact);ZHANG, MINGZHI

PROGRAM_OFFICER_NAME: SADUSKY, ANNA BURKART

PROJECT_TERMS: Acute;Acute Renal Failure with Renal Papillary Necrosis;Affect;Amphiregulin;betacellulin;Binding;C-terminal;cell type;Cells;Chronic;Chronic rejection of renal transplant;cytokine;Cytoplasmic Protein;Dendritic Cells;Development;Diabetic Nephropathy;DTR gene;EGF gene;Epidermal Growth Factor Receptor;Epiregulin;ErbB Receptor Family Protein;Experimental Models;extracellular;Family;Family member;Fibroblasts;Fibrosis;Genetic;Homologous Gene;Inflammation;Inflammation Mediators;Inflammatory;Injury;Injury to Kidney;Ischemia;ischemic injury;Kidney;Kidney Diseases;kidney fibrosis;Ligand Binding Domain;Ligands;Macrophage;Macrophage Activation;Mediating;Mediation;Mediator;member;Membrane;Myelogenous;Myeloid Cells;Myofibroblast;Organ;Peptide Hydrolases;pharmacologic;Phenotype;Phosphorylation Site;Play;prevent;receptor;Receptor Activation;receptor expression;Receptor Signaling;Recovery;renal damage;renal ischemia;Reperfusion Therapy;Reporting;rhomboid;Role;Signal Pathway;Source;Tail;Therapeutic Intervention;therapeutically effective;TNF gene;Transactivation;Transforming Growth Factor alpha;Tyrosine Kinase Domain

PROJECT_TITLE: Mechanisms of EGFR Activation and Signaling in Kidney Disease

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


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

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: PROJECT NARRATIVE The goals of this application are to investigate the enzymes involved in the production of unusual dideoxysugars found on the lipopolysaccharides of pathogenic Gram-negative bacteria, to study the enzymes required for the biosynthesis of the O-methyl phosphoramidate modification observed in bacterial capsular polysaccharides, and to examine the enzymes needed for the construction of the nonulosonic acids observed in bacterial surface polysaccharides. The components of this application are linked together in that both unusual sugars and modifications thereof play key roles in bacterial invasion and serum resistance.

PI_NAMEs: HOLDEN, HAZEL M. (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TITLE: Biochemical Investigations of Sugar-Modifying Enzymes

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


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Physical Rehabilitation;Rehabilitation

ORG_CITY: SEATTLE

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE This series of studies will contribute to a better understanding of how the brain learns the articulatory movements involved in speech production and how it remains able to adjust those movements based on hearing our own speech sounds. The knowledge gained from this work will make it possible to improve theoretical models of the processes involved in speech sensorimotor learning and to pursue new directions of research on the etiology of developmental speech disorders in which sensorimotor learning may be impaired. In addition, the research findings will suggest innovative techniques for treating speech disorders in children and adults.

PI_NAMEs: MAX, LUDO  (contact)

PROGRAM_OFFICER_NAME: KOPF, LISA MARIE

PROJECT_TERMS: Acceleration;Acoustics;Adult;Affect;Articulation;Auditory;auditory feedback;Basal Ganglia;base;Behavior;Behavioral;Brain;Cell Nucleus;Central Nervous System;Characteristics;Child;Client;Clinical;Clinical Protocols;Compensation;Complex;Computer Assisted;Computer Models;Databases;Deep Brain Stimulation;Development;Developmental apraxia;Electrodes;Etiology;experimental study;Feedback;Frequencies;Future;Generations;Goals;Hearing;Impairment;Implant;improved;Individual;innovation;insight;Instruction;Jordan;Knowledge;Laboratories;Learning;life span;Limb structure;Maintenance;Modeling;Motor;motor behavior;motor control;motor learning;Movement;Nature;neural;neural circuit;Neurologic;neurophysiology;neuroregulation;novel;novel strategies;Output;Participant;Pathway interactions;Patients;Play;Policies;prevent;Procedures;Process;Production;programs;Public Health;Research;Role;sensor technology;Sensory;sequence learning;Series;Signal Transduction;skills;Speech;speech accuracy;Speech Development;Speech Disorders;Speech Sound;Structure of subthalamic nucleus;Stuttering;Techniques;Thalamic structure;Theoretical model;therapy development;Time;Translational Research;Update;Work

PROJECT_TITLE: Behavioral and neural characteristics of adaptive speech motor control

STUDY_SECTION: MFSR

STUDY_SECTION_NAME: Motor Function, Speech and Rehabilitation Study Section[MFSR]


PHR: Narrative The goal of this project is to provide cutting-edge training opportunities and to advance mechanisms of voltage- gated sodium, potassium and calcium channels through our use chemical biological approaches.

PI_NAMEs: AHERN, CHRISTOPHER A (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Adopted;Amplifiers;Arrhythmia;Binding;Binding Sites;Biological;Biology;Calcium Channel;Cardiac;Cations;Cell membrane;Cells;chemical binding;Chemicals;Chemistry;Clinical;Dissection;Environment;Epilepsy;Event;experimental study;extracellular;fighting;Foundations;Goals;Heart failure;Heart Rate;Human;Hypertension;Individual;innovation;Ion Channel;Ion Channel Gating;Ions;Light;Link;Long QT Syndrome;Mammalian Cell;Medicine;Membrane;Methods;Modification;Molecular;Muscle;Muscle Contraction;Neurons;Pain management;Pathway interactions;Peptides;Perception;Pharmaceutical Preparations;Phenylalanine;Phosphorylation;Physiological;Potassium Channel;potassium ion;Process;programs;Protein Conformation;protein structure;Proteins;Research;Resolution;response;Second Messenger Systems;sensor;Shapes;Signal Transduction;Site;skeletal;Sodium Channel;Speed;Therapeutic;training opportunity;Tyrosine;Vertebral column;voltage;voltage gated channel;Voltage-Gated Potassium Channel

PROJECT_TITLE: Chemical biology of voltage-gated cation channels


NIH_SPENDING_CATS: Genetics;Neurosciences;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Project Narrative/Public Health Relevance Statement Our research will impact the knowledge of muscle biology and provide new approaches for human disease treatment. Specifically, we will identify mechanisms responsible for nuclear movement and position to better understand how improper positioning of muscle nuclei occurs and how it impacts normal cell function. The results of this research will highlight genes and cellular mechanisms that may fail to function properly in human muscle diseases.

PI_NAMEs: BAYLIES, MARY K (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: 3-Dimensional;Adaptor Signaling Protein;Address;Architecture;Area;Biochemical;Biological;Biological Assay;Biological Markers;Biology;Cell Nucleus;Cell Physiology;cell type;Cells;Centronuclear myopathy;Coculture Techniques;Communication;CRISPR/Cas technology;Cytoskeleton;Data;Development;Disease;Dissection;Drosophila genus;Drug usage;Dynein ATPase;Electrophysiology (science);Etiology;Experimental Genetics;fly;Funding;Genes;Genetic;genetic approach;genetic manipulation;genetic resource;Goals;Growth;Health;Homeostasis;Homologous Gene;Human;Human Cell Line;human disease;imaging approach;in vivo;insight;insulin signaling;Integrins;Kinesin;Knowledge;Learning;Link;Literature;MAPK8 gene;Metabolic;Metabolism;Methodology;Microtubule-Associated Proteins;Microtubules;Mitochondria;Modeling;Motor;Motor Neurons;Movement;Muscle;Muscle Cells;Muscle Development;Muscle Fibers;Muscle function;muscle physiology;mutant;Myopathy;Myotonic Dystrophy;neuromuscular;neuromuscular activity;Neuromuscular Junction;ninein;Normal Cell;novel strategies;Nuclear;Organelles;Phenotype;Physiological;Positioning Attribute;Process;Proteins;proteostasis;public health relevance;Publishing;regenerative;Research;Role;Sarcomeres;Shapes;Signal Pathway;Signal Transduction;Signaling Protein;Striated Muscles;System;Tendon structure;Testing;therapeutic target;three dimensional cell culture;Time;transcriptome sequencing;Translating;Work

PROJECT_TITLE: Mechanisms and Function of Myonuclear Positioning

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]


NIH_SPENDING_CATS: Mental Health;Neurosciences

ORG_CITY: STANFORD

ORG_DEPT: BIOPHYSICS

ORG_NAME: STANFORD UNIVERSITY

PHR: We plan to decipher the molecular mechanisms of Ca2+-triggered synaptic vesicle fusion and quality control of the presynaptic protein complexes involved. Protein complexes will be studied in increasingly complex systems, starting with studies of purified synaptic vesicles and ultimately, studies of synapses in neuronal cultures. The primary tools will be single-particle cryo-electron microscopy, cryo-electron tomography, and single-molecule/particle-fluorescence microscopy.

PI_NAMEs: BRUNGER, AXEL T (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: 3-Dimensional;Action Potentials;alpha-SNAP;Architecture;ATP Hydrolysis;Binding;Biological Assay;Brain;Calcium Channel;Cell membrane;Cells;cofactor;Complex;Coupled;Cryo-electron tomography;Cryoelectron Microscopy;Cytoplasm;Disulfide Linkage;Engineering;Environment;extracellular;Fluorescence Microscopy;Funding;Hybrids;Image;In Situ;In Vitro;in vivo;Individual;insight;Length;Maps;Mediating;Membrane;Membrane Fusion;Membrane Proteins;millisecond;Molecular;Molecular Conformation;Monitor;Mus;Neurons;neurotransmitter release;Neurotransmitters;P-Q type voltage-dependent calcium channel;particle;Postsynaptic Membrane;postsynaptic neurons;presynaptic;presynaptic neurons;prevent;Probability;Process;protein complex;Proteins;Quality Control;receptor;reconstruction;Recycling;Reporting;Resolution;Role;sensor;single molecule;single-molecule FRET;Site;SNAP receptor;Structure;Synapses;Synaptic Cleft;Synaptic Membranes;Synaptic plasticity;Synaptic Transmission;Synaptic Vesicles;Synaptosomes;synaptotagmin;synergism;syntaxin;syntaxin 1A;System;Testing;tool;VAMP-2;Vesicle;voltage

PROJECT_TITLE: Molecular mechanisms of synaptic neurotransmitter release

STUDY_SECTION: BPNS

STUDY_SECTION_NAME: Biophysics of Neural Systems Study Section[BPNS]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Cooley's Anemia;Gene Therapy;Genetics;Hematology;Orphan Drug;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: SAN FRANCISCO

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Alpha thalassemia (AT) is a disease that affects hemoglobin production; while patients with severe forms of AT require chronic transfusions or a stem cell transplant, there are currently no gene therapy strategies for them, indicating a major unmet medical need. In this proposal, we will design and test three complementary gene therapy or editing strategies that will either result in restoration of alpha globin production, or persistence of embryonic zeta globin production. At the end of these experiments, we expect to have generated substantial pre-clinical data that may be developed into an IND with the FDA for an innovative first-in-human phase I/II clinical trial for ex vivo correction of HSCs from patients with AT.

PI_NAMEs: MACKENZIE, TIPPI  (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Address;Adult;Affect;Alleles;alpha Globin;alpha thalassemia major;alpha-Thalassemia;beta Globin;beta Thalassemia;Binding;Biological Assay;Birth;Blood Transfusion;Caring;Cell Differentiation process;Cell Transplantation;Cells;Chronic;Chronic Disease;Clinic;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Compensation;CRISPR screen;Data;derepression;design;Disease;Dissociation;Embryo;Engraftment;Ensure;Erythrocytes;Erythroid;Erythropoiesis;experimental study;fetal;First Pregnancy Trimester;first-in-human;Frequencies;functional restoration;gamma Globin;Gene Deletion;Gene Mutation;gene replacement;gene therapy;Genes;genome editing;Globin;Grant;Guide RNA;Health;Hematopoietic;hematopoietic stem cell differentiation;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Hemoglobin;Hemoglobin H;Hemoglobinopathies;High Pressure Liquid Chromatography;Human;Immigration;Immunodeficient Mouse;improved;in utero;In Vitro;in vivo;Initiator Codon;innovation;insertion/deletion mutation;Institution;International;Intrauterine Blood Transfusion;iron chelation therapy;Length;Lentivirus Vector;Mediating;Medical;Mendelian disorder;Morbidity - disease rate;Mus;Mutate;Neurological outcome;Nucleic Acid Regulatory Sequences;Outcome;Oxygen;Patients;Pattern;Phase I/II Clinical Trial;postnatal;pre-clinical;Production;Proteins;PTPRC gene;reconstitution;Regimen;Registries;repaired;restoration;Safety;Scheme;Severity of illness;Site;southeast Asian;Specificity;Stem cell transplant;Testing;Toxic effect;Transfusion;Transgenes;Transplantation;treatment strategy;vector;Work;zeta Globin

PROJECT_TITLE: Developing gene therapy strategies to treat alpha thalassemia

STUDY_SECTION: GDD

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


NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Gene Therapy;Genetics;Liver Disease;Orphan Drug;Rare Diseases

ORG_CITY: DURHAM

ORG_DEPT: PEDIATRICS

ORG_NAME: DUKE UNIVERSITY

PHR: PROJECT NARRATIVE Transgene silencing has been identified as a clinical hurdle for long-term AAV gene therapy approaches. We will dissect vector genome silencing mechanisms and explore potential therapeutic strategies in a novel human liver chimeric mouse model using xenografted human hepatocytes from patients with metabolic liver disease.

PI_NAMEs: ASOKAN, ARAVIND ;BISSIG, KARL-DIMITER  (contact)

PROGRAM_OFFICER_NAME: BURGESS-BEUSSE, BONNIE L

PROJECT_TERMS: Acute;adeno-associated viral vector;Advisory Committees;Animal Model;Binding;Biodistribution;Biological Assay;Biology;canine model;Capsid;Cells;Clinical;clinical translation;Clinical Trials;clinically relevant;Complex;CRISPR-mediated transcriptional activation;Data;Deposition;derepression;design;Development;Disease;Dose;Engineering;Enzymes;Epigenetic Process;Event;experience;Failure;Gene Expression;Gene Expression Profile;gene product;Gene Silencing;gene therapy;gene therapy clinical trial;gene-targeted therapy;Genetic Transcription;Genome;Genome Components;genome editing;Genomic DNA;genotoxicity;Glycogen storage disease type II;Hemophilia A;Hemophilia B;Hepatocyte;Hepatocyte transplantation;Hepatolenticular Degeneration;Hepatotoxicity;Histone Deacetylase Inhibitor;Histones;Human;human disease;humanized mouse;Immune response;Implant;In Vitro;in vivo;Individual;innovation;Integration Host Factors;knock-down;Knockout Mice;Lentivirus Vector;Liver;Liver diseases;Maps;Mediating;meetings;Metabolic;Methylation;methylmalonic aciduria;Modeling;Molecular;mouse model;Mouse Strains;Mus;nonhuman primate;novel;Organ;Ornithine carbamoyltransferase deficiency;Patients;Pattern;pharmacologic;Pre-Clinical Model;prevent;Process;promoter;Promoter Regions;Reporting;Repression;response;restoration;Role;Serotyping;Serum;small hairpin RNA;Steroids;T cell response;Therapeutic;therapeutic target;therapeutic transgene;transcription factor;transgene expression;Transgenes;Tropism;uptake;Urea cycle disorders;Variant;vector;vector genome;Viral;Viral Genes;Viral Genome;viral genomics;Viral Vector;Virus Receptors;Work;Xenograft procedure

PROJECT_TITLE: Dissecting AAV silencing in humanized mice


NIH_SPENDING_CATS: Genetics

ORG_CITY: LA JOLLA

ORG_NAME: LA JOLLA INSTITUTE FOR IMMUNOLOGY

PHR: Project Narrative T cells are key players in immune responses that are essential to protect the host against a variety of pathogens and cancers. In some cases, their uncontrolled activity can also lead to pathologies such as inflammatory or autoimmune diseases. It is thus essential to understand the mechanisms underlying their activation and regulation. This activation is mediated by the T cell receptor, which when triggered, leads to a cascade of intracellular events involving several molecules. In this proposal we will investigate how the molecule, THEMIS and the mechanisms it employs, regulate the function of T cells.

PI_NAMEs: CHEROUTRE, HILDE MC (contact)

PROGRAM_OFFICER_NAME: PRABHUDAS, MERCY R

PROJECT_TERMS: Address;Affect;Anatomy;Atopic Dermatitis;Autoimmune Diseases;Automobile Driving;Binding;Binding Sites;Biology;Celiac Disease;Cell Nucleus;Cellular biology;Chromatin;conditional knockout;CRISPR/Cas technology;Cytoplasm;Data;Defect;design;Development;Disease;DNA Footprint;Dominant-Negative Mutation;EGF gene;Evaluation;Event;experimental study;Generations;Government;Homeostasis;Human;Immune response;Impairment;Infection;Inflammatory;Insulin-Like Growth Factor I;Knockout Mice;loss of function;Malignant Neoplasms;MAPK1 gene;Mature T-Lymphocyte;Mediating;Memory;Mouse Strains;Multiple Sclerosis;Mus;mutant;Mutant Strains Mice;Mutate;Nuclear;Nuclear Export;pathogen;Pathogenesis;Pathology;Pathway interactions;Persons;Phenotype;Play;Proteins;Regulation;Risk;Role;Signal Pathway;Signal Transduction;Signaling Molecule;T-Cell Development;T-Cell Receptor;T-Lymphocyte;Testing;thymocyte;Thymocyte Development;Thymus Gland;tool;transcriptome;Transgenes

PROJECT_TITLE: The Role of Cytoplasmic and Nuclear THEMIS in Immature and Mature T cells


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

PHR: NARRATIVE Although the viruses of bacteria and archaea (phage) are touted to be the most abundant organisms on Earth and research with bacteriophage has played and continues to play a central role in the development of molecular biology and biotechnology, there remain fundamental unanswered questions about the evolution of these viruses and their contribution to the ecology and evolution of their hosts. The proposed jointly theoretical and experimental study of the population biology and evolution of bacteriophage will address and answer three classes of questions: 1- Existence conditions; under what conditions will phage be maintained and regulate the densities of these host populations? 2- Horizontal versus vertical transmission: under what conditions will natural selection favor the evolution and maintenance of a lysogenic rather than a purely lytic mode of phage replication? 3- The evolution and maintenance of adaptive immunity: under what conditions will selection mediated by virulent and temperate phage lead to the evolution of and maintenance of CRISPR-Cas - mediated adaptive immunity? !

PI_NAMEs: LEVIN, BRUCE RICHARD (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: adaptive immunity;Address;Archaea;Bacteria;Bacterial Infections;Bacteriophages;Basic Science;Biology;Biotechnology;Clustered Regularly Interspaced Short Palindromic Repeats;Computer Simulation;design;Development;Domestic Animals;Ecology;Escherichia coli;Evolution;experimental study;Genetic;Human;Investigation;Lead;Liquid substance;Lytic;Maintenance;Mathematics;Mediating;Modeling;models and simulation;Molecular Biology;Natural Selections;Organism;outbreak control;Parameter Estimation;pathogenic bacteria;Planet Earth;Play;Population;Population Biology;Population Dynamics;Population Study;Program Evaluation;Property;Pseudomonas aeruginosa;Pseudomonas syringae;Research;resistance mechanism;Role;Solid;Staphylococcus aureus;Structure;Surface;System;Testing;Theoretical Studies;theories;transmission process;Vertical Transmission;Virulent;Virus

PROJECT_TITLE: Theoretical and Experimental Studies of the Population and Evolutionary Dynamics of Bacteria and Bacteriophage.

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


NIH_SPENDING_CATS: Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: SANTA BARBARA

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA BARBARA

PHR: Narrative We are studying an organism in which a natural transplantation reaction mediates the transmission of stem cells between two individuals, which then compete to contribute to regeneration. Our studies will continue to provide novel insights into the mechanisms which underlie these diverse processes, and have major significance, from preventing a rejection reaction after transplantation, to understanding how cancer cells outcompete normal cells for resources and growth. In the organism we study, the interaction between transplantation and stem cells in many ways resembles how humans accept or reject bone marrow transplants, but in a simplified fashion that provides opportunities for novel approaches to study these questions that cannot be done in other species.

PI_NAMEs: DE TOMASO, ANTHONY W (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: autocrine;Award;Biological;Biological Assay;Biological Models;Blood Vessels;Bone Marrow Transplantation;cancer cell;Cardiovascular system;cell regeneration;Cells;Chordata;Endocrine;Event;follow-up;Funding;Gene Modified;Germ cell tumor;Germ Lines;germline stem cells;Goals;Grant;Growth;Homing;Human;Immunity;Immunology;Individual;innovation;insight;Mediating;Molecular;Natural regeneration;Normal Cell;novel;novel strategies;Organism;Peripheral;Phenotype;prevent;Process;programs;Property;Reaction;Regenerative response;Research;Resources;response to injury;Specificity;stem cell biology;stem cell niche;stem cells;tissue regeneration;transmission process;Transplantation;Work

PROJECT_TITLE: Allorecognition, parasitic stem cells and regeneration in a basal chordate

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


ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: This project examines the phytochromes, a superfamily of photoreceptors that can detect to a broad range of colors and can transmit that information to the cell to control many aspects of biology. Plant phytochromes are a major stumbling block in improving agricultural yield by mediating the shade avoidance response caused by competition for light among neighboring plants, while their bacterial relatives have proven a valuable source of imaging reagents for biomedical research and of photosensory reagents for synthetic control of cellular processes with light. Work under this project will provide new insight into color tuning, the usage of light energy, the integration of light with signals such as temperature and pH, and the transmission of information within these photoreceptors and to the rest of the cell.

PI_NAMEs: LAGARIAS, JOHN CLARK (contact)

PROGRAM_OFFICER_NAME: SALVADOR MORALES, CAROLINA

PROJECT_TERMS: Agriculture;Algae;Bacteria;Basic Science;Bilin;Biological Process;Biology;biomedical imaging;Biomedical Research;Biophysical Process;Cell Physiology;Cells;chromophore;Color;Detection;Development;Environment;Evolution;Exhibits;Family member;Family Process;Flowers;Fluorescence;Food;Genes;Germination;Goals;Human;Image;Imaging Device;improved;insight;interest;Interphase Cell;knowledge base;Learning;Light;LIGHT protein;Mediating;member;Metabolism;Methods;Microbial Biofilms;Mission;Molecular;National Institute of General Medical Sciences;new technology;Photoreceptors;phyA phytochrome;Phytochrome;plant growth/development;Plants;Population;Process;promoter;Protein Family;Proteins;Reagent;Reporting;Research;response;Signal Transduction;Source;synthetic biology;System;Systems Biology;Targeted Research;Temperature;Tetrapyrroles;Tissues;transmission process;ultraviolet;Work

PROJECT_TITLE: Understanding and leveraging molecular diversity within the phytochrome superfamily

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_CITY: GALVESTON

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

PHR: PROJECT NARRATIVE Overdose deaths involving cocaine continue to escalate while cocaine use disorder continues to present a disturbing chronic health problem and a heavy individual and societal burden in the United States. Medications to promote the success of psychosocial treatment are needed to mitigate these harms to human health. Our preclinical research focuses on neural pathways and druggable targets that impact the “final common pathway” for drug-seeking and the results of this research will inform not only the addiction-related biology of the brain but will ultimately chart the course to new therapeutics for treatment of cocaine use disorder.

PI_NAMEs: CUNNINGHAM, KATHRYN A.;HOMMEL, JONATHAN DEAN (contact)

PROGRAM_OFFICER_NAME: BERTON, OLIVIER

PROJECT_TERMS: Abstinence;addiction;Affect;Affinity;Anatomy;Behavior;behavioral economics;Biological Assay;Biology;Brain;Brain region;Chronic;Cocaine;cocaine exposure;cocaine self-administration;cocaine sensitization;cocaine use;Cocaine use disorder;Consumption;COVID-19 pandemic;Data;designer receptors exclusively activated by designer drugs;dorsal raphe nucleus;druggable target;Elements;FDA approved;Foundations;G-Protein-Coupled Receptors;gamma-Aminobutyric Acid;Globus Pallidus;Goals;Health;Human;Hyperactivity;Incentives;Individual;Infusion procedures;innovation;Intake;knock-down;Learning;Ligands;Link;Maps;Mass Spectrum Analysis;Mediating;Medical;Microdialysis;Modeling;Motivation;motivational processes;neural;neural circuit;Neural Pathways;Neuroanatomy;Neuromedin U;neuromedin U receptor;Neurons;neuropathology;Neuropeptides;neurotransmitter release;Neurotransmitters;novel;novel therapeutics;Nucleus Accumbens;Outcome;Output;overdose death;Pathway interactions;Peptides;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;pre-clinical research;presynaptic;Protocols documentation;psychosocial;Publishing;Rattus;receptor;Relapse;Research;Resources;Rewards;Rodent Model;Role;Self Administration;sex as a biological variable;Signal Transduction;Structure;Substance Use Disorder;success;Synapses;System;Technology;Testing;Texas;theories;Therapeutic;United States;Universities;ventral visual stream;Viral Vector

PROJECT_TITLE: Novel Addiction Neurocircuits in Cocaine Taking

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


NIH_SPENDING_CATS: Hematology;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: MILWAUKEE

ORG_NAME: VERSITI WISCONSIN, INC.

PHR: PROJECT NARRATIVE Signals communicating the need to maintain balanced blood production and aged blood cell removal must be correctly conveyed to the marrow's hematopoietic stem and progenitor cells and covey proper blood cell removal signals. These molecular mechanisms are intensely studied to provide new insight into the potential for novel therapeutic approaches in blood disorders, specifically affecting platelet and red blood cell counts. The proposed work will yield a transformative understanding of how liver-produced factors contribute to maintaining red blood cell production in the bone marrow at a steady state and provide new insight into novel therapeutic approaches for patients with blood disorders.

PI_NAMEs: HOFFMEISTER, KARIN MARIA (contact)

PROGRAM_OFFICER_NAME: WARREN, RONALD Q

PROJECT_TERMS: Acetylgalactosamine;Affect;aged;Attenuated;Binding;Biochemical;Blood;Blood Cells;Blood Platelets;Bone Marrow;bone marrow mesenchymal stem cell;Calgranulin A;Calgranulin B;Carbohydrates;Cell Count;Cells;Communication;cytokine;Data;Defect;Development;Disease Progression;Dysmyelopoietic Syndromes;Epidermal Growth Factor Receptor;ERBB2 gene;ERBB3 gene;ErbB4 gene;Erythroblasts;Erythrocytes;Erythroid;erythroid differentiation;Erythropoiesis;Excision;extracellular;Family;Galactose;Generations;Genetic;genetic approach;genome wide association study;Hematological Disease;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Hemoglobin concentration result;Hepatic;Hepatocyte;Homeostasis;Human;Impairment;In Vitro;Inflammation;Inflammatory;inhibitor;insight;Investigation;Island;Knockout Mice;Knowledge;Leukocyte L1 Antigen Complex;Ligands;Liver;Macrophage;Maintenance;Marrow;Measures;Mediating;Megakaryocytes;member;Mesenchymal Stem Cells;mesenchymal stromal cell;Modeling;Molecular;mouse model;Mus;Myelodysplastic/Myeloproliferative Disease;neuregulin-4;neutrophil;novel therapeutic intervention;Patients;Plasma;Production;progenitor;programs;receptor;Receptor Protein-Tyrosine Kinases;Recombinants;Red Blood Cell Count;Role;S100 Calcium Binding Protein;S100 Proteins;S100A8 gene;S100A9 gene;Signal Transduction;stem cell function;stem cell homeostasis;Stromal Cells;Testing;therapeutic development;Thrombopoiesis;Thrombopoietin;Transcript;transcriptomics;Up-Regulation;Variant;Work

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-VH-C(02)M]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Aging;Biodefense and Related Countermeasures;Bioengineering;Biomedical Imaging;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Infectious Diseases;Physical Injury - Accidents and Adverse Effects

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: NARRATIVE Extensively use of glucocorticoids is a major risk factor for fracture and delayed fracture healing. Given the current COVID infection rate in the US population and the significant number of COVID patients who needed glucocorticoid treatment, a post pandemic surge of fracture and delayed fracture healing is widely anticipated. Except surgical intervention, there is few FDA approved therapy for glucocorticoid-induced delayed fracture healing at present. To address this urgent unmet need, we seek to develop a novel thermoresponsive macromolecular prodrug of Tanshinone IIA (ProGel-TAN) as a highly effective and safe treatment of glucocorticoid-induced delayed fracture healing in this project.

PI_NAMEs: WANG, DONG  (contact)

PROGRAM_OFFICER_NAME: MARQUITZ, ARON

PROJECT_TERMS: Acceleration;Address;Affect;Aftercare;Aging;Alcohol consumption;American;Anabolic Agents;angiogenesis;Animal Model;Anticoagulants;Antiinflammatory Effect;aqueous;Autoimmune Diseases;Autologous;Biodistribution;Biology;Biomechanics;Blood flow;Blood Vessels;bone;Bone callus;bone fracture repair;Bone Injury;bone quality;Bone Transplantation;candidate selection;Cells;Characteristics;Chronic;chronic pain;Clinical;clinical efficacy;Clinical Management;clinical translation;Contrast Media;COVID-19 patient;current pandemic;density;design;Development;Diabetes Mellitus;Disease;Dose;Drug Kinetics;drug release kinetics;effective therapy;Estrogen deficiency;Euthanasia;Event;Exhibits;Exposure to;FDA approved;Femoral Fractures;Femur;Flow Cytometry;Formulation;Fracture;fracture risk;Functional impairment;Glucocorticoids;Goals;healing;Hospitalization;Hydrogels;Immunofluorescence Immunologic;Impaired healing;improved;In Vitro;in vivo;in vivo optical imaging;infection rate;infection risk;Inflammatory;insight;Investments;Label;Lasers;lipophilicity;liquid chromatography mass spectrometry;methacrylamide;microCT;Microfils;Mobility decline;Molecular;Molecular Weight;Monitor;mouse model;Mus;musculoskeletal injury;novel;Operative Surgical Procedures;Orthopedic Surgery;Orthopedics;Osteogenesis;osteogenic;Osteoporosis;Pathologic;Perfusion;Pharmaceutical Preparations;Pharmacology;Pharmacology Study;Phase Transition;Polymers;Population;post-pandemic;Postmenopause;preclinical study;Prednisone;Preparation;Procedures;Process;Prodrugs;Property;Quality of life;Regimen;Research;Resolution;Risk Factors;Safety;Salvia miltiorrhiza;Sampling;SARS-CoV-2 infection;side effect;Site;Skeleton;standard care;Temperature;Testing;Therapeutic Agents;Therapeutic Intervention;Time;Tissues;Tobacco;Tobacco use;Transition Temperature;Treatment Efficacy;Viscosity;Water;water solubility;Weight;X-Ray Medical Imaging

PROJECT_TITLE: Effective local delivery of bone anabolic agent to accelerate the healing of delayed fracture union


NIH_SPENDING_CATS: Brain Disorders;Cardiovascular;Epilepsy;Genetics;Heart Disease;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE Th goal of this project is to develop and validate a transgenic large animal model of Dravet syndrome in which the role of seizures and cardiac arrhythmias in sudden unexpected death in epilepsy (SUDEP) can be investigated. Rabbits more closely replicate the human cardiac action potential compared to mice and provide a complete organism to translate to the clinical setting. If validated, this work will be a significant advance over currently available Dravet syndrome models and will better inform the translatability of neuro-cardiac mechanisms of SUDEP to human disease.

PI_NAMEs: ISOM, LORI L. (contact)

PROGRAM_OFFICER_NAME: SPRIGGS, SHARDELL M

PROJECT_TERMS: Action Potentials;Age;Animal Genetics;Animal Model;Animals;Antisense Oligonucleotide Therapy;Apnea;Arrhythmia;Autonomic Dysfunction;Behavioral;Biological Markers;Brain;Calcium;Cardiac;Cardiac Myocytes;Cardiovascular system;Cause of Death;Cells;Cessation of life;Clinical;clinical diagnosis;clobazam;cohort;Complex;CRISPR/Cas technology;Data;density;Development;Dissection;dravet syndrome;Drug Combinations;effective therapy;Epilepsy;epileptic encephalopathies;Frequencies;Future;gain of function;gene therapy;Generalized seizures;Genes;Genetic;Genetic Models;Goals;Heart;heart innervation;Human;human disease;human induced pluripotent stem cells;human old age (65+);Incidence;induced pluripotent stem cell;insight;Knowledge;Link;loss of function;Michigan;Modeling;mouse model;Mus;nerve supply;Neurons;New Zealand;novel marker;novel therapeutic intervention;Organism;Oryctolagus cuniculus;Patients;Pharmaceutical Preparations;Phase;Phenotype;Physiology;premature;prevent;Rattus;respiratory;Risk;risk variant;Rodent;Role;SCN1A protein;SCN8A gene;Seizures;Sodium;Sodium Channel;stem cell model;success;sudden unexpected death in epilepsy;Testing;Tissues;Transgenic Mice;Transgenic Organisms;Translating;translational model;Translational Research;translational therapeutics;two-dimensional;Universities;Validation;Variant;Video Recording;voltage;Work

PROJECT_TITLE: Development and Validation of a Transgenic Rabbit Model of Dravet Syndrome

STUDY_SECTION: NSD

STUDY_SECTION_NAME: Neurological Sciences and Disorders A Study Section[NSD-A]


ADMINISTERING_IC: AG

ED_INST_TYPE: OTHER SPECIALIZED SCHOOLS

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);Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Cerebrovascular;Dementia;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE This project aims to design, test, and validate an interpretable, trustworthy, and generalizable ML architecture that leverages magnetic resonance imaging (MRI) to estimate brain age accurately. Our efforts will map neuro- anatomic features of MRI-predicted brain ages that reflect accelerated aging observed in mild cognitive impair- ment (MCI) and Alzheimer’s disease (AD). We will synergize our interpretable ML approaches with genome- wide association (GWAS) to (A) find genes associated with the neuroanatomic features in question, (B) identify genetic factors acting on brain aging features that predict MCI/AD diagnosis, and (C) develop and validate a polygenic risk score (PRS) of vulnerability to accelerated brain aging observed in MCI/AD.

PI_NAMEs: IRIMIA, ANDREI  (contact)

PROGRAM_OFFICER_NAME: YAO, ALISON Q

PROJECT_TERMS: 10 year old;Acceleration;Adult;Affect;Age;age acceleration;age related changes;Aging;aging brain;aging related;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease patient;Alzheimer's disease risk;Anatomy;Architecture;biobank;Black Box;Blood - brain barrier anatomy;Blood Cells;Brain;brain magnetic resonance imaging;Brain region;cerebral microbleeds;Chronology;Clinical;Cognition;Cognitive;cognitive function;cohort;Communities;Data Set;dementia risk;design;Disease;DNA Methylation;Ensure;Environment;Epigenetic age;epigenetic aging;Ethnic Origin;Exhibits;explainable machine learning;Extravasation;Genes;Genetic;genetic variant;genome wide association study;Genotype;Geometry;Image;Impaired cognition;Individual;insight;Logic;Machine Learning;Magnetic Resonance Imaging;Maps;Measures;Methods;methylation pattern;mild cognitive impairment;neural;Neuroanatomy;Neurodegenerative Disorders;neuroimaging;Neuropsychology;novel;Pathologic;pathological aging;Pattern;Persons;Phenotype;polygenic risk score;pre-clinical;predictive modeling;Predisposition;Process;Race;resilience;Sampling;sex;Specificity;synergism;Techniques;Testing;Training;trustworthiness;Validation;Whole Blood

PROJECT_TITLE: Interpretable machine learning to synergize brain age estimation and neuroimaging genetics

STUDY_SECTION: EITN

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


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering

ORG_CITY: ARLINGTON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF TEXAS ARLINGTON

ORG_STATE: TX

PHR: Project Narrative A three-tiered approach is being implemented at the University of Texas at Arlington to transform our biomedical engineering design experience through a program that will facilitate team-based hands-on experiential learning and mentorship that spans the undergraduate degree plan. We will specifically implement new components of a team service-learning design course at the sophomore level, a summer clinical immersion program with local hospitals and emergency medical services at the junior level, and a team-centered workshop led by local industry experts on the translation and commercialization of medical devices to augment the senior design experience. Through these enhancements to our program, we target the development of fundamental skills to prepare our engineering students for serving in the biomedical workforce and entrepreneurship in the biomedical industry.

PI_NAMEs: CHO, MICHAEL ;JAWORSKI, JUSTYN  (contact)

PROGRAM_OFFICER_NAME: GUTEKUNST, DAVID JOSEPH

PROJECT_TERMS: Active Learning;Address;Advanced Development;Area;Awareness;Bachelor's Degree;Biomedical Engineering;Businesses;career;Characteristics;Clinical;clinically relevant;Clinics and Hospitals;cohort;commercialization;Communities;community engagement;Community Health;community involvement;community partners;Complex;Country;Critical Thinking;design;Development;Device or Instrument Development;Devices;early experience;Education;Educational Curriculum;Educational workshop;Emergency medical service;empowerment;Engineering;engineering design;Entrepreneurship;expectation;experience;Exposure to;Face;Feedback;Goals;Health;Hospitals;Human;ideation;Immersion;improved;Industry;innovation;Intuition;Joints;Knowledge;leadership development;learning engagement;learning outcome;lens;manufacture;Marketing;Medical;Medical center;Medical Device;Medical Technology;Medicine;Mentors;Mentorship;Minority Groups;Minority-Serving Institution;next generation;Occupations;Population;Population Growth;Process;programs;Public Health;Regulatory Affairs;Regulatory Pathway;Research;Risk;Science;Series;service learning;Services;skill acquisition;skills;social;social engagement;Social Responsibility;Societies;student participation;Student recruitment;Students;Technology;Texas;Training;Translating;Translations;undergraduate student;Underrepresented Minority;underrepresented minority student;underserved area;Universities;Work

PROJECT_TITLE: Enhancing Undergraduate Bioengineering Education through Engaged Service Learning, Clinical Immersion, and Entrepreneurship


NIH_SPENDING_CATS: Biotechnology;Genetics;Muscular Dystrophy;Myotonic Dystrophy;Neurosciences;Orphan Drug;Rare Diseases

PHR: The identification of candidate drugs that halt or slow down the progression of Myotonic Dystrophy Type 1, a genetic disorder with no cure, is urgently needed. This project seeks to identify novel potent chemical compounds of therapeutic value for this disease.

PI_NAMEs: COMAI, LUCIO  (contact);REDDY, SITA

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: 3' Untranslated Regions;absorption;Affect;Antisense Oligonucleotide Therapy;Antisense Oligonucleotides;autosome;Biochemical;Biological Assay;Biological Products;Biology;Blood - brain barrier anatomy;Brain;Budgets;candidate identification;Cells;Central Nervous System;Chemicals;Clinical Trials;comparative;Complex;CUG repeat;Cyclic AMP-Dependent Protein Kinases;Data;Defect;design;Development;Disease;Dose;drug candidate;Drug Combinations;drug development;effective therapy;Exhibits;Genes;Genetic Diseases;In Vitro;in vivo;in vivo evaluation;inhibitor;insight;Lead;Libraries;Link;Literature;Measures;Mediating;Messenger RNA;Molecular;mouse model;Muscle;mutant;Myoblasts;Myopathy;Myotonic Dystrophy;Myotonic dystrophy type 1;novel;overexpression;Pathologic;Pathology;Patients;Penetrance;Permeability;Pharmaceutical Preparations;Phenotype;Physiological;Play;Probability;Protein Family;Proteins;prototype;Publishing;response;RNA;RNA Splicing;Role;Safety;screening;Skeletal Muscle;small molecule;small molecule therapeutics;System;Testing;Therapeutic;therapeutic candidate;therapeutic target;Time;Toxic effect;Transcript;Transgenic Mice;Transgenic Organisms

PROJECT_TITLE: Small molecule therapeutics for myotonic dystrophy type 1

STUDY_SECTION: TAG

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


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

ORG_CITY: RICHARDSON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

PHR: PROJECT NARRATIVE: Extinguishing the drug-cue associations that trigger craving and relapse is an important goal in the treatment of substance use disorders. The experiments in this project will use an animal model of cocaine-seeking to study maladaptive changes in synaptic plasticity that drive drug-seeking and they will determine the mechanisms through which vagus nerve stimulation can reverse these neuronal adaptations to facilitate extinction and reduce relapse.

PI_NAMEs: KROENER, SVEN  (contact)

PROJECT_TERMS: activity marker;addiction;Adjuvant;Affect;AMPA Receptors;Amygdaloid structure;Animal Model;Behavior;Behavioral;behavioral response;Brain-Derived Neurotrophic Factor;Cells;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Cocaine;cocaine seeking;cocaine self-administration;Complement;craving;CRISPR/Cas technology;Cues;Data;drug seeking behavior;Drug usage;Electrophysiology (science);Epilepsy;experimental study;Exposure to;Extinction;FDA approved;Fright;Glutamate Receptor;glutamatergic signaling;Glutamates;Goals;hippocampal pyramidal neuron;Hippocampus;Human;in vivo;knock-down;Label;Laboratories;Learning;learning extinction;maladaptive behavior;Mediating;Memory;Mental Depression;Morphology;neuroadaptation;Neuromodulator;Neurons;Neurotrophic Tyrosine Kinase Receptor Type 2;novel;Nucleus Accumbens;optogenetics;Output;patch clamp;Pathway interactions;Pharmaceutical Preparations;Physiological;postsynaptic;Prefrontal Cortex;presynaptic;prevent;Process;protective effect;Rattus;receptor function;Relapse;relapse prevention;relapse risk;release factor;Research;Resolution;Rewards;Shapes;Stimulus;Stress;Substance Use Disorder;substance use treatment;Synapses;Synaptic plasticity;Testing;Time;Training;transmission process;vagus nerve stimulation;voltage clamp

PROJECT_TITLE: Vagus nerve stimulation modulates synaptic plasticity in the rat prefrontal cortex during the extinction of drug-seeking


NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Cardiovascular;Cerebrovascular;Clinical Research;Down Syndrome;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Prevention;Stroke

ORG_CITY: LOS ANGELES

ORG_NAME: CHILDREN'S HOSPITAL OF LOS ANGELES

PHR: Project Narrative: Down syndrome (DS) is one of the most common genetic disorders with a prevalence of 1 per 700 liveborn infants in the United States and is associated with an increased risk of developing cerebrovascular disorders (CeVD), which commonly present with stroke as the first evidence of disease. The proposed research will result in the creation of a validated, non-invasive, low-cost, biometric screening tool for young persons with DS in order to address the pressing need of reliable screening of CeVD in at-risk individuals. This proposal presents a five-year research career development program with training that will position me with a unique set of interdisciplinary skills to enable transition to independence as a physician-scientist to study the prediction and prevention of CeVD in persons with DS.

PI_NAMEs: SANTORO, JONATHAN DOUGLAS (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: Acceleration;Accounting;Active Learning;Address;Age;aged;Architecture;Area;Bioinformatics;Biological Markers;biomedical informatics;Biometry;Blood Pressure;blood pressure elevation;blood pressure reduction;Blood Vessels;Brain;career;career development;Caring;CCL2 gene;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;Child;Childhood;Chronic;chronic inflammatory disease;Clinical Trials;Clinical Trials Design;cohort;Communication;comparison control;Competence;cost;Data;Data Analyses;Deposition;design;Development;Development Plans;Diagnosis;Disease;Disease Pathway;Down's Syndrome;Early Diagnosis;Early identification;Early Intervention;early screening;Edema;Educational workshop;Ensure;Epidemiology;Etiology;experience;feasibility research;Functional disorder;Funding;Genetic Diseases;Gliosis;Goals;Granulocyte-Macrophage Colony-Stimulating Factor;Head and neck structure;Health;Health Sciences;Healthcare;Height;Hemosiderin;Home;Hypertension;Hypotension;Image;Immune;improved;Incidence;Individual;Infant;Inflammation;Inflammatory;Institution;Interferon Type II;interleukin-22;Interleukin-6;Investigation;K-Series Research Career Programs;Knowledge;Learning;Link;Location;Los Angeles;Magnetic Resonance Imaging;Measurement;Measures;Mentors;Mentorship;Metabolic dysfunction;Modality;Morbidity - disease rate;mortality;Moyamoya Disease;Neck;Neurocognitive;neurocognitive test;neurodevelopment;neuroimaging;Neurologic;Neurologic Symptoms;Patients;Persons;PGF gene;Physicians;population based;Positioning Attribute;predictive marker;Prevalence;prevent;Prevention;Program Development;prospective;Prospective Studies;Publishing;Regression Analysis;Reproducibility;Research;Research Personnel;response;Retrospective Studies;Risk;Risk Assessment;Role;Scientist;screening;Screening procedure;Secondary to;sex;skills;Standardization;Stenosis;Stroke;systemic inflammatory response;Techniques;Therapeutic Intervention;Time;TNF gene;tool;Training;Transcranial Doppler Ultrasonography;Ultrasonography;United States;United States National Institutes of Health;Vascular Cell Adhesion Molecule-1;Vascular Diseases;Vascular Endothelial Growth Factors;vascular inflammation;Weight;Work

PROJECT_TITLE: Non-invasive biometric screening for cerebrovascular disorders in persons with Down syndrome.

STUDY_SECTION: MPOR

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


ORG_CITY: Boulder

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it dissects the mechanisms of action of molecules that go awry in cancer and other human diseases. The work in this proposal will examine previously unrecognized molecular processes which are central to the regulation of human cells. Detailed knowledge of these processes will provide information that can be used to develop new therapeutics to treat cancer and other diseases.

PI_NAMEs: AHN, NATALIE G. (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Address;Affinity;cell motility;Cells;Complex;directional cell;Disease;Dissection;Human;human disease;inhibitor;Knowledge;Laboratories;Malignant Neoplasms;MAPK1 gene;Microscopic;Mitogen-Activated Protein Kinases;Molecular;Motion;Names;novel therapeutics;Organelles;Phosphorylation;Process;Protein Kinase;Proteins;Public Health;Regulation;Research;Signal Transduction;Structure;Work

PROJECT_TITLE: Molecular and Cellular Dynamics in Mammalian Signal Transduction


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

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

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative In this project we describe the “Assemblatron”, a system that optimizes the “Yeast assembly” process by which huge DNA molecules are designed and built. We will develop a system in which one person can assemble 1-2 million “DNA letters” worth of DNA into very large pieces, representing 10-20 pieces, each more than 100,000 DNA letters long, representing a 10-20 fold increase in productivity.

PI_NAMEs: BOEKE, JEF D (contact)

PROGRAM_OFFICER_NAME: GILCHRIST, DANIEL A

PROJECT_TERMS: Affect;Agriculture;Algorithms;Area;Automation;Bacterial Artificial Chromosomes;Biological Assay;biological research;Biomedical Research;Bypass;Characteristics;Circular DNA;cost;dark matter;design;Development;Devices;Diagnosis;disorder prevention;DNA;Dryness;Ecosystem;Environment;Environment Design;Environmental Science;Evolution;Excision;Exonuclease;Frequencies;Genes;Genomics;Genotype;Goals;homologous recombination;Human;improved;International;Length;Letters;Link;Machine Learning;Measures;Mentors;Methods;Modification;National Human Genome Research Institute;Nucleic Acids;Oligonucleotides;Persons;Probability;Process;Productivity;programs;Protocols documentation;rapid technique;remediation;Reproducibility;Research;Research Personnel;Series;Short Tandem Repeat;Software Design;Source;Structure;synthetic construct;synthetic genomics;synthetic nucleic acid;System;Techniques;Testing;Transcriptional Regulation;Tube;Untranslated RNA;vector;Work;yeast genome;Yeasts

PROJECT_TITLE: The Assemblatron