ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

PHR: PROJECT NARRATIVE CRISPR-associated nucleases have furnished transformative biomedical technologies. We propose to develop methods and reagents to enhance the capabilities of these CRISPR-based technologies. PHS 398/2590 (Rev. 1 06/09) Continuation Format Page

PI_NAMEs: CHOUDHARY, AMIT  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Acetyltransferase;Affinity;base;Base Pairing;Binding;Biomedical Technology;Cells;Charge;Chemicals;chemoproteomics;Chromosomal translocation;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;CRISPR/Cas technology;Cysteine;Deacetylase;Deoxyribonuclease I;Development;DNA;DNA Binding;Dose;endonuclease;Endowment;Engineering;Enzymes;epigenome editing;esterase;Esterification;gene repression;gene therapy;Gene Therapy Agent;genetic approach;Genetic Transcription;Genome;genome editing;Genome engineering;genomic locus;Genomics;genotoxicity;Guide RNA;Hereditary Disease;HIV;Hydrophobicity;Image;Impairment;improved;inhibitor;Laboratories;Light;Lysine;Mammalian Cell;Methods;mimetics;Modification;Muscular Dystrophies;nanomolar;nuclease;Overdose;Paint;Pathology;Performance;Permeability;personalized approach;Proteins;Proteome;Reagent;Reporting;Repression;Ribonucleases;Scheme;Site;small molecule;small molecule inhibitor;Specificity;Structure;Structure-Activity Relationship;System;targeted nucleases;Technology;Time;Toxic effect;Transcription Coactivator;Transcription Repressor;Transcriptional Activation;Vision Disorders

PROJECT_TITLE: Chemical approaches for precision genome editing

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


ADMINISTERING_IC: HL

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Lung;Lymphatic Research;Rare Diseases;Tuberous Sclerosis;Women's Health Research

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Narrative Lymphangioleiomyomatosis is a low grade neoplasm that causes progressive lung destruction, lung cyst formation, and respiratory failure due to mutations in TSC2. In this proposal, we will determine whether mutations in other mTOR pathway and/or MITF family genes cause sporadic LAM, second, we will determine whether TSC2 mutations in plasma cell free DNA can be a biomarker of sporadic LAM, and at the same time search for generalized mosaicism in sporadic LAM patients who have singleton features of TSC in addition to LAM and third, we will examine the role of a new LAM gene, NR2F2, in LAM development through a series of genetic and epigenetic analyses.

PI_NAMEs: KWIATKOWSKI, DAVID J. (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: Adult;Affect;AKT1 gene;AKT2 gene;AKT3 gene;Alleles;Allelic Imbalance;analog;Angiofibroma;Angiomyolipoma;apoAI regulatory protein-1;Bilateral;Binding;Biological Assay;Biological Markers;Biopsy Specimen;Blood;cell free DNA;Cell Line;cell type;Cells;ChIP-seq;Chromosome 15;Clinical;clinical center;clinical phenotype;Cyst;Data;Detection;Development;Diagnosis;diagnostic criteria;DNA;Enhancers;Epigenetic Process;Event;Face;Family member;FRAP1 gene;Freezing;Frequencies;Gene Family;Gene Frequency;Genes;Genetic;Genetic Screening;Genetic Transcription;genome wide association study;genome-wide;Growth;high standard;Human;Individual;inhibitor;Lesion;Lung;lung lesion;Lung Lymphangioleiomyomatosis;Lymphangioleiomyomatosis;Massive Parallel Sequencing;Mosaicism;Mutation;Mutation Analysis;Mutation Detection;Naphthalene;Neoplasms;new technology;new therapeutic target;novel;novel marker;overexpression;Pathogenesis;Pathologic;Pathway interactions;Patients;Plasma Cells;Population;Prognosis;Renal Angiomyolipoma;Reporting;Research Personnel;Respiratory Failure;Role;Sampling;Series;Skin Manifestations;Somatic Mutation;Specimen;Subgroup;Testing;TFE3 gene;Time;transcription factor;transcriptome sequencing;treatment response;Tretinoin;TSC1 gene;TSC1/2 gene;TSC2 gene;United States National Institutes of Health;variant detection

PROJECT_TITLE: Genetics of LAM

STUDY_SECTION: LIRR

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


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: Boston

ORG_DEPT: CHEMISTRY

ORG_NAME: TUFTS UNIVERSITY MEDFORD

PHR: The Kritzer lab addresses foundational problems in drug discovery. In this MIRA project, we describe new innovations including novel compounds that block key proteins implicated in late-stage cancers, novel classes of compounds that can degrade any cellular protein on demand, and novel methods to understand how large- molecule therapeutics enter cells and how to design them to enter cells more efficiently.

PI_NAMEs: KRITZER, JOSHUA A (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Address;Adopted;Algorithm Design;Area;Autophagocytosis;Binding;Biological Assay;cell type;Cells;Cellular biology;chemotherapy;Chimera organism;CRISPR screen;Cytosol;Data;Degradation Pathway;design;Disease;DNA Damage;drug development;drug discovery;Endosomes;Genetic;Human;inhibition of autophagy;inhibitor;innovation;Kinetics;Learning;Malignant Neoplasms;Measures;Mediating;Methods;Modeling;Molecular Evolution;novel;Penetration;Protac;protein degradation;Protein Family;protein protein interaction;Proteins;research and development;screening;Series;small molecule inhibitor;stapled peptide;Structure;Testing;Therapeutic;Time;Work

PROJECT_TITLE: Developing Autophagy-Targeting Chimeras and Optimizing Cell Penetration of Large-Molecule Therapeutics


ADMINISTERING_IC: AG

ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: The most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two progressive neurodegenerative disorders, is a repeat expansion mutation in an intron of the gene C9orf72. The G4C2 motif is repeated hundreds or thousands of times in affected cells, and the repeat expansion RNA accumulates in the nucleus and contributes to ALS and FTD pathogenesis. Understanding the composition of the RNA that accumulates and the mechanisms that control its degradation will suggest methods to accelerate its decay and perhaps new therapeutic strategies.

PI_NAMEs: SHEHATA, SORAYA I (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: Acceleration;Adenosine;Affect;burden of illness;c9FTD/ALS;C9ORF72;Cell Nucleus;Cells;Cytoplasm;Degradation Pathway;design;Development;Dipeptides;Disease;Enzymes;Eukaryotic Cell;Excision;Exonuclease;exosome;Fellowship;Fluorescent in Situ Hybridization;frontotemporal lobar dementia amyotrophic lateral sclerosis;Future;Genes;Genetic;Goals;Inherited;Introns;Knowledge;Learning;Methods;Modification;mRNA Precursor;Mutate;Mutation;Neurodegenerative Disorders;Neurons;neurotoxicity;novel therapeutic intervention;Nuclear;Oligonucleotides;Pathogenesis;Pathologic;Patients;Persons;Phosphodiesterase I;posttranscriptional;prevent;Process;Proteins;recruit;Resistance;response;RNA;RNA Decay;RNA Degradation;RNA Sequences;RNA Stability;RNA-Binding Proteins;Structure;Tail;Testing;Therapeutic;Therapeutic Intervention;Toxic effect;Translating;Translations;Ubiquitination;Untranslated RNA;Uridine;Work

PROJECT_TITLE: Understanding and Manipulating the Degradation of the C9orf72 Repeat Expansion RNA

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F08-M(20)L]


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: HOUSTON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: PROJECT NARRATIVE Insulin resistance often reflects an inability of white adipose tissue (WAT) to consistently respond to nutrient demands. The enzyme aspartoacylase (ASPA) is involved in lipid synthesis and is highly expressed in white adipose tissue, though its importance outside the brain remains unknown. My preliminary results suggest ASPA plays a prominent role in adipocyte differentiation and lipid storage within white adipose tissue; thus, this research seeks to define the function of ASPA in WAT and understand how its expression contributes to energy balance.

PI_NAMEs: FELIX, JESSICA BESERRA (contact)

PROGRAM_OFFICER_NAME: BODDIE, THOMAS ARTIS

PROJECT_TERMS: Acetates;Acetyl Coenzyme A;adipocyte differentiation;Adipocytes;Adipose tissue;Adult;Advanced Development;Affect;Aspartate;Aspartoacylase;Biological Assay;Brain;Canavan Disease;carbohydrate metabolism;Cardiovascular Diseases;career development;Cells;Chronic;Citric Acid Cycle;combat;comorbidity;Competence;Coupled;CRISPR/Cas technology;Critical Thinking;Data;defined contribution;Deposition;Differentiated Gene;energy balance;Energy Metabolism;Environment;Enzymes;Epidemiology;Experimental Designs;extracellular;Fatty acid glycerol esters;Flow Cytometry;Gene Expression;Generations;Genes;Goals;Growth;High Fat Diet;histone modification;Hormone secretion;Human;Hyperglycemia;Hypertrophy;In Vitro;in vivo;Inflammation;insight;Institution;Insulin Resistance;insulin sensitivity;Knock-out;Knockout Mice;Label;Learning;Link;lipid biosynthesis;lipid metabolism;Lipids;Liver;loss of function mutation;Mass Spectrum Analysis;Medical;Mentors;Metabolic;metabolic phenotype;Metabolism;metabolomics;Methods;Molecular;Morphology;mortality risk;mouse model;Mus;Myelin;myelin degeneration;N-acetylaspartate;Non-Insulin-Dependent Diabetes Mellitus;Nucleotide Biosynthesis;Nutrient;obese person;Obesity;Oligodendroglia;Outcome;Pathway interactions;Peripheral;Phenotype;Physiologic pulse;Play;precursor cell;preservation;Principal Investigator;Regulation;Research;research and development;Research Proposals;Role;Scientist;skill acquisition;skills;Source;Testing;therapeutic development;Tissues;tool;Training;transcriptome sequencing;validation studies;Volatile Fatty Acids

PROJECT_TITLE: Metabolite regulation of adipocyte differentiation in obesity


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Cancer;Colorectal Cancer;Digestive Diseases;Inflammatory Bowel Disease

PHR: Narrative Colorectal cancer (CRC) remains a leading cause of cancer-related death with limited treatment options. We recently identified a major protective role for microRNA, miR-146a, in limiting multiple angles of tumorigenic IL- 17-IL-17R signaling in CRC, and in this proposal, we use in vitro and in vivo experimental models in mice and CRC patient samples to probe the molecular mechanisms by which miR-146a mediates protection against CRC and assess targets for therapeutic intervention in a range of CRC models, including miR-146a mimic overexpression and miR-146a mimic in combination with chemotherapy. Elucidating the mechanisms by which miR-146a limits CRC may reveal novel targets for therapeutic intervention.

PI_NAMEs: GOPAL, MURUGAIYAN  (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: ApcMin/+ mice;Binding;Cancer Etiology;Cancer Model;Cessation of life;Chemoresistance;chemotherapy;Chronic;Clinical;Colitis;Colon;colon cancer patients;Colon Carcinoma;colon tumorigenesis;Colonic inflammation;Colorectal Cancer;colorectal cancer metastasis;Combination Drug Therapy;Crohn's disease;cytokine;Data;Development;Disease;Epithelial Cells;epithelial stem cell;Experimental Models;Genetic Polymorphism;Goals;Growth;gut inflammation;Human;IL17 gene;Immune response;Immunomodulators;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;innovation;interest;interleukin-23;Interleukins;Intervention;intestinal epithelium;Lesion;Link;Malignant - descriptor;Malignant Neoplasms;Mediating;metastatic colorectal;MicroRNAs;Modeling;Molecular Probes;Mus;Myeloid Cells;new therapeutic target;novel therapeutics;Outcome;overexpression;Pathway interactions;Patients;pre-clinical;Predisposition;premalignant;prevent;Production;Prognosis;Resistance;RIPK2 gene;Risk Factors;Role;Sampling;Signal Transduction;stem cells;System;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;Tissues;tool;TRAF6 gene;tumor;Tumor Promotion;tumorigenesis;tumorigenic;Ulcerative Colitis;Untranslated RNA

PROJECT_TITLE: MicroRNA control of tumor-promoting inflammation in colon cancer

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


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

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: PROJECT NARRATIVE Ongoing gene therapy (GT) clinical trials employing AAV vectors to treat adult patients with hemophilia A (HA) have established the promise of GT for correcting hereditary bleeding disorders in adults, yet there are many advantages to offering these therapies early in life. The proposed studies will test the safety and efficacy of current and novel GT approaches in the treatment of adult and pediatric patients. If the safety and advantage of this approach is unequivocally demonstrated, these patients could benefit from this important clinical option for treating genetic disorders.

PI_NAMEs: ALMEIDA-PORADA, GRACA DUARTE (contact);PORADA, CHRISTOPHER D

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: adeno-associated viral vector;Adrenal Cortex Hormones;Adult;Affect;Age;age related;Albumins;angiogenesis;animal data;Animal Model;Animals;Antibodies;antibody conjugate;Biology;Blood Coagulation Disorders;Blood Vessels;Capsid;Cell Cycle;cell type;Cells;Cellular Stress;Child;Childhood;Clinical;clinical risk;Clinical Trials;Clonal Expansion;Codon Nucleotides;curative treatments;cytokine;Data;delivery vehicle;DNA;Dose;drug metabolism;Early treatment;Ectopic Expression;endoplasmic reticulum stress;Endothelial Cells;Endothelium;Event;Exhibits;F8 gene;Fibrosis;Frequencies;gene therapy;gene therapy clinical trial;gene-targeted therapy;Genes;Genetic Diseases;Genome;genomic locus;Genomics;genotoxicity;Goals;Hemophilia A;Hemophilia B;Hepatic;Hepatocyte;Hepatotoxicity;Human;Immune;Immunity;improved;Incidence;Inflammation;Inflammatory Response;Inherited;Innate Immune Response;Life;Liver;liver cell proliferation;liver function;liver inflammation;liver preservation;Mediating;Natural Immunity;Neonatal;neonatal human;non-Native;novel;Participant;Patients;pediatric patients;Physiological;Play;Population;pre-clinical;prevent;Primary carcinoma of the liver cells;Production;Proliferating;prophylactic;Proteins;response;Risk;Safety;safety testing;Severities;Site;Specificity;System;Testing;Tissues;Toxic effect;Transaminases;transcriptomics;Transgenes;Urea;vasculogenesis;vector

PROJECT_TITLE: Using human liver tissue equivalents to optimize AAV-mediated GT and better define age-related clinical risks

STUDY_SECTION: GDD

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


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Diabetes;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention

ORG_CITY: TUCSON

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Research Statement Fetal growth restriction continues to contribute to major medical problems for the fetus, newborn, and even the adult, which is highlighted by their higher incidence of Type 2 Diabetes. At present, no effective therapies exist to correct metabolic morbidity cause by sub-optimal fetal nutrition. We plan to investigate new strategies to reduce fetal stress during placental insufficiency that promote normal β-cell development.

PI_NAMEs: LIMESAND, SEAN W (contact)

PROGRAM_OFFICER_NAME: HWA, ALBERT J

PROJECT_TERMS: Adult;Affect;Barker Hypothesis;Beta Cell;biological adaptation to stress;Cell Physiology;Cell Proliferation;cell type;Chronic;clinically relevant;comparison control;Cues;cytokine;Data;Defect;Depressed mood;Development;Diabetes Mellitus;diabetes risk;Disease;Disease Progression;DNA;effective therapy;endocrine pancreas development;Environment;Epigenetic Process;experimental study;Exposure to;extracellular;Failure;fetal;Fetal Growth Retardation;Fetal Reduction;Fetal Sheep;Fetus;fetus nutrition;Functional disorder;functional loss;Future;Genes;Glucose;Goals;Heterogeneity;Human;Hypoglycemia;Hypoxemia;Hypoxia;Impairment;improved;in utero;Incidence;Individual;Infant;Inflammatory;innovation;insight;Insulin;insulin secretion;islet;Islet Cell;Islets of Langerhans;Knowledge;late life;Longitudinal Studies;Maintenance;MALAT1 gene;Medical;Metabolic;Metabolic Diseases;Metabolism;Modeling;Modification;Morbidity - disease rate;neonate;Newborn Infant;NF-kappa B;Non-Insulin-Dependent Diabetes Mellitus;Norepinephrine;Nutrient;nutrient deprivation;offspring;Outcome;overexpression;Oxygen;Pathogenesis;Pathology;Pathology Report;Pathway interactions;Perinatal;perinatal health;Physiological;Placental Insufficiency;Predisposition;prenatal exposure;prenatal stress;preservation;prevent;Prevention;Process;Production;Regulation;Research;response;restoration;RNA Binding;Role;sheep model;side effect;stem;Stimulus;supplemental oxygen;Supplementation;Testing;Untranslated RNA;Work

PROJECT_TITLE: Prevention of Placental Insufficiency Improves Beta-Cells Function

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

ORG_STATE: CA

PHR: Project Narrative Allogeneic hematopoietic cell transplantation (Allo‐HCT) is a curative therapy for hematological malignancies, but graft versus host disease (GVHD), particularly corticosteroid resistant gut GVHD (SR‐Gut‐GVHD), remains the major obstacle, because the mortality of SR‐Gut‐GVHD is 70‐90%. The proposed studies will unravel the pathogenesis of SR‐Gut‐GVHD and develop new approaches for preventing and treating the disease.

PI_NAMEs: ZENG, DEFU  (contact)

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: Acetyl Coenzyme A;Acetylation;Adrenal Cortex Hormones;Affect;Allogenic;Anti-Inflammatory Agents;Apoptosis;ATP Citrate (pro-S)-Lyase;Bacterial Translocation;Biopsy Specimen;CD4 Positive T Lymphocytes;Cell Lineage;Cells;Colon;Compensation;curative treatments;cytokine;Cytometry;deoxyhypusine monooxygenase;deoxyhypusine synthase;Development;Disease;dysbiosis;Enzymes;EP300 gene;epigenetic regulation;Epithelial Cells;Equilibrium;FOXP3 gene;Functional disorder;Generations;Goals;graft vs host disease;Hematologic Neoplasms;Hematopoietic Stem Cell Transplantation;Histone Acetylation;histone acetyltransferase;Human;hypusine;IL18 gene;Immune response;Inflammation;Inflammatory;inhibitor;insight;interleukin-22;Interruption;intestinal epithelium;Intestines;Macrophage;Mediating;Metabolic;microorganism;Monoclonal Antibodies;Mononuclear;mortality;Motion;mouse model;Mus;novel;novel strategies;Ornithine Decarboxylase;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Phagocytes;Pharmaceutical Preparations;Play;Polyamines;prevent;Prevention;Putrescine;Regulatory T-Lymphocyte;Research Personnel;Resistance;response;restoration;Role;Specific qualifier value;Spermidine;Steroid Resistance;Steroids;T-Lymphocyte;Testing;Therapeutic;Tissues;transcytosis;transdifferentiation;translational approach

PROJECT_TITLE: Pathogenesis, prevention and treatment of corticosteroid-resistant gut GVHD

STUDY_SECTION: TTT

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


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: ROCHESTER

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: Poxviruses are an important global public health issue, with concerns for orthopoxviruses ranging from a clandestine release of smallpox to outbreaks of epizootic infections such as monkeypox. Understanding the biology of poxviruses is still a priority not only for preventing epidemics but also for the creation of next- generation poxvirus-based vaccines and oncolytic poxvirus platforms. This project will investigate the molecular mechanisms used by poxviruses to envelope new progeny virions, exit from the cell, and infect new hosts.

PI_NAMEs: WARD, BRIAN M (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Affect;Antibodies;Automobile Driving;Binding;Biological Warfare;Biology;cancer cell;Category A pathogen;Cell membrane;cell type;Cells;Complement;Complex;Cytoplasm;Data;design;Disease;Disease Outbreaks;DNA Viruses;Ensure;Epidemic;epizootic;Etiology;experimental study;extracellular;Family;Family member;Glycoprotein A33;Glycoproteins;Goals;GPA33 gene;Homologous Gene;Human;Infection;insight;Knowledge;Link;member;Membrane;Membrane Proteins;Molecular;Molluscum contagiosum virus;Monkeypox;Monkeypox virus;National Institute of Allergy and Infectious Disease;next generation;Oncolytic;Orthopoxvirus;Pathogenesis;Play;Poxviridae;poxvirus vectors;prevent epidemics;Process;Production;Proteins;Public Health;Publications;receptor;recombinant virus;Recombinants;Research;Role;Shapes;Site;Smallpox;Surface;System;Systemic infection;Testing;Tropism;tumor;United States National Institutes of Health;Vaccines;Vaccinia virus;Variola major virus;Viral;Viral Proteins;Virion;Virus;virus envelope;Work

PROJECT_TITLE: Understanding the Function of F13 as a Matrix Protein for Poxvirus Intracellular Envelopment

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Digestive Diseases;Genetics;Prevention;Substance Misuse

ORG_CITY: MADISON

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Excessive drinking and smoking promote the development of acute and chronic pancreatitis, two related inflammatory disorders of the pancreas lacking effective treatments. The mechanisms underlying alcohol and smoking toxicity to the pancreas are not fully understood, but recent evidence indicate that these factors alter the endoplasmic reticulum (ER), a cellular compartment needed to maintain pancreas function and the production of proteins to digest food. Using recently developed mouse models of pancreatitis, we plan to study how excessive drinking and smoking alters ER function resulting in disease onset and progression.

PI_NAMEs: GROBLEWSKI, GUY E (contact);LUGEA, AURELIA ;PANDOL, STEPHEN J.

PROGRAM_OFFICER_NAME: GAO, PETER

PROJECT_TERMS: Abdominal Pain;Acetyl Coenzyme A;Acetylation;Acetylesterase;Acinar Cell;Acute;acute pancreatitis;Alcohol abuse;Alcohol consumption;alcohol response;Alcoholic beverage heavy drinker;Alcoholic Pancreatitis;Alcohols;Animals;Attenuated;Automobile Driving;Binding Proteins;Biochemical;biological adaptation to stress;Carrier Proteins;Cell Death;Cell Fractionation;Cellular Stress;Cholelithiasis;Chronic;chronic alcohol ingestion;chronic pancreatitis;Cytoplasm;Data;Development;Diet;Disease;Disease Outcome;Disease Progression;disorder risk;drinking;Edema;effective therapy;Endoplasmic Reticulum;endoplasmic reticulum stress;Environmental Risk Factor;environmental stressor;Enzymes;Exhibits;Exocrine pancreas;Experimental Models;experimental study;Factor X;feeding;Fibrosis;Food;Functional disorder;Genes;Genetic;Genetic Transcription;Gland;Golgi Apparatus;Heavy Drinking;Hereditary Spastic Paraplegia;Heterozygote;Human;Immunologics;Immunoprecipitation;in vivo;Individual;Inflammation;Inflammatory;inhibitor;insight;Knockout Mice;life span;Link;Liquid substance;LoxP-flanked allele;Lysine;Mediating;Membrane;Membrane Proteins;Messenger RNA;misfolded protein;Modeling;Molecular;Molecular Chaperones;Molecular Target;Monitor;Morphology;mouse model;Mus;mutant;Mutation;Names;Neurodegenerative Disorders;Onset of illness;Oxidative Stress Induction;Pain;Pancreas;Pancreatic Diseases;Pancreatitis;Pathologic;Pathology;Pathway interactions;Peptide Initiation Factors;PERK kinase;Phosphorylation;polarized cell;Predisposition;prevent;problem drinker;Process;Production;programs;Protein Acetylation;protein degradation;protein expression;protein folding;protein transport;Proteins;Proteomics;Quality Control;Recovery;Recurrence;Regulation;response;Risk Factors;RNA Splicing;Role;secretory protein;sensor;Severities;Side;Signal Transduction;Smoking;Stress;stressor;System;Tamoxifen;Testing;Tobacco smoking behavior;Toxic effect;transcription factor;transcription factor CHOP;Transcriptional Regulation;Translations;Up-Regulation;Weight;Work

PROJECT_TITLE: Role of the ER acetyl CoA transporter in alcoholic pancreatitis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-A(90)]


ADMINISTERING_IC: EY

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Eye Disease and Disorders of Vision

ORG_CITY: COLLEGE STATION

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: TEXAS ENGINEERING EXPERIMENT STATION

PHR: PROJECT NARRATIVE Cataracts, a clouding of the natural lens, is treated by the surgical removal of the lens and implantation of an intraocular lens (IOL). The proposed work seeks to develop a superior IOL with a new material that will reduce post-surgical cell growth, eliminating the need for a 2nd surgery (laser capsulotomy) and improving vision outcomes.

PI_NAMEs: GRUNLAN, MELISSA  (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Adhesions;Adsorption;Adult;amphiphilicity;aqueous;Biological;biomaterial compatibility;Blindness;capsule;care costs;Cataract;Cataract Extraction;cell growth;Cell Line;Cells;Chemistry;Childhood;Clinical;Clinical Treatment;Complex;Complication;Data;design;diphenyl;Doctor of Medicine;Education;elastomeric;Elastomers;Epithelial Cells;Ethylene Oxide;Excision;Eye;flexibility;Formulation;Growth;Human;Hydrophobic Surfaces;implantation;improved;improved outcome;In Vitro;in vivo;Incidence;Income;innovation;Intraocular lens implant device;Intraocular Lens Implantation;Lasers;Length;lens;Lens development;manufacturing process;Mediating;Medical;medically underserved;medically underserved population;meetings;men;Methods;migration;Minority Groups;Modeling;Molds;Nature;Operative Surgical Procedures;Ophthalmologist;Oryctolagus cuniculus;Outcome;Pathologist;Patients;Phacoemulsification;Positioning Attribute;Predisposition;pressure;prevent;Production;Property;Proteins;Qualifying;Reactive Oxygen Species;Reporting;Research;Residual state;Resistance;Resources;Rest;Retinal Detachment;side effect;Silicones;Siloxanes;skills;standard care;Structure;success;Surface;Surgical incisions;Testing;Underrepresented Populations;Vision;Visual impairment;Woman;Work

PROJECT_TITLE: Improving Outcomes in Cataract Surgery: Intraocular Lenses (IOLs) Resistant to Cell Growth

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: WORCESTER

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: PROJECT NARRATIVE Despite current biologic and other therapeutic agents, inflammation-induced bone loss continues to be a significant clinical problem for patients with inflammatory arthritis. This grant will determine the potential of a novel inhibitor of bone formation, Schnurri-3 (SHN3), as a target to prevent or treat inflammatory arthritis-induced bone loss. Additionally, bone-specific recombinant adeno-associated virus carrying a SHN3 silencer will be tested for the treatment of systemic bone loss and/or healing of articular bone erosion in this setting.

PI_NAMEs: GRAVALLESE, ELLEN M;SHIM, JAE-HYUCK  (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: Ablation;Adaptor Signaling Protein;adeno-associated viral vector;Alleles;Anabolic Agents;ankle joint;antagonist;Antibodies;Arthritis;beta catenin;Binding;Binding Sites;Biochemical;Biological;bone;bone erosion;bone healing;bone loss;Bone Marrow;bone mass;Bone necrosis;bone repair;Bone Resorption;Cell Culture Techniques;Cell Lineage;Cell Separation;Cells;Clinical;cytokine;Data;Development;Disease;experimental study;Fracture;gene therapy;Genetic Transcription;Germ Lines;Grant;healing;Histologic;Histology;Human;IL17 gene;In Vitro;in vitro Model;in vivo;Inflammation;Inflammatory;Inflammatory Arthritis;inhibitor;innovation;Jaw;joint inflammation;Joints;Knee joint;Knock-in;Link;long bone;MAP Kinase Gene;Mass Spectrum Analysis;Mediating;Messenger RNA;microCT;Modeling;Molecular;mouse model;Mus;mutant;Mutation;New Agents;NF-kappa B;novel;novel strategies;novel therapeutics;osteoblast differentiation;Osteoblasts;Osteoclasts;Osteogenesis;Osteopenia;Osteoporosis;Osteoporosis prevention;overexpression;Pathway interactions;Patients;Pharmaceutical Preparations;Phase;Phosphorylation;prevent;Production;promoter;Proteins;Recombinant adeno-associated virus (rAAV);Resolution;response;Rheumatoid Arthritis;RNA Interference;Serum;side effect;Site;Sorting;spine bone structure;Stromal Cells;Synovitis;Testing;Therapeutic Agents;therapeutic target;Therapeutic Uses;TNF gene;Transcript;transcriptomic profiling;Up-Regulation;Validation;WNT Signaling Pathway;Work

PROJECT_TITLE: Novel approaches to promote healing of bone loss in inflammatory arthritis

STUDY_SECTION: SBSR

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


ED_INST_TYPE: PRIMATE CENTERS

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Conditions Affecting the Embryonic and Fetal Periods;Fetal Alcohol Spectrum Disorders (FASD);Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Substance Misuse

ORG_CITY: PORTLAND

ORG_DEPT: NEUROSCIENCES

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Therapeutic intervention for fetal alcohol spectrum disorder (FASD), a highly prevalent neurodevelopmental disorder in the United States, is most effective if initiated early. The research proposed here will use a nonhuman primate model of FASD to develop in utero and neonatal MRI methods for detecting brain abnormalities and predict the severity of behavioral impairments associated with fetal exposure to alcohol. Studies of neural activity in the brains of ethanol-exposed animals will provide an understanding of the neurocircuitry involved in behavioral impairments associated with FASD, and guide the interpretation of fetal and neonatal MRI findings.

PI_NAMEs: CUZON CARLSON, VERGINIA CARMELLA (contact);KROENKE, CHRISTOPHER D;SULLIVAN, ELINOR L.

PROGRAM_OFFICER_NAME: EGLI, MARK

PROJECT_TERMS: Achievement;adverse outcome;Affect;Age;Age Months;Alcohol consumption;alcohol exposure;Alcohols;Anatomy;Animal Model;Animals;Awareness;Axon;Behavior;Behavior assessment;behavior measurement;Behavioral;behavioral impairment;binge drinking;Brain;brain abnormalities;Brain region;Cells;Cerebellum;Child;clinically relevant;cognitive development;cognitive function;comparison control;Control Animal;Data;data reduction;detection method;Development;Developmental Process;drinking;Early Diagnosis;early drinking;economic cost;efficacious treatment;Electrophysiology (science);emotion regulation;Equilibrium;Ethanol;Exhibits;experimental study;Exposure to;fetal;Fetal alcohol effects;Fetal Alcohol Exposure;Fetal Alcohol Spectrum Disorder;Fetus;Fiber;First Pregnancy Trimester;Functional impairment;Functional Magnetic Resonance Imaging;Gestational Age;Glutamates;Grant;Growth;Histology;Human;image reconstruction;Immunohistochemistry;Impaired cognition;Impairment;improved;in utero;Incidence;Individual;Infant;Intervention;Investments;Lead;life span;Macaca mulatta;Magnetic Resonance Imaging;Measurement;Measures;Methods;Modality;Modeling;Monkeys;Motion;Motor;motor behavior;motor impairment;neonatal magnetic resonance imaging;Nervous System Trauma;neural;neural circuit;Neuroanatomy;Neurodevelopmental Disorder;neuroimaging;Neurologic Deficit;Neurons;nonhuman primate;novel;offspring;older women;Oral;Outcome;patch clamp;postnatal;postsynaptic;Pregnancy;prenatal exposure;Prevalence;Prevention;Procedures;Process;putamen;Quality of life;Research;Rhesus;Risk Reduction;School-Age Population;Self Administration;Severities;Slice;socioeconomics;Somatosensory Cortex;Structure;Synapses;System;Techniques;Testing;Therapeutic Intervention;Three-Dimensional Image;transmission process;United States;Validation;white matter;Work

PROJECT_TITLE: Functional consequences of fetal-alcohol-induced brain growth abnormalities identified with in utero MRI

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Biotechnology;HIV/AIDS;Immunization

ORG_CITY: Juno Beach

ORG_NAME: EMMUNE, INC

ORG_STATE: FL

PHR: PROJECT NARRATIVE  The HIV field is moving towards the use of long-acting injectable drugs. This project will extend the longevity of eCD4-Ig in the body by engineering which sugar molecules that are attached to it. The same approach can be used to extend the longevity of other therapeutics for treating and preventing HIV infection.

PI_NAMEs: ALPERT, MICHAEL DAVID (contact);HUANG, MIA L

PROGRAM_OFFICER_NAME: LACOURCIERE, GERARD

PROJECT_TERMS: adeno-associated viral vector;Antibodies;antibody mimetics;antibody-dependent cell cytotoxicity;Area;Asialoglycoprotein Receptor;Binding;carbohydrate structure;Carbohydrates;Cell Line;Chinese Hamster Ovary Cell;Circulation;Cyclic GMP;Data;dimer;DNA cassette;Dose;Drug Kinetics;Engineering;Enzymes;FCGR3B gene;Fucose;Galactose;Glucosamine;Glycoengineering;glycosylation;Goals;Half-Life;head-to-head comparison;HIV;HIV Infections;HIV Receptors;Human;improved;Infection;inhibiting antibody;Injectable;knock-down;Link;Longevity;Macaca mulatta;Mannose;manufacture;Mediating;mouse model;Muscle;National Institute of Allergy and Infectious Disease;neonatal Fc receptor;neutralizing antibody;overexpression;peptidomimetics;Pharmaceutical Preparations;Plasma;Polysaccharides;prevent;Primates;Property;Proteins;receptor;receptor binding;Recombinant Proteins;Sialic Acids;sialylation;SIV;small hairpin RNA;stable cell line;sugar;Testing;Therapeutic;Therapeutic antibodies;therapeutic protein;Time;Transgenic Mice;Treatment Efficacy;Viral Load result;viral resistance;Work

PROJECT_TITLE: Glycoengineering eCD4-Ig


NIH_SPENDING_CATS: Autoimmune Disease;Data Science;Genetics;Infectious Diseases

ORG_CITY: WASHINGTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: PROJECT NARRATIVE The human immune system plays a vital role in our ability to fight infection; however, it can also cause harm in the form of autoimmune diseases, such as Type 1 diabetes, lupus, and multiple sclerosis. A wealth of information relevant to immunological research has been captured in biomedical databases, but this information can be hard to use because it is scattered and recorded in incompatible formats. This project will address this barrier by connecting the Immune Epitope Database (IEDB), a resource that compiles key information about the immune system, to other major resources (e.g., UniProtKB) to assist researchers and clinicians in their efforts to understand healthy and abnormal immune responses.

PI_NAMEs: NATALE, DARREN A (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Address;Affect;Allergic Disease;Amino Acid Sequence;Animals;Antibodies;Antigens;Area;Autoimmune Diseases;Autoimmunity;Awareness;Base Sequence;Catalogs;Clinical;Communicable Diseases;Communities;community building;community engagement;Consumption;Cross Reactions;cross reactivity;Data;data exchange;data visualization;Databases;Dedications;Detection;Disease;disease model;Distance Learning;druggable target;Educational workshop;Ensure;Environment;Epitopes;fighting;Funding;Generations;genetic variant;Genetic Variation;Goals;Growth;Homologous Gene;Homologous Protein;Human;human disease;Human Genetics;Hypersensitivity;Immune;Immune Evasion;Immune response;Immune system;Immunologics;Immunology;improved;Infection;information display;insight;Insulin-Dependent Diabetes Mellitus;interest;Knowledge;Knowledge Discovery;knowledge graph;Link;Lupus;Maps;meetings;model organism;Monitor;Multiple Sclerosis;National Institute of Allergy and Infectious Disease;nonhuman primate;novel;Ontology;Organism;Orthologous Gene;outreach;pathogen;Pharmaceutical Preparations;Play;Post-Translational Protein Processing;prevent;protein protein interaction;Proteins;Publications;Research;Research Personnel;Resource Informatics;Resources;Role;Sampling;Semantics;Sequence Homologs;Site;social media;T-Cell Receptor;T-Lymphocyte Epitopes;tool;translational scientist;Transplantation;usability;Variant;Visualization;Visualization software;web site;Work

PROJECT_TITLE: Semantic integration of protein epitopes and functional features for infectious and autoimmune disease knowledge discovery


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Genetics;Human Genome;Mental Health;Mental Illness;Neurosciences;Social Determinants of Health

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE Psychological stress increases the susceptibility to neuropsychiatric disorders, such as anxiety, depression, and memory loss. Using interdisciplinary methods, we will uncover molecular, cellular and circuitry mechanisms underpinning a non-conventional role of the cerebellum in mediating stress responses. The novel insights will help develop therapeutic strategies for mental illness.

PI_NAMEs: YANG, YI-MEI (AMY)  (contact)

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Action Potentials;Address;adeno-associated viral vector;Adverse event;Affect;Animals;Anxiety;Anxiety Disorders;Area;Axon;Back;Behavioral;behavioral phenotyping;biological adaptation to stress;Brain;Brain region;Cell membrane;Cell Separation;cell type;Cerebellar Cortex;Cerebellar Diseases;Cerebellar Nuclei;Cerebellum;Childhood;chromatin immunoprecipitation;cohort;Corticosterone;Cre lox recombination system;Data;Dependovirus;designer receptors exclusively activated by designer drugs;Dimensions;Disease;early life stress;Electrophysiology (science);Epigenetic Process;Feedback;Fluorescence-Activated Cell Sorting;Frequencies;Gene Expression;Gene Expression Profile;gene network;Gene Transfer;Genes;genome-wide;Genomics;Glucocorticoid Receptor;Histone Acetylation;Hormones;Impaired cognition;Impairment;improved;insight;interdisciplinary approach;Ion Channel;knock-down;Knock-out;Knowledge;Life;maladaptive behavior;Mediating;Mediator;Membrane;Memory Loss;Mental Depression;Mental disorders;Mental Health;Messenger RNA;Methods;Molecular;Morphology;Motor;Mus;Neocortex;Neonatal;neural circuit;Neurobiology;Neurons;neuropsychiatric disorder;new therapeutic target;novel;novel therapeutic intervention;Output;overexpression;patch clamp;patch sequencing;Pathway interactions;Positioning Attribute;Potassium Channel;Predisposition;Process;promoter;prospective;psychiatric symptom;Psychological Stress;psychological stressor;Psychopathology;Purkinje Cells;Reporting;response;Rodent;Role;single-cell RNA sequencing;Slice;social;Social Change;Social isolation;spatiotemporal;Specific qualifier value;Stimulus;Stress;stressor;Structure;Synapses;System;Techniques;Testing;Thalamic structure;Therapeutic;Transcriptional Regulation;transcriptome sequencing;transcriptomic profiling;Up-Regulation;Ventral Lateral Thalamic Nucleus;Ventral Tegmental Area;Vestibular nucleus structure;Viral Genes;Weaning;Work

PROJECT_TITLE: Neurobiology of stress in the cerebellar circuitry


ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Biotechnology;Genetics;Machine Learning and Artificial Intelligence

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: WORCESTER POLYTECHNIC INSTITUTE

PHR: The goal of this proposal is to investigate a link between the alternatively spliced isoforms and their proteomic stability, ability to rewire protein-protein interaction, and the overall functional impact in the context of different phenotypes. We propose to develop a symbiotic data-driven approach where the high-throughput wet-lab experiments are designed not only to validate the machine learning predictors but will be used to inform them through a computation-experiment discovery cycle.

PI_NAMEs: KORKIN, DMITRY  (contact);SHEYNKMAN, GLORIA

PROGRAM_OFFICER_NAME: DENNIS, ALLISON FRANCES

PROJECT_TERMS: Activities of Daily Living;Alternative Splicing;Benchmarking;Binding;Bioinformatics;Biological Assay;Biology;Cancer cell line;Case Study;Cell Physiology;Cells;Computing Methodologies;Consumption;Data;Data Set;detection method;Development;Disease;disease phenotype;Evaluation;Exhibits;Experimental Designs;experimental study;gene function;Genes;Genetic;Genome;Genomics;Goals;high throughput screening;Human;human disease;Human Genome;human tissue;improved;in silico;In Vitro;in vivo;laboratory experiment;Life Cycle Stages;Link;Literature;machine learning algorithm;machine learning method;machine learning prediction;Maps;Mass Spectrum Analysis;Mathematics;Measures;Methodology;Methods;Molecular;mRNA Precursor;novel;Pathway interactions;Pattern;Peptides;Phenotype;Physiological;Property;protein function;Protein Isoforms;protein protein interaction;Protein-Protein Interaction Map;Proteins;proteogenomics;Proteome;Proteomics;Resolution;Role;stem cells;Structure;Technology;Time;tool;transcriptome sequencing;transcriptomics;Translating;Translations;Validation;Variant;Work

PROJECT_TITLE: Predicting the functional impact of alternative splicing on protein-protein interactions using an integrated approach

STUDY_SECTION: BLR

STUDY_SECTION_NAME: Biomedical Informatics, Library and Data Sciences Review Committee[BLR]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Diabetes

ORG_CITY: COLUMBIA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

ORG_STATE: MO

PHR: PROJECT NARRATIVE The prevalence of type 2 diabetes (T2D) is increasing by alarming proportions in the US and worldwide. Over the last two decades, the number of new cases of diabetes has almost tripled in the US and current projections estimate that one in three Americans will have diabetes by 2050. This has a tremendous health care significance, as eight out of 10 patients with T2D die from cardiovascular disease. Vascular insulin resistance is an important factor in the pathogenesis of T2D and cardiovascular disease. The proposed study will determine the role that ADAM17 activity has in mediating microvascular insulin resistance in T2D with the goal of elucidating new therapeutic strategies.

PI_NAMEs: MARTINEZ-LEMUS, LUIS A (contact);PADILLA, JAUME

PROGRAM_OFFICER_NAME: REID, DIANE M

PROJECT_TERMS: Abdomen;American;Animal Model;Arteries;Biopsy;Blood flow;blood glucose regulation;Blood Vessels;Cardiovascular Diseases;Cardiovascular system;Cell membrane;Cell surface;Clinical Trials;Data;Defect;Diabetes Mellitus;Double-Blind Method;Down-Regulation;efficacy evaluation;Endothelial Cells;Endothelium;Enzymes;Exhibits;experimental study;extracellular;gain of function;genetic manipulation;Glucose Clamp;glucose uptake;glycemic control;Goals;Harvest;Healthcare;Human;Hyperinsulinism;Impairment;improved;inhibitor;innovation;Insulin;Insulin Receptor;Insulin Resistance;insulin sensitivity;insulin signaling;Insulin Signaling Pathway;Integral Membrane Protein;Intervention;Leg;loss of function;Matrix Metalloproteinases;Mediating;Metabolic Diseases;Methodology;Nitric Oxide;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutic intervention;Operative Surgical Procedures;Oral Administration;overexpression;Pathogenesis;Patients;Phosphatidylserines;Precipitating Factors;preservation;Prevalence;prevent;Production;Protein Kinase C;Publishing;Randomized;receptor;Research;Resistance;response;Role;Skeletal Muscle;Surface;Testing;Therapeutic;therapeutic development;Tissues;Treatment Efficacy;vascular bed;Vascular Endothelium;Vasodilation;Vasodilator Agents;Work

PROJECT_TITLE: Targeting ADAM17 activity for correction of vascular insulin resistance in type 2 diabetes

STUDY_SECTION: CICS

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Congenital Structural Anomalies;Epilepsy;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Prevention;Rare Diseases

ORG_CITY: DETROIT

ORG_DEPT: PEDIATRICS

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: PROJECT NARRATIVE In this renewal application we will test a novel, rapid, non-sedate, non-contrast MRI approach to detect brain vascular and parenchymal abnormalities with a short, few-minute acquisition time in children with Sturge- Weber syndrome (SWS); this new approach can be also readily applied in other pediatric brain disorders. We will also study the effects of venous vascular remodeling and structural brain reorganization on neurocognitive outcome of school-age and adolescent children and young adults with SWS, who could benefit from targeted interventions to optimize clinical outcome. Finally, we will use brain tissue from SWS epilepsy surgeries to identify vascular and non-vascular cell types harboring the SWS-associated GNAQ somatic gene mutation and evaluate how the mutation is associated with brain abnormalities and protein changes related to abnormal cell development that could be targeted by pharmacological treatments.

PI_NAMEs: JUHASZ, CSABA  (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Abnormal Cell;Adolescent;Adolescent and Young Adult;Affect;Age;angiogenesis;anti-epileptic agents;Aspirin;Blood Vessels;Brain;brain abnormalities;brain cell;Brain Diseases;Brain Injuries;Brain Pathology;brain surgery;brain tissue;Brain Vascular Malformation;cell type;Cells;Cerebral hemisphere;cerebrovascular;Child;Childhood;Clinical;clinical imaging;clinical practice;Cognitive;cognitive function;connectome;Contralateral;cost;Crowding;Data;deep vein;design;Detection;Development;Diffusion Magnetic Resonance Imaging;Disease;Early Diagnosis;Early Intervention;early screening;Epilepsy;Executive Dysfunction;executive function;Face;follow-up;FRAP1 gene;Frequencies;Functional disorder;Gene Mutation;GNAQ gene;Harvest;high risk;Histopathology;Image;imaging approach;Impaired cognition;improved;Injections;innovation;Intervention;Ipsilateral;Language;laser capture microdissection;Left;Leptomeninges;Lesion;Life;Magnetic Resonance Imaging;malformation;Modeling;molecular marker;molecular targeted therapies;Monitor;Motor;motor symptom;Mutation;Nervous System Disorder;Neurocognitive;Neurocutaneous Syndromes;neuroimaging;Neurologic Symptoms;Neurons;non-verbal;novel;novel diagnostics;novel strategies;Operative Surgical Procedures;Outcome;Pathology;Patient Recruitments;Patients;Pharmaceutical Preparations;Pharmacological Treatment;Phenotype;Port-Wine Stain;postnatal;Predisposition;preservation;prevent;Preventive;Process;programs;Proteins;Protocols documentation;Rapid screening;Research;Risk;Role;School-Age Population;screening;Sedation procedure;Seizures;Shapes;Signal Pathway;Somatic Mutation;Specimen;Sturge-Weber Syndrome;Subgroup;Techniques;Testing;Therapeutic;Therapeutic Trials;Time;Tissues;tool;treatment effect;United States National Institutes of Health;Vascular Endothelial Growth Factors;Vascular remodeling;Venous;Venous Malformation;verbal;young adult

PROJECT_TITLE: Longitudinal neuroimaging in Sturge-Weber syndrome


NIH_SPENDING_CATS: Clinical Research;Disability Research;Hematology;Infectious Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Sepsis

PHR: PROJECT NARRATIVE The research program outlined in this proposal is relevant to public health because it will utilize detailed electronic health record, clinical trial, and biomarker data combined with machine learning to improve the identification, risk stratification, and discover important subphenotypes of sepsis to improve patient outcomes. This work will result in novel algorithms that can be implemented to deliver early, personalized care to decrease preventable morbidity and mortality from sepsis. Therefore, the proposed research is relevant to the part of the NIH’s mission that pertains to enhancing health, lengthening life, and reducing illness and disability.

PI_NAMEs: CHURPEK, MATTHEW MICHAEL (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Address;Age;Algorithms;Award;Biological Markers;Biology;Caring;Cessation of life;Characteristics;Clinical;Clinical Trials;Collection;Complex;cost;Critical Illness;Data;deep learning;Department of Defense;disability;Early identification;Electronic Health Record;Functional disorder;Funding;Future;Goals;Health;Health Care Costs;high risk;Hospitalization;Hospitals;Immune response;Impaired cognition;improved;Infection;Infectious Agent;innovation;International;Knowledge;Life;Lighting;Machine Learning;machine learning method;member;Mission;Modeling;Morbidity - disease rate;mortality;National Institute of General Medical Sciences;Natural Language Processing;neglect;novel;Organ;Patient Care;patient stratification;Patient-Focused Outcomes;Patients;Peer Review;personalized care;personalized medicine;Phenotype;physically handicapped;Population;preventable death;programs;Public Health;Publications;Publishing;Research;risk stratification;Secure;Sepsis;Societies;Structure;Study Section;success;Survivors;Syndrome;Time;tool;treatment strategy;United States;United States National Institutes of Health;Vision;ward;Work

PROJECT_TITLE: Sepsis Early Prediction and Subphenotype Illumination Study (SEPSIS)

STUDY_SECTION: MRAC

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


NIH_SPENDING_CATS: Aging;Immunotherapy;Osteoporosis

ORG_DEPT: PATHOLOGY

PHR: Project Narrative  We have identified a new subset of macrophages, which express TGFβ1 on their cell surfaces and are present in high numbers in the bone marrow of aged mice where they appear to inhibit bone formation and interact with T lymphocytes to cause low level chronic inflammation during aging. We plan to further investigate the molecular mechanisms whereby interactions between these macrophages and T lymphocytes cause bone loss and low level chronic inflammation in aging mice and to determine if our recently patented bone-targeted hydroxychloroquine can block these interactions to prevent and reverse age-related osteoporosis.

PI_NAMEs: YAO, ZHENQIANG  (contact)

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: Adaptor Signaling Protein;Age;Age-Related Bone Loss;Age-Related Osteoporosis;Aging;Attenuated;Autoimmune Diseases;Binding;Biological;bisphosphonate;bone;bone cell;Bone Formation Inhibition;Bone Formation Stimulation;bone loss;Bone Marrow;Bone Resorption;Bone Resorption Inhibition;bone turnover;CD4 Positive T Lymphocytes;Cell Aging;Cell Communication;Cell Physiology;Cell surface;Cells;Chemicals;chemokine;Chronic;Coupled;CXCR3 gene;cytokine;Enterobacteria phage P1 Cre recombinase;FDA approved;Helper-Inducer T-Lymphocyte;Homeostasis;Hydroxychloroquine;IFNGR1 gene;Immune;immune checkpoint;In Vitro;Inflammaging;Inflammation;Inflammatory;inhibitor;Integrin beta Chains;Interferon Type II;Interleukin-12;Interleukin-2;ITGAM gene;Knock-out;Legal patent;Link;Macrophage;Maps;Mediating;Membrane;Mesenchymal Stem Cells;Modeling;Molecular;Mus;novel;novel strategies;old mice;osteoblast differentiation;Osteoblasts;Osteoclasts;Osteogenesis;osteoimmunology;Osteoporosis;Osteoporotic;Play;prevent;Production;programmed cell death protein 1;promoter;Proteins;receptor;Reporting;Role;senescence;Surface;T-Cell Activation;T-Lymphocyte;Testing;Th1 Cells;TNF receptor-associated factor 3;TNFSF11 gene;transcriptomics;Transforming Growth Factor beta

PROJECT_TITLE: Role of Macrophage in Osteoimmunology with Aging


NIH_SPENDING_CATS: Pain Research

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE This application proposes to advance single particle cryo-EM technology so that challenging biological questions beyond atomic structure determinations, particularly protein dynamics and conformational transitions between conformational states, can be studied.

PI_NAMEs: CHENG, YIFAN  (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Address;Biochemical;Biological;Biological Models;Biophysics;Complex;conformational conversion;Cryoelectron Microscopy;Ion Channel;macromolecule;Methods;Molecular Conformation;Nociceptors;novel;particle;pharmacologic;Physiological;Protein Conformation;Protein Dynamics;Sampling;Signal Transduction;Stimulus;structural biology;Structure;Technology;tool;TRP channel;TRPV1 gene

PROJECT_TITLE: Advancing cryo-EM technology to address difficult biological questions

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Clinical Research;Genetics;Hematology;Pediatric;Primary Immunodeficiencies;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE The goal of this application is to provide additional training for Sharon Singh MD, a Pediatric Hematologist/Oncologist, in the evaluation of hematopoiesis by investigating how ribosomal protein haploinsufficiency alters stem and progenitor cell function. The applicant will be guided by a team of senior mentors with expertise in stem cell biology, erythropoiesis and anemia with the goal of understanding how defects in protein synthesis affect red cell biology. There is a critical need for further work in this field, which has implications for a wide variety of disorders that lead to anemia in children; execution of the proposed aims will mature the development of a pediatric clinician-scientist with expertise in the evaluation of normal and abnormal hematopoiesis.

PI_NAMEs: SINGH, SHARON A (contact)

PROGRAM_OFFICER_NAME: HATTANGADI, SHILPA MANOHAR

PROJECT_TERMS: Affect;Age;Age Months;Anemia;Animal Model;Aplastic Anemia;Basic Science;Biological Assay;Birth;Blood Transfusion;Bone Marrow;bone marrow failure syndrome;burden of illness;career;Cell Count;Cell Culture Techniques;Cell Cycle;Cell Cycle Regulation;Cells;Cellular biology;Cellular Stress;CFU-E;Characteristics;Child;Childhood;Chronic;Clinical;Collaborations;Complex;critical developmental period;critical period;Data;Defect;design;Development;Diamond-Blackfan anemia;Disease;Disease remission;Dysmyelopoietic Syndromes;Education;Embryo;Environment;Erythrocytes;erythroid differentiation;Erythropoiesis;Etiology;Evaluation;exhaustion;experimental study;Failure;Functional disorder;Funding;GATA1 gene;Gene Proteins;Genetic;Genetic Transcription;Germ-Line Mutation;Goals;Health;Hematopoiesis;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Heme;Hemoglobin;Heterozygote;Human;Hydrops Fetalis;immune activation;improved;in utero;In Vitro;in vivo;Inbred Mouse;Individual;Inherited bone marrow failure;Innate Immune System;Junior Physician;Laboratory Research;life span;Macrocytic Anemia;Mediator;Mentors;Mentorship;Michigan;Modeling;mortality;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;Neonatal;Newborn Infant;Normal Cell;novel;novel therapeutics;Pathogenesis;Pathway interactions;patient registry;Patients;Pediatric Hematologist;Pediatric Hematology;Pediatric Oncologist;Penetrance;Persons;Phenotype;Physicians;Play;prevent;Pronormoblasts;Protein Biosynthesis;Protein Deficiency;Proteins;Reactive Oxygen Species;Research;Resolution;Resources;Ribosomal Proteins;Ribosomes;Role;Scientist;Severities;Spontaneous Remission;stem cell biology;stem cell function;stem cells;Stress;Testing;Toxic effect;Training;Transfusion;Translations;Transplantation;Universities;Work

PROJECT_TITLE: The role of Rpl5 haploinsufficiency in hematopoietic stem/progenitor cell function in Diamond Blackfan anemia

STUDY_SECTION: DDK

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Eating Disorders;Mental Health;Neurosciences;Nutrition;Obesity;Prevention

ORG_CITY: CHAMPAIGN

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: Project Narrative: Obesity and the associated metabolic syndrome present an enormous public health burden. Although behavioral (dieting and exercise), pharmacological, and surgical approaches exist for weight loss, many individuals who lose weight are unable to sustain this weight loss due to compensatory behavioral and neuroendocrine pathways promoting rebound weight gain. This proposal aims to characterize the utility of MC3R inhibition as a novel therapeutic approach for obesity, primarily via the ability of MC3R antagonism to prevent weight regain.

PI_NAMEs: SWEENEY, PATRICK  (contact)

PROGRAM_OFFICER_NAME: CUMMINGS, DIANA M

PROJECT_TERMS: American;Anorexia;antagonist;Behavior;Behavioral;Binding;Biology;Body Weight;Body Weight decreased;Brain;Brain imaging;Calcium;Caloric Restriction;Cone;Data;Diet;diet and exercise;dietary restriction;dieting;druggable target;Eating;Eating Disorders;efficacy testing;Electrophysiology (science);Evaluation;Exercise;experience;experimental study;Fasting;feeding;Feeding behaviors;gamma-Aminobutyric Acid;Genetic;Grant;Hunger;Hypothalamic structure;Image;Impairment;In Situ Hybridization;in vivo;Individual;Kinetics;knock-down;Knockout Mice;liraglutide;Maps;Mediating;Melanocortin 3 Receptor;Melanocortin 4 Receptor;Mentors;Mentorship;Metabolic;Metabolic syndrome;microendoscopy;Modality;Molecular;mouse model;Mus;neural circuit;Neuroendocrinology;Neurons;neuroregulation;Neurosciences;Neurosecretory Systems;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Obesity;obesity treatment;Operative Surgical Procedures;Pathway interactions;Patients;Peptides;pharmacologic;Pharmacology;Physiology;presynaptic;prevent;programs;Public Health;Publishing;Reporting;Research;Research Personnel;response;Role;Site;Slice;Structure of nucleus infundibularis hypothalami;Testing;Therapeutic;therapeutic target;Training;United States;Viral;Weight;Weight Gain;weight maintenance;Weight-Loss Drugs

PROJECT_TITLE: MC3R inhibition as a strategy to maintain weight loss in obesity

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


NIH_SPENDING_CATS: Diabetes;Nutrition;Obesity;Prevention

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Narrative This project will study the molecular mechanisms by which insulin stimulates glucose uptake in muscle and fat cells, and how these mechanisms are affected in insulin resistant states such as type 2 diabetes. Improved understanding of these mechanisms may lead to new approaches to prevent or treat diabetes and obesity.

PI_NAMEs: BOGAN, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Address;Adipocytes;Affect;Aminopeptidase;Attenuated;attenuation;Binding;blood glucose regulation;C-terminal;Cardiovascular Diseases;Cell membrane;Cell surface;Cells;Complex;Data;Development;Diabetes Mellitus;Diet;Disease;Dyslipidemias;Energy Metabolism;Equilibrium;Exercise;Fasting;Fatty acid glycerol esters;fatty acid oxidation;fatty acylation;Functional disorder;Gene Expression;Genetic Transcription;glucose metabolism;Glucose Transporter;glucose uptake;GLUT 4 protein;Goals;Golgi Apparatus;High Fat Diet;Homeostasis;Hormones;Hypertension;Impairment;improved;in vivo;Individual;Insulin;Insulin Resistance;insulin signaling;Intracellular Membranes;Link;lipid metabolism;Lipoprotein Receptor;Mediating;Membrane;Metabolic Diseases;Metabolic syndrome;Modeling;Molecular;Mus;Muscle;Muscle Cells;N-terminal;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;Obesity;Pathogenesis;Pathway interactions;Peptide Hydrolases;Peptides;Physiological;PIK3CG gene;prevent;Prevention;Process;Proteins;Regulation;Role;Signal Pathway;Signal Transduction;Site;Skeletal Muscle;sortilin;Stroke;syntaxin;syntaxin A;Testing;Thermogenesis;trafficking;Vasopressins;Vesicle;Work

PROJECT_TITLE: Vesicle Translocation and the Metabolic Syndrome

STUDY_SECTION: POMD

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


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

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: The current understanding of Alzheimer’s disease (AD) beyond amyloid β (Aβ) depositions and tau tangles remains incomplete. Our proposed study will address the role of astrocytes, the most abundant cell type in the brain, in regulating AD pathogenesis and progression. Successful accomplishment of our study will pave the way for future development of novel therapeutic strategies to diminish the detrimental astrocyte response in AD.

PI_NAMEs: QIN, HONGWEI ;WANG, QIN  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: abeta deposition;Address;Affect;Age;age related;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease therapy;Amyloid beta-Protein;Animal Disease Models;Astrocytes;Attenuated;Automobile Driving;Autopsy;beta amyloid pathology;Biology;Brain;brain cell;cell type;Cells;Cognition;Cognitive deficits;cognitive performance;Complex;cytokine;Data;Development;Disease;Disease Progression;experience;Family;Functional impairment;Future;Genes;glial activation;Goals;Heterogeneity;Human;improved;Inflammatory;inflammatory marker;inhibitor;insight;Interferons;Interleukin-6;Knock-in;Knock-in Mouse;Knowledge;Mediating;member;Microglia;Modeling;Molecular;mouse model;Mus;Nerve Degeneration;Neurofibrillary Tangles;neuroinflammation;Neurons;neuropathology;neurophysiology;neutralizing antibody;novel;novel therapeutic intervention;oncostatin M;OSMR gene;Pathogenesis;Pathologic;Pathology;Pathway interactions;Phagocytosis;pharmacologic;Play;Population;pre-clinical;Process;Property;receptor;Regulation;Resolution;response;Role;Senile Plaques;Senility;Signal Transduction;Spatial Distribution;tau Proteins;Testing;Therapeutic;transcriptomics

PROJECT_TITLE: Astrocytic OSMR/JAK/STAT signaling in AD

STUDY_SECTION: CMBG

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


NIH_SPENDING_CATS: Aging;Contraception/Reproduction;Estrogen;Eye Disease and Disorders of Vision;Genetics;Menopause;Neurodegenerative;Neurosciences;Women's Health Research

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Project Narratives The goal of this proposal is to determine the role of estrogen and its receptors (estrogen receptor 1 and G protein coupled estrogen receptor 1) in regulating eye pressure by affecting the different parts in the anterior chamber of the eye. Eye pressure is the primary and only treatable risk factor with glaucoma patients in the clinic. The successful completion of this project will help uncover critical information on the specific roles of estrogen and its signaling pathways in regulating eye pressure and identify new treatment targets to lower eye pressure more effectively in glaucoma patients.

PI_NAMEs: LIU, YUTAO  (contact)

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: 4-vinylcyclohexene diepoxide;Affect;Age;Age at Menarche;Agonist;antagonist G;Anterior;anterior chamber;aqueous;Aqueous Humor;Aromatase;Bioinformatics;Cattle;Cell Physiology;Cells;Chemicals;Clinic;Clinical;contrast imaging;Cornea;Data;Disease;Endothelial Cells;ERR1 protein;ESR1 gene;Estradiol;Estrogen decline;Estrogen Receptors;Estrogens;Extracellular Matrix;Eye;eye chamber;Eyedrops;Family suidae;Female;Fertility;follow-up;gene network;Genes;genetic association;genome wide association study;genomic locus;Glaucoma;Goals;GPER gene;Heterozygote;Histology;Hormone replacement therapy;Hormone use;Human;human old age (65+);In Vitro;in vivo;Individual;inhibitor;Injections;innovation;Knockout Mice;Magnetic Resonance Imaging;Mechanics;Mediating;Menarche;Menopause;Modeling;modifiable risk;Monitor;mouse model;Mus;Nerve Degeneration;Nerve Fibers;new therapeutic target;NG-Nitroarginine Methyl Ester;Nitric Oxide;NOS3 gene;novel;Ocular Hypertension;Oral Contraceptives;Ovariectomy;Pathogenesis;Pathway interactions;Patients;Periodicity;Physiologic Intraocular Pressure;Physiological;Postmenopause;Pregnancy;pressure;Primary Cell Cultures;Primary Open Angle Glaucoma;Production;protective effect;Proteins;Rattus;receptor;Receptor Signaling;Regulation;Research;Resistance;response;Retina;Retinal Degeneration;Risk;Risk Factors;Role;sex;Signal Pathway;Signal Transduction;single nucleus RNA-sequencing;Stains;stem;Steroids;Stretching;Structure of sinus venosus of sclera;System;Testing;therapeutic target;Thick;Tissues;Trabecular meshwork structure;Transforming Growth Factor beta;Variant;Vision;Visual Fields;Woman

PROJECT_TITLE: Estrogen and its Receptor in Intraocular Pressure Regulation

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


NIH_SPENDING_CATS: Aging;Genetics;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative Remarkably, the changes in microtubule and actin networks as a function of aging have not been thoroughly characterized. Our studies will address fundamental questions related to the role of the nuclear-cytoskeletal linker protein, SUN1, and tubulin modifications in nuclear shape changes and in physiological and pathological models of aging, and we will determine whether these alterations are a cause or consequence of aging. Our studies will also provide insights into the changes in chromatin topology sustained by cells that age through normal or pathological mechanisms.

PI_NAMEs: DYNLACHT, BRIAN D (contact)

PROGRAM_OFFICER_NAME: OROSZ, ANDRAS

PROJECT_TERMS: Ablation;Actins;Aging;aging mechanism;aging process;alpha Tubulin;Biochemical;Biological;Biology;cell age;Cell Aging;Cell Nucleus;Cell Physiology;Cells;Chromatin;Complex;Coupled;Cytoskeleton;Cytoskeleton Alteration;Defect;DNA Damage;Exhibits;Exploratory/Developmental Grant;Fibroblasts;Gene Expression;Genes;Genome;genome-wide;Goals;hallmarks of aging;insight;Investigation;Knock-out;Lamin Type A;life span;Light;Microtubules;Modeling;Modification;Morphology;Mus;mutant;normal aging;novel;Nuclear;Nuclear Envelope;overexpression;Pathologic;pathological aging;Patients;Phenotype;Physiological;Post-Translational Protein Processing;premature;Premature aging syndrome;Production;Progeria;promoter;Proteins;replication stress;Role;senescence;Shapes;Structure;Syndrome;Testing;Time;Translating;Tubular formation;Tubulin;Up-Regulation;Work;Writing

PROJECT_TITLE: Tubulin modifications and cytoskeletal alterations in aging

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative: Understanding the mechanisms of protein and organelle function and dysfunction in disease requires a detailed and dynamic analysis of molecular structures and interactions in live cells. The long-term goal of my laboratory is to develop tools that reveal these functional elements and apply them to discover significant biology and/or design molecules with useful properties. This application seeks support for three of the four areas we investigate, all of which depend the development and application of novel fluorescent tools.

PI_NAMEs: SCHEPARTZ, ALANNA  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Fluorescence tools that illuminate biology and inspire translation

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Emerging Infectious Diseases;Genetics;HIV/AIDS;Infectious Diseases;Orphan Drug;Prevention;Rare Diseases

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Project Narrative After 25 years there is still is no adequate animal model for Kaposi Sarcoma, which is the most common cancer in people living with HIV/AIDS world-wide. This proposal responds to NCI PQ6, to develop such a model for drug and vaccine testing.

PI_NAMEs: DITTMER, DIRK P (contact)

PROGRAM_OFFICER_NAME: READ-CONNOLE, ELIZABETH LEE

PROJECT_TERMS: Age;AIDS related cancer;Animal Model;Animals;Anniversary;antiretroviral therapy;Bypass;CD4 Lymphocyte Count;Cell Line;cell type;Cells;Cellular Structures;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;common treatment;Data;Development;DNA Damage;Doxorubicin;Doxorubicin Hydrochloride Liposome;drug candidate;drug development;Drug Modelings;drug testing;Evaluation;FRAP1 gene;Frequencies;Ganciclovir;Gene Expression Profile;Generations;Genes;Genetic Transcription;Genome;Germ Lines;Hemangiosarcoma;HIV;HIV Seronegativity;HIV/AIDS;Human;human fetus tissue;Human Herpesvirus 8;Immune;Immunocompetent;In Vitro;in vivo;in vivo Model;Incidence;Kaposi Sarcoma;Knowledge;Lesion;Lymphoma;Lytic;Malignant Neoplasms;Maps;Modeling;Molecular;Molecular Target;mouse model;mTOR Inhibitor;Mus;Neoplasm Transplantation;neoplastic cell;novel;novel therapeutics;Pathogenesis;Pathway interactions;permissiveness;Persons;Pharmaceutical Preparations;Phase;Platelet-Derived Growth Factor;pomalidomide;prevent;preventive intervention;Proteins;Regimen;Research;response;Safety;Signal Transduction;Structure;Study models;targeted treatment;Testing;Tissues;Transcript;Transgenic Mice;Transgenic Model;Transplantation;tumor;Tumor-Derived;tumorigenesis;vaccine development;vaccine evaluation;Vaccines;Vascular Endothelial Growth Factors;Viral;Viral Genes;Viral Genome;Viral Load result;Viral Oncogene;Virus Latency

PROJECT_TITLE: PQ6: Transgenic Mouse Model for Kaposi Sarcoma


ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Project Narrative Persons with HIV (HIV+) have a higher risk of developing metabolic diseases, such as type 2 diabetes or high cholesterol, compared to HIV-negative persons with similar age and body weight, but the reason for this difference in risk is not clear. Recent studies show that HIV infection and antiretroviral treatment can cause changes in subcutaneous adipose tissue (fat) which reduce its ability to store energy and lead to the accumulation of adipocytes (fat cells) around the internal organs, in the liver, and in other tissues. The goal of this study is to understand the factors leading to energy storage defects in subcutaneous adipose tissue and the excessive accumulation of fat in other organs, which could lead to therapies to reduce metabolic disease in both HIV+ persons and the general population.

PI_NAMEs: COLLINS, SHEILA ;KOETHE, JOHN  (contact);SILVER, HEIDI JAYE

PROGRAM_OFFICER_NAME: BASU, RAJATAVA

PROJECT_TERMS: Academic Medical Centers;adipocyte biology;Adipocytes;Adipose tissue;Age;antiretroviral therapy;Architecture;Automobile Driving;Body fat;Body Regions;Body Weight;Cardiometabolic Disease;cardiometabolism;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Cholesterol;Clinical;Clinical Research;comorbidity;cytotoxic;Data;Defect;density;Deposition;Development;Diabetes Mellitus;doubly-labeled water;energy balance;Energy Intake;Energy Metabolism;Environment;Fatty acid glycerol esters;fatty acid oxidation;Flow Cytometry;Functional disorder;Future;Gene Expression;General Population;Genes;Goals;high risk;HIV;HIV Infections;HIV Seronegativity;Human;Image;Immune;immune activation;Immunology;Impairment;Indirect Calorimetry;Inflammation;Inflammatory;inhibitor;Insulin Resistance;Integrase;Intervention Studies;Intra-abdominal;Link;lipid transport;Lipids;Liver;Longitudinal Studies;Measurement;Mediating;Metabolic;Metabolic Diseases;Metabolism;Modeling;Modernization;multidisciplinary;Non-Insulin-Dependent Diabetes Mellitus;nutrition;Obesity;Organ;Pathway interactions;Persons;Pharmacologic Substance;Physiology;prevent;Procedures;radiological imaging;Regimen;Risk;Risk Reduction;Role;Science;Skeletal Muscle;subcutaneous;Suction Lipectomy;T-Lymphocyte;T-Lymphocyte Subsets;Technology;Testing;Tissues;transcriptomics;Transferase;Triglycerides;Viral;Visceral;Weight;Weight Gain;X-Ray Computed Tomography

PROJECT_TITLE: Pathophysiology of Metabolically Detrimental Changes in Adipose Distribution, Adipocyte Function, and Adipose Immune Environment on Antiretroviral Therapy


ORG_CITY: EAST LANSING

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: MICHIGAN STATE UNIVERSITY

PHR: PROJECT NARRATIVE (RELEVANCE) This R01 proposal aims to develop a complete, diamond-based neural implant system that will consist of up to 256-channel recording electrodes in mm3-size volumes for combined electrophysiology and dopamine sensing from large-scale neuronal networks, with significantly enhanced sensitivity, specificity, and stability over existing technologies. The objectives of this proposal are consistent with the mission of the NIH, and will have a significant impact on public health by providing a novel neural interface tool for neuroscientists and clinical researchers to reveal the mechanisms underlying many brain disorders and diseases that are dopamine-dependent, such as Parkinson’s disease, schizophrenia, and drug addiction.

PI_NAMEs: LI, WEN  (contact)

PROGRAM_OFFICER_NAME: KUMSA, DOE WONDWOSSEN

PROJECT_TERMS: 3-Dimensional;Address;Adopted;Adult;Amplifiers;Behavior;Biocompatible Materials;biomaterial compatibility;Blood - brain barrier anatomy;Brain;Brain Diseases;Brain region;carbon fiber;Cell Death;Chemicals;Chemistry;Chronic;Cicatrix;Clinical;Clinical Research;Communities;Complex;Computer software;Corpus striatum structure;cost efficient;data acquisition;Data Analyses;data integration;density;design;Detection;detection limit;Development;Device Designs;Devices;Diamond;Dimensions;Dopamine;Drug Addiction;electric impedance;Electrochemistry;Electrodes;electron beam lithography;Electronics;Electrophysiology (science);Encapsulated;Engineering;experience;extracellular;fabrication;Fiber;Film;flexibility;fundamental research;Future;Geometry;Goals;Hand;Head;Hybrids;Immunohistochemistry;Implant;implantation;Implanted Electrodes;in vivo;Individual;Inflammation;innovation;instrument;large scale production;Lateral;Light;lithography;Longevity;manufacture;Maps;Measurement;mechanical properties;Mechanics;meter;Microelectrodes;millisecond;Miniaturization;miniaturize;minimally invasive;Mission;Monitor;Morphology;multidisciplinary;nanofabrication;Nerve Tissue;neural;neural implant;neurochemistry;Neurologic;Neurons;neurophysiology;Neurosciences;Neurotransmitters;Noise;North Carolina;novel;operation;Parkinson Disease;Performance;Periodicity;Property;Public Health;Rattus;Research Personnel;Resolution;response;Safety;Scanning;Schizophrenia;Semiconductors;sensor technology;Signal Transduction;Site;spatiotemporal;Specificity;study characteristics;submicron;Surface;System;Systems Integration;Techniques;technological innovation;Technology;Time;tool;two-dimensional;ultraviolet;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: Microfabricated all-diamond microelectrode arrays for neurotransmitter sensing and extracellular recording

STUDY_SECTION: BNVT

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


ORG_CITY: TALLAHASSEE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: FLORIDA STATE UNIVERSITY

PHR: Adiponectin is a protein that circulates in high levels in the blood and which has known protective effects on the cardiovascular system. Aging impairs vascular function, but late-life exercise can reverse much of the vascular dysfunction related to advancing age. The overall goal of this application is to determine whether adiponectin plays a role in 1) the vascular dysfunction that occurs with advancing age, and 2) the ability of exercise training to promote vascular resiliency and reverse age-related vascular dysfunction.

PI_NAMEs: DELP, JUDY M (contact)

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: Acute;adiponectin;Adjuvant;Aerobic Exercise;Age;age related;aged;Aging;Agonist;antagonist;arterial remodeling;Arteries;Biomedical Research;Blood;Blood flow;blood pressure regulation;Blood Vessels;cardiac vasculature;Cardiovascular Diseases;cardiovascular effects;Cardiovascular system;Ceramides;Coronary;Development;Disease;Elderly;Elements;endothelial dysfunction;Endothelium;Exercise;exercise training;Functional disorder;gain of function;Germ Lines;Goals;Impairment;improved;Inflammation;Knock-out;late life;life span;loss of function;Microvascular Dysfunction;middle age;mimetics;Mus;Myocardium;novel;Organ;pathological aging;pharmacologic;Phenotype;Prevention;promote resilience;protective effect;Proteins;Rattus;receptor;Reporting;Research Priority;resilience;Resistance;response;Risk Factors;Role;sedentary;senescence;Signal Pathway;Signal Transduction;Skeletal Muscle;Smooth Muscle;Sphingosine;Structure;Testing;therapeutic target;Training;Vascular Diseases;Vascular remodeling;Vascular Smooth Muscle;Vasomotor;Work;young adult

PROJECT_TITLE: Role of Adiponectin in Reversal of Age-related Vascular Dysfunction

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Dental, Oral, and Craniofacial Disease;Genetics;Infectious Diseases;Neurosciences

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Many infectious complications following craniotomy are attributed to Staphylococcus aureus (S. aureus) biofilm, which are debilitating due to their chronicity. We will examine how T cells that enter the infected brain promote the antibacterial activity of innate immune cells to contain S. aureus growth. In addition, we will examine how T cells cause S. aureus adaptation to escape immune-mediated clearance and establish craniotomy infection. A better understanding of how biofilms regulate inflammatory activity will guide the development of future immune- based strategies for the treatment of craniotomy infections.

PI_NAMEs: KIELIAN, TAMMY L (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Address;Aneurysm;Animals;Anti-Bacterial Agents;anti-microbial peptide;Antibacterial Response;Antibiotics;Antibodies;Antigens;antimicrobial;Attenuated;Bacteria;bactericide;Binding;bone;Brain;Burr hole procedure;CD4 Positive T Lymphocytes;Cell Shape;Cells;Cellular Metabolic Process;Cephalic;Chronic;chronic infection;Clip;Containment;Craniotomy;cranium plastic repair;CXCL10 gene;Data;Development;effector T cell;Epilepsy;Excision;experimental study;Exposure to;Future;Gene Expression Profile;Genes;Genetic Transcription;Goals;granulocyte;Growth;Human;human disease;humanized mouse;Hydrocephalus;Immune;Immune response;improved;Infection;Inflammatory;innovation;Interferon Type II;Invaded;Knockout Mice;Leucocytic infiltrate;leukocyte activation;Leukocytes;Macrophage;Magnetic Resonance Imaging;Mediating;Membrane;metabolic profile;Microbial Biofilms;Microglia;Molecular;monocyte;Morbidity - disease rate;mouse model;mutant;Myeloid-derived suppressor cells;Neurologic Dysfunctions;neutrophil;novel;novel strategies;Outcome;pathogen;Pathway interactions;Patients;Pattern;Phagocytes;Phagocytosis;Play;prevent;Procedures;Process;Production;Property;Prophylactic treatment;Proteins;Rag1 Mouse;recruit;Regulation;Reporting;Residual state;response;Risk;Role;Sampling;Seizures;Shapes;single-cell RNA sequencing;Specificity;Staphylococcal Protein A;Staphylococcus aureus;subcutaneous;Syndrome;T cell response;T-Cell Activation;T-Cell Depletion;T-Lymphocyte;Tissues;transcription factor;transcriptome;translational study;treatment strategy;tumor;Virulence;Virulence Factors;virulence gene

PROJECT_TITLE: T cell-innate immune crosstalk regulates Staphylococcus aureus craniotomy infection


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Clinical Research;Epilepsy;Genetics;Human Genome;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Pediatric;Prevention

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because the identification of genetic risk factors for outcome and medication response in childhood epilepsies is ultimately expected to translate into personalized medication choices and early identification of patients at risk for refractory epilepsy or a poor developmental outcome, and will increase understanding of biological mechanisms underlying childhood epilepsies. Thus, the proposed research is relevant to the purpose of the NIH Independent Scientist Award and mission of the NINDS by providing a tailored program to enhance the applicant’s skills for electronic medical record data analysis and large-scale genomic studies in order to use this knowledge to reduce the burden of neurological disease.

PI_NAMEs: HELBIG, INGO  (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Address;Age;age related;Algorithms;anti-epileptic agents;Award;biobank;Biological;Birth;Child;childhood epilepsy;Chromosome Mapping;Clinical;Clinical Course of Disease;Clinical Management;clinical practice;Cohort Studies;Complex;Computerized Medical Record;Computing Methodologies;Data;Data Analyses;Data Set;Data Sources;Development;Developmental Disabilities;Diagnostic;Disease;drug development;Early identification;Epilepsy;epileptic encephalopathies;exome;experience;Funding;Future;Gastaut syndrome;Genes;Genetic;Genetic Predisposition to Disease;genetic risk factor;Genetic study;genetic variant;Genomics;Genotype;Goals;Hospitals;Human;Independent Scientist Award;Individual;Infantile spasms;innovation;insight;Institution;Intractable Epilepsy;Joints;Knowledge;Link;Manuals;Maps;Methods;Mission;Multicenter Studies;Mutation;Myoclonic Astatic Epilepsies;National Institute of Neurological Disorders and Stroke;Neonatal;Nervous System Disorder;Neurology;novel;Ontology;Outcome;Outcome Assessment;Outcome Study;Pathway interactions;Patients;Pattern;Pharmaceutical Preparations;Phenotype;phenotypic data;phenotyping algorithm;prevent;Probability;programs;Public Health;rare variant;Recording of previous events;Research;Research Design;response;Risk;Seizures;skills;Syndrome;Techniques;Testing;Therapeutic;Therapeutic Intervention;therapy development;Training;Translating;treatment pattern;United States National Institutes of Health;Work

PROJECT_TITLE: Joint analysis of genomic and electronic medical record data to assess outcomes and drug response in pediatric epilepsies

STUDY_SECTION: NST

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


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Childhood Injury;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Emergency Care;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Mental Illness;Pediatric;Prevention;Social Determinants of Health;Suicide;Suicide Prevention;Violence Research;Youth Violence

ORG_CITY: PROVIDENCE

ORG_NAME: RHODE ISLAND HOSPITAL

ORG_STATE: RI

PHR: PROJECT NARRATIVE Suicidal thoughts and behaviors and non-suicidal self-injury are disproportionally high among justice involved youth (JIY). This study aims to collaborate with community mental health agencies who serve JIY to enhance the implementation of effective system-level interventions for detecting and treating non-suicidal self-injury and suicidal thoughts and behavior in justice-involved adolescents. This work has the potential to better understand what agency-specific factors facilitate the successful implementation of evidence-based assessment and treatment for suicidal JIY living in the community and will yield practice-relevant information regarding scalability, implementation, and dissemination of treatment in the community.

PI_NAMEs: KEMP, KATHLEEN  (contact);WOLFF, JENNIFER CHRISTINE

PROGRAM_OFFICER_NAME: MARRO, MARY ACRI

PROJECT_TERMS: access restrictions;Accident and Emergency department;Adherence;Administrator;Adolescent;Affect;Ambulatory Care;barrier to care;Behavior;Caregivers;Characteristics;Child;Client;Climate;Clinic;Clinical Trials;Cluster randomized trial;Communities;community collaboration;Community Practice;Computerized Medical Record;Consultations;court;court personnel;Data;design;Detection;Education;Effectiveness;Effectiveness of Interventions;Emergency Care;Enrollment;ethnic minority;evidence base;Evidence based intervention;Evidence based treatment;experience;Family;Feeling suicidal;follow up assessment;follow-up;General Population;Goals;health disparity;Health Personnel;Health system;Healthcare Systems;Imprisonment;Improve Access;improved;Inpatients;Intervention;Interview;Justice;juvenile justice system;Leadership;Legal Guardians;Measures;Mental Health;Mental Health Court;Mental Health Services;National Institute of Mental Health;Neighborhoods;non-suicidal self injury;Organization and Administration;organizational readiness;Outpatients;parental involvement;Parents;Patients;Phase;Population;post implementation;practice setting;Preparation;Prevention;Procedures;Process;Provider;provider factors;psychiatric emergency;psychiatric inpatient;Psychiatric therapeutic procedure;Psychiatry;psychoeducation;Public Health;Questionnaires;racial minority;Randomized;randomized trial;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;reducing suicide;Reporting;Research;Resources;response;Rhode Island;Risk;Safety;Secure;Site;standard care;Standardization;Structure;suicidal;suicidal adolescent;suicidal behavior;suicidal risk;Suicide;Suicide attempt;suicide rate;Supervision;System;Testing;therapy design;Time;Training;Training Programs;treatment as usual;treatment comparison;treatment strategy;United States Substance Abuse and Mental Health Services Administration;uptake;vulnerable adolescent;Work;Youth

PROJECT_TITLE: From Court to the Community: Improving Access to Evidence-Based Treatment for Underserved Justice-Involved Youth At-Risk for Suicide


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Brain Disorders;HIV/AIDS;Infectious Diseases;Neurosciences;Prevention

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Prevention of HIV-associated neurocognitive impairment (HIV-NCI) remains as an elusive therapeutic goal in HIV treatment because even early introduction of combined antiretroviral therapy (cART) gives incomplete protection to the brain. Brain injury can begin soon after initial HIV infection, and inclusion of a rapidly-acting neuroprotective agent with cART initiation as soon as possible after HIV infection is likely necessary for maximum brain protection. We have shown that dimethylfumarate, an FDA-approved drug used in the treatment of multiple sclerosis, shows promise as a suitable neuroprotective agent in the rhesus macaque model of early brain injury caused by immunodeficiency virus, which could lead to future neuroprotection studies in persons living with HIV.

PI_NAMEs: KOLSON, DENNIS LARRY (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Acute;Acute Brain Injuries;Address;AIDS prevention;Anti-Inflammatory Agents;antioxidant enzyme;Antioxidants;antiretroviral therapy;Astrocytes;Autopsy;Biological Markers;Blood Vessels;Brain;Brain Injuries;Brain region;Brain Stem;brain tissue;Cells;Cellular Infiltration;Chemotaxis;cohort;Corpus striatum structure;Dinucleotide Repeats;Disease Progression;DNA;Drug usage;Endothelium;Enzymes;FDA approved;Fumarates;Future;Genetic Variation;Glutamates;Goals;Heme;heme oxygenase-1;heme oxygenase-2;HIV;HIV Infections;HIV-associated neurocognitive disorder;Hour;Human;Image;Immune;immune activation;immune cell infiltrate;immunodeficiency;Immunologic Markers;In Vitro;in vitro testing;in vivo;Infection;Infiltration;Inflammation;Inflammatory Response;Injury;Link;Lymphoid Tissue;Macaca;Macaca mulatta;Macrophage;Macrophage Activation;Meninges;microbial;Microglia;Modeling;monocyte;multiple sclerosis treatment;Neurocognitive;neuroinflammation;Neuronal Injury;Neurons;neuroprotection;Neuroprotective Agents;Optics;oxidation;Oxidation-Reduction;oxidative damage;Oxidative Stress;Oxygenases;Pathway interactions;Patients;Pattern;Persons;Pharmaceutical Preparations;Pilot Projects;Plasma;prevent;promoter;Protein Isoforms;Proteins;Recovery;response;response to injury;Risk;Role;Signal Transduction;SIV;Structure of choroid plexus;Synapses;T-Lymphocyte;Terminal Disease;Testing;Therapeutic;Tissues;treatment strategy;Variant;Viral load measurement;Virus;Virus Replication

PROJECT_TITLE: Protection against early SIV brain injury with adjunctive therapy to cART

STUDY_SECTION: HCCS

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


NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Infectious Diseases;Neurodegenerative;Neurosciences;Sexually Transmitted Infections

ORG_CITY: MADISON

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: Project Narrative HSV-1 infection is a known cause of secondary glaucoma and the only treatment options for the disease include reducing elevated pressure and inflammation in the eye. However, patients are sometimes resistant to current established treatments, and it is crucial to develop new treatments that can lower pressure and prevent recurrent HSV-1 reactivation. This study will examine the role of elevated intraocular pressure and damage to the drainage structures in the eye initiating the reactivation of HSV-1 and will provide a molecular understanding of recurrent HSV-1 reactivation in the eye, which may lead to better treatments for uveitic glaucoma.

PI_NAMEs: MCDOWELL, COLLEEN MARY (contact)

PROJECT_TERMS: Address;anterograde transport;aqueous;Aqueous Humor;Blindness;Cell Culture Techniques;Cell Line;Cell model;Cells;Cornea;Development;Disease;Drainage procedure;Eye;Eye Development;Eye diseases;Family;Fibronectins;Ganglia;Genome;Glaucoma;Goals;Herpes Simplex Infections;Herpesvirus 1;Human;Impairment;In Vitro;in vivo;Infection;Inflammation;Inflammatory;Knowledge;latent infection;Ligands;Modeling;Molecular;Mus;Nerve;nerve damage;Neurons;novel;Ocular Hypertension;Open-Angle Glaucoma;Optic Nerve;optic nerve disorder;Oryctolagus cuniculus;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Pattern;Peripheral;Peripheral Nerves;Phenotype;Physiologic Intraocular Pressure;pressure;prevent;Primary Infection;Production;Proteins;reactivation from latency;receptor;Recurrence;Resistance;response;retrograde transport;Risk;Risk Factors;Role;Signal Transduction;stressor;Structure;Structure of ciliary ganglion;Structure of trigeminal ganglion;Syndrome;Testing;Tissues;TLR4 gene;Trabecular meshwork structure;Transforming Growth Factor beta;Viral Genes;Virus;Virus Activation

PROJECT_TITLE: HSV-1 reactivation and glaucomatous trabecular meshwork damage

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


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Clinical Research;Genetics;Human Genome;Multiple Sclerosis;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: Project Narrative In this project, we will identify the critical cell populations and cell-to-cell communications in multiple sclerosis lesions that are responsible for inflammation and tissue repair in different disease stages.

PI_NAMEs: PITT, DAVID  (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Accounting;Acute;Antibodies;Astrocytes;Atlases;Biological;Cell Communication;Cell Nucleus;cell preparation;cell type;Cells;Chronic;Complex;computerized tools;Computing Methodologies;Data;Data Analyses;Data Set;data visualization;Demyelinations;denoising;Disease;Environment;Evaluation;Exhibits;Frequencies;Gene Expression Profile;Genetic Transcription;genomic platform;Heterogeneity;histological image;histological stains;Histology;Image;imaging approach;imaging modality;Imaging Techniques;immune cell infiltrate;improved;In Situ;In Vitro;Indirect Immunofluorescence;Inflammation;Inflammatory;innovation;insight;Lesion;Ligands;Lymphocyte;Maps;Microglia;Multiple Sclerosis;Multiple Sclerosis Lesions;multiplexed imaging;Myeloid Cells;Neurons;novel strategies;Nuclear;oligodendrocyte progenitor;Oligodendroglia;Organ;Pathologic;Pathology;Population;population based;Population Heterogeneity;precursor cell;Preparation;Protocols documentation;receptor;receptor expression;Recovery;Relapse;remyelination;Resolution;Resources;Sampling;Signal Transduction;single nucleus RNA-sequencing;Sorting;Spatial Distribution;Structure;Techniques;Testing;therapeutic target;tissue repair;Tissues;tool;transcriptome;transcriptomics;white matter

PROJECT_TITLE: Generating spatial and functional maps of cell-to-cell interactions in MS lesions


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Aging;Neurosciences

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: PROJECT NARRATIVE The age-associated decline in physical function increases the risk of frailty and chronic disease and shortens the healthy lifespan. Several clinical studies have demonstrated strong associations between elevated kynurenine levels and frailty/physical function in older adults. Using modern genetic models in rodents, this proposal will examine a direct causal link between elevated kynurenine, the aryl hydrocarbon receptor, and exacerbated age-dependent decline in physical function.

PI_NAMEs: HEPPLE, RUSSELL T;RYAN, TERENCE E (contact)

PROGRAM_OFFICER_NAME: BOYCE, AMANDA T

PROJECT_TERMS: Acceleration;age acceleration;age related decline;Aging;Agonist;antagonist;Aryl Hydrocarbon Receptor;aryl hydrocarbon receptor ligand;Atrophic;Attenuated;Binding;Blood;Body Weight;Catabolism;Cells;Chronic;Chronic Disease;Clinical;Clinical Research;Coupled;Cytochrome P450;Cytosol;Data;Denervation;Dependence;Deterioration;Diet;Dimensions;Disease;Drug Metabolic Detoxication;drug testing;Elderly;Enzymes;epidemiology study;exercise training;Exposure to;FDA approved;Foundations;Frail Elderly;frailty;Functional disorder;Future;Genetic Models;Goals;GOT2 gene;hallmarks of aging;Hand Strength;Health;healthspan;healthy aging;Human;Impairment;In Situ;indexing;Individual;inhibitor;knock-down;Knock-out;Knockout Mice;Kynurenic Acid;Kynurenine;Kynurenine-oxoglutarate aminotransferase;Learning;Life Expectancy;Ligands;Link;loss of function;Metabolic;Metabolic Biotransformation;Metabolism;Mitochondria;mitochondrial dysfunction;Modeling;Modernization;Morbidity - disease rate;mortality;Motor;Motor Neurons;Mus;Muscle;muscle aging;Muscle Fibers;muscle form;Muscular Atrophy;neuromuscular;Neuromuscular Junction;neuron loss;neuroprotection;normal aging;older adult;Outcome;Oxidative Phosphorylation;Pathway interactions;Phenotype;Physical Function;Physiological;poor health outcome;Predisposition;Protein Isoforms;Proteolysis;Quality of life;Reactive Oxygen Species;Receptor Activation;Reporting;Research;Resveratrol;Risk;Rodent;Role;sarcopenia;Skeletal Muscle;skeletal muscle wasting;stressor;Testing;therapeutic target;Tissues;Transcript;transcription factor;Tryptophan;Tryptophan Metabolism Pathway;walking speed;Work

PROJECT_TITLE: Linking kynurenine accumulation and the AHR pathway to exacerbated aging


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Prevention;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

PHR: Project Narrative Mutations in dozens of different genes cause photoreceptor degeneration and blindness, but there is currently no effective therapy for these disorders. In this proposal we will develop a novel strategy to prevent blindness which utilizes CRISPR-Cas9 technology to knock out a key photoreceptor transcription factor, thereby suppressing photoreceptor degeneration. We believe that this new therapy will be applicable to multiple genetically distinct forms of blindness.

PI_NAMEs: CORBO, JOSEPH  (contact);KEFALOV, VLADIMIR JIVKOV

PROGRAM_OFFICER_NAME: SHEN, GRACE L

PROJECT_TERMS: Acute;Adult;Adverse effects;Affect;Animal Disease Models;Animal Model;Behavioral;Behavioral Assay;behavioral phenotyping;Biological Assay;Blindness;Candidate Disease Gene;candidate selection;Cell Reprogramming;cell type;Cells;Cessation of life;Clinical Research;Cone;CRISPR/Cas technology;Data;Dependovirus;Development;Disabling;Disease;disease model;Disease Progression;effective therapy;effectiveness testing;efficacy evaluation;Electron Microscopy;Electrophysiology (science);Functional disorder;Future;Gene Expression;Gene Expression Profiling;Genes;Genetic;Genetic Heterogeneity;Goals;Histologic;Human;Hybrid Cells;Immunohistochemistry;inherited retinal degeneration;Knock-out;Light;Mediating;Modeling;Molecular;Morbidity - disease rate;Morphology;Motivation;mouse model;Mus;Mutation;neuroprotection;new therapeutic target;novel;novel strategies;novel therapeutics;overexpression;Patients;Persons;photoreceptor degeneration;Photoreceptors;Physiological;preservation;prevent;Retinal Degeneration;Retinal Dystrophy;retinal rods;Retinitis Pigmentosa;rho;Rod;Source;Structure;targeted treatment;Testing;Therapeutic;transcription factor;transcriptome sequencing;Treatment Efficacy;Vision;Vision research;Wild Type Mouse;Work

PROJECT_TITLE: Targeting Nr2e3 to prevent photoreceptor degeneration