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

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: PROJECT NARRATIVE We discovered a new constituent of the quintessential SCF/c-Kit signaling pathway, Samd14, regulates erythroid progenitor function during regeneration. This project will advance our mechanistic understanding of the relationship between Samd14 and SCF/c-Kit signaling in erythroid regeneration, and establish completely unique stress-responsive mechanisms, with potentially-important therapeutic implications.

PI_NAMEs: HEWITT, KYLE J (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Acceleration;actin capping protein;Acute;Anemia;Biology;bone marrow failure syndrome;C-terminal;Cell Survival;Cells;Chronic;Clinical;cohort;Complex;conditional knockout;CRISPR/Cas technology;Data;diagnostic biomarker;Dysmyelopoietic Syndromes;Elements;Engineering;Enhancers;Erythrocytes;Erythroid;Erythroid Progenitor Cells;Erythropoiesis;Etiology;Exhibits;Functional disorder;GATA2 transcription factor;Gene Activation;gene network;gene regulatory network;Genes;Genetic;Genetic Models;Hematological Disease;Hematology;Hematopoiesis;Hemolytic Anemia;Human;Impairment;innovation;knock-down;Knock-out;knockout gene;Knowledge;Mediating;Modeling;Molecular;mouse genetics;mouse model;Mus;N-terminal;Natural regeneration;Non-Malignant;novel;novel therapeutics;Pathway interactions;Phenotype;Physiological;Production;progenitor;Property;protein protein interaction;Proteins;Proto-Oncogene Protein c-kit;regenerative;Regenerative response;Regulatory Element;response;SAM Domain;Signal Pathway;Signal Transduction;Site;small hairpin RNA;stem cell function;Stress;System;Tertiary Protein Structure;Testing;Therapeutic;therapeutic biomarker;transcription factor

PROJECT_TITLE: GATA Factor Mechanisms in Erythroid Regeneration

STUDY_SECTION: MCH

STUDY_SECTION_NAME: Molecular and Cellular Hematology Study Section[MCH]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Neurosciences;Orphan Drug;Precision Medicine;Prevention;Radiation Oncology;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: LOS ANGELES

ORG_COUNTRY: UNITED STATES

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: Project Narrative This proposal will study novel combination therapies against glioblastoma. It targets a pathway glioma cells use to escape radiotherapy and aims to uncover novel ways to improve the efficacy of radiation treatment for glioblastoma patients.

PI_NAMEs: PAJONK, FRANK  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: 3-Dimensional;Affect;Basic Science;Biological Assay;Biological Markers;Biology;biomarker identification;biomarker validation;blood-brain barrier crossing;cancer cell;cancer stem cell;Cancer Therapy Evaluation Program;Cell Differentiation process;Cells;chemotherapeutic agent;Cholesterol;cholesterol biosynthesis;Clinical;Clinical Trials;Clonal Evolution;Combination Drug Therapy;Combined Modality Therapy;Data;Disease;disorder control;Dose;drug development;Drug Interactions;Drug Kinetics;effective therapy;Electromagnetic Energy;Fatty Acids;Gene Expression Profiling;Generations;Glioblastoma;Glioma;Goals;Hypoxia;imaging system;improved;In Vitro;in vivo;induced pluripotent stem cell;inhibitor;innovation;Level of Evidence;Literature;Malignant Breast Neoplasm;Malignant neoplasm of brain;Malignant Neoplasms;Metabolic;mevalonate;Modality;Modeling;mouse model;neoplastic cell;nerve stem cell;nestin protein;neurogenesis;Nitric Oxide;novel;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phenotype;Population;prevent;Process;Publishing;Radiation;Radiation Dose Unit;Radiation Oncology;radiation resistance;Radiation therapy;radioresistant;Recurrence;Reporting;Resources;responders and non-responders;Scheme;self-renewal;Specimen;standard of care;stem cells;Surgical Oncology;synergism;targeted agent;targeted treatment;temozolomide;Testing;therapy outcome;therapy resistant;Time;tool;Toxic effect;trait;Transgenic Mice;Treatment Failure;tumor;tumor initiation;United States National Institutes of Health

PROJECT_TITLE: Use of CTEP portfolio compounds to counteract phenotype conversion in GBM

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: DURHAM

ORG_DEPT: PEDIATRICS

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative Effective and long lasting antibody responses, which require delicate collaboration of both T and B cells, is essential for immune responses to antigens and successful vaccinations against microbial infections. Using our newly generated mouse models either carrying a CVID patient-derived mutation in SBNO2 or being conditionally deficient of Sbno1, Sbno2, or both, we will illustrate novel mechanisms that control T cell development, homeostasis, and function to shape antibody and anti-viral immune responses. By illustrating the importance of Sbno1/2 in T cells, we will provide novel insight into mechanisms underlying T cell biology and CVID that will guide the development of novel therapeutic strategies against immune-related disorders.

PI_NAMEs: ZHONG, XIAOPING  (contact)

PROGRAM_OFFICER_NAME: MALLIA, CONRAD M

PROJECT_TERMS: Ablation;Adult;Affect;Antibodies;Antibody Response;Antigens;B cell differentiation;B-Cell Development;B-Lymphocytes;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;cell mediated immune response;Cell Physiology;Cell Survival;Cellular biology;Cessation of life;Child;Collaborations;Common Variable Immunodeficiency;conditional knockout;congenital immunodeficiency;Data;Development;Disease;Drosophila genus;Embryonic Development;Exons;Eye Development;Family;Gene Expression;Genes;Genetic Transcription;Homeostasis;Homologous Gene;Immune;Immune response;Immune system;Immune System Diseases;Immunity;immunodeficiency;immunoregulation;Impairment;improved;Infection;insight;Knockout Mice;Leg;LoxP-flanked allele;Mammals;Mediating;Memory;microbial;Missense Mutation;mouse model;Mus;Mutation;notch protein;novel;novel therapeutic intervention;Nuclear Proteins;Oogenesis;Pathogenesis;Pathway interactions;Patients;Physiological;prevent;Proliferating;prophylactic;Proteins;Reactive Oxygen Species;Recurrence;Regulation;response;RNA Helicase;Role;Shapes;Strawberries;Structure;Structure of germinal center of lymph node;T-Cell Development;T-Lymphocyte;Therapeutic;Thymus Gland;Vaccination;Viral;virtual;Virus Diseases;whole genome;Wing

PROJECT_TITLE: Strawberry notch homologues in T cell homeostasis and function

STUDY_SECTION: CMIA

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


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biotechnology;Childhood Obesity;Chronic Liver Disease and Cirrhosis;Clinical Research;Diabetes;Digestive Diseases;Genetics;Liver Disease;Nutrition;Obesity;Pediatric;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative / Public Health Relevance This project aims to characterize the genetics and molecular biology of a new insulin resistance syndrome associated with overgrowth called insulin-mediated pseudoacromegaly. FGF21 signaling is an exciting area of biology as it promotes insulin sensitivity while simultaneously promoting weight loss. The model systems created in this study will allow us to test drugs that not only have relevance for the patient described in this study, but also for the millions of individuals suffering from the consequences of obesity, type 2 diabetes, and metabolic syndrome.

PI_NAMEs: STONE, STEPHEN ISAAC (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: adipocyte differentiation;Adipocytes;Adipose tissue;Animals;APOA5 gene;apolipoprotein C-II;Area;autocrine;Biological Assay;Biological Markers;Biological Models;Biology;Biometry;Blood;Body Composition;Body Size;Body Weight decreased;Brown Fat;career development;Case Study;Cell Line;Childhood;Clinical;clinical training;Communication;Complex;CRISPR/Cas technology;Data;Diabetes Mellitus;dietary;Disease;disease model;Down-Regulation;drug testing;Endocrinology;Environment;Environmental Risk Factor;Epidemic;exome sequencing;experience;Fatty acid glycerol esters;Fatty Liver;fatty liver disease;Fellowship;Female Adolescents;Fibroblast Growth Factor;fibroblast growth factor 21;Fibroblast Growth Factor Receptor 1;Fibrosis;Foundations;functional genomics;Funding;Future;Genes;Genetic;genetic approach;genome editing;Genomic approach;Genomics;Glucose;glucose uptake;GLUT 4 protein;Goals;Growth;Healthcare;Hepatic;Hormones;Human;Hyperglycemia;Hyperinsulinism;IGF1 gene;Impairment;improved;In Vitro;in vivo;Individual;induced pluripotent stem cell;Inflammation;Insulin;Insulin Resistance;insulin sensitivity;Investigation;K-Series Research Career Programs;Ketone Bodies;Knock-in Mouse;Knowledge;laboratory experience;Lead;Link;lipid metabolism;Lipodystrophy;Lipolysis;Literature;Liver;Measurement;Measures;Mediating;Mentors;Metabolic;Metabolic syndrome;Molecular;Molecular Biology;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;Nonesterified Fatty Acids;novel;Obesity;Parents;Pathogenicity;Patients;Pattern;Pediatric Hospitals;Pediatrics;pharmacologic;Phenotype;Physicians;Play;Principal Investigator;proband;public health relevance;rare condition;Rare Diseases;receptor;Recombinant Fibroblast Growth Factor;Research;Research Ethics;Residencies;Resistance;response;Role;Scientist;Serum;Siblings;Signal Transduction;skills;SLC2A1 gene;Starvation;Syndrome;Testing;Therapeutic Agents;Training;transcription factor;Transgenic Mice;Transgenic Organisms;Triglycerides;United States;Universities;Variant;Washington;Work

PROJECT_TITLE: Using a Rare Disease Model to Explore the Role of FGF21 in Insulin Resistance

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


ADMINISTERING_IC: AG

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Physical Activity;Prevention;Social Determinants of Health

ORG_CITY: ANN ARBOR

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Regular physical activity is one of the most important predictors of healthy independent living, but the number of older adults meeting recommended guidelines remains low, especially in lower income communities. This project proposes career development to assist the candidate in developing and testing feasibility of a social network-based physical activity intervention in an affordable (HUD subsidized) senior housing community. This project is the first step in developing a novel low-cost intervention that will work with naturally occurring social resources to increase physical activity in lower income communities and reduce health disparities.

PI_NAMEs: WEBSTER, NOAH JAMES (contact)

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: Address;Affect;behavior change;behavior influence;Behavior Therapy;behavioral health;career;career development;Certification;Characteristics;Committee Members;Communities;community setting;contagion;cost;Data;efficacy trial;Environment;Evaluation;Event;evidence base;exercise intervention;Feasibility Studies;feasibility testing;Frequencies;Goals;Guidelines;Health;Health behavior;health disparity;Health Educators;Health Status;Housing;human old age (65+);implementation intervention;implementation process;improved;Independent Living;Influentials;Information Dissemination;Institute of Medicine (U.S.);Intervention;intervention cost;Intervention Studies;late life;Link;Low income;Measures;Medical;medical schools;meetings;Mentors;Methods;Michigan;Modeling;Monitor;Network-based;novel;older adult;Outcome;Pathway Analysis;Patient Self-Report;Persons;Physical activity;Physical assessment;Process;Psyche structure;Public Health;rate of change;Recommendation;Reduce health disparities;Reporting;Research;Research Activity;Resource-limited setting;Resources;Science;Scientist;Site;social;social engagement;social interventions;Social Network;social network intervention;social science research;Social Sciences;Social support;socioeconomics;Structure;Surveys;Testing;theories;therapy development;Training;Universities;wearable device;Work

PROJECT_TITLE: Leveraging social networks: a novel physical activity intervention for senior housing

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Behavior and Social Science of Aging Study Section[NIA-S]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: SEATTLE

ORG_NAME: VA PUGET SOUND HEALTHCARE SYSTEM

ORG_STATE: WA

PHR: Obstructive sleep apnea (OSA) is an obesity-related condition that affects 1.3 million Veterans, reduces quality of life, and is associated with greater risk of cardiovascular disease. Despite the potential of weight loss to reverse OSA, real-world impact is limited. Veterans seldom receive weight loss services due to a lack of counseling and poor accessibility of current weight loss offerings. Furthermore, there is uncertainty around the benefits of modest weight loss in achieving meaningful outcomes in OSA. To overcome access and knowledge gaps, this trial will examine the effectiveness of a population health approach to weight loss care among Veterans with OSA. We will use a remote lifestyle-based weight loss intervention that is self-directed, low- technology, and likely low cost. We propose a pragmatic trial of proactively delivering this novel intervention among patients with newly diagnosed OSA. We will test whether such an intervention improves weight and meaningful outcomes including sleep-related quality of life, sleep symptoms, and cardiovascular risk.

PI_NAMEs: DONOVAN, LUCAS MATTHEW (contact)

PROJECT_TERMS: Address;Adopted;Adoption;Affect;Agreement;Apnea;behavior change;Blood Pressure;Body Weight decreased;budget impact;cardiovascular disorder risk;cardiovascular risk factor;Caring;Characteristics;clinical practice;comorbidity;cost;Counseling;Data;design;diabetes prevention program;Diagnosis;Diet;Disease;Disease Management;Effectiveness;effectiveness evaluation;effectiveness outcome;effectiveness testing;efficacy trial;empowerment;Ensure;Family;follow-up;Future;Geography;Goals;Health;Health Promotion;Healthcare;Healthcare Systems;high risk population;Hybrids;implementation barriers;implementation outcomes;implementation process;Improve Access;improved;improvement on sleep;indexing;innovation;Internet;Intervention;Knowledge;Life Style;lifestyle intervention;Link;literacy;Lung;Maintenance;Measures;medical specialties;Methodology;Modeling;Modernization;Nature;neglect;Newly Diagnosed;novel;Obesity;Obstructive Sleep Apnea;Outcome;outcome prediction;Paper;Participant;Patients;Personal Satisfaction;Persons;Physiological;Policies;Population;population health;positive airway pressure;pragmatic trial;Prevention;primary endpoint;primary outcome;process evaluation;programs;Provider;Qualitative Methods;Quality of life;Randomized;Randomized, Controlled Trials;Reach, Effectiveness, Adoption, Implementation, and Maintenance;remote intervention;Research;Research Design;Resources;Risk;Risk Factors;Schedule;secondary outcome;Self Direction;Service delivery model;Services;Severities;Sleep;Symptoms;System;Technology;telecoaching;telehealth;telephone coaching;Testing;Time;Time trend;tool;Translating;treatment as usual;Uncertainty;Veterans;virtual healthcare;Visit;Weight;Weight Gain;weight loss intervention;weight loss program;Weight maintenance regimen;Work

PROJECT_TITLE: Pragmatic Obstructive Sleep Apnea Weight Loss Trial Assessing Effectiveness and Reach (POWER)

STUDY_SECTION_NAME: HSR-1 Health Care and Clinical Management[HSR1]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Genetics;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BURLINGTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: NARRATIVE Newly identified regulatory elements across the genome designated as “super enhancer domains” (SEDs) have highly specialized functions in controlling commitment of stem cells to development of a specific cell lineage. The proposed research will, for the first time, characterize SEDs that establish the bone forming osteoblast lineage. These novel genomic regions provide the basis for development of strategies in future studies to regenerate bone tissue in skeletal disorders.

PI_NAMEs: LIAN, JANE B.;STEIN, GARY S. (contact);STEIN, JANET L

PROGRAM_OFFICER_NAME: WAN, JASON

PROJECT_TERMS: Acetylation;Acute;Affect;Aging;Alkaline Phosphatase;Binding;Biological Assay;bone;Bone Development;Bone Formation Stimulation;bone loss;Bone Regeneration;Bone Surface;Bone Tissue;CCCTC-binding factor;Cell Lineage;Cell Separation;Cells;Chromatin;Chromatin Structure;chromosomal location;Chromosome Mapping;Chromosomes;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Competence;Complex;Control Groups;CRISPR/Cas technology;Data Set;Development;differential expression;Dimensions;Enhancers;Epigenetic Process;Female;functional genomics;Future;Gene Expression;Gene Expression Regulation;gene network;Genes;Genetic Transcription;Genome;Genomic Segment;Genomics;Hi-C;Higher Order Chromatin Structure;Histology;histone modification;Impairment;Implant;in vivo;in vivo evaluation;Injections;Intervention;Knowledge;Link;male;Maps;Mature Bone;Mediating;Mesenchymal Stem Cells;MicroRNAs;Modeling;Modification;mouse model;Mus;novel;osteoblast differentiation;Osteoblasts;Osteogenesis;osteogenic;Outcome;Ovariectomy;Phenotype;Prevention strategy;programs;protein complex;Publishing;Regulatory Element;Research;Resolution;Role;Selection Criteria;skeletal disorder;Specific qualifier value;stem cells;subcutaneous;Supporting Cell;Testing;Therapeutic;Time;Tissues;transcription factor;Transcriptional Regulation;transcriptome sequencing;translational applications;Transplantation;treatment strategy;Undifferentiated

PROJECT_TITLE: Chromatin Organization Regulates Osteogenesis

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


ADMINISTERING_IC: DA

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_CITY: FORT WORTH

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR

ORG_STATE: TX

PHR: Project Narrative (Public Health Relevance): Chronic pain, drug addiction, anxiety and depression each extract substantial health and socioeconomic costs from the American populace. Although drugs directed toward the kappa opioid receptor (KOR) have been investigated as treatments for these human ailments, they are currently hampered by poor side effect profiles. A deeper understanding of the mechanisms by which the proteins RGS12 and β-arrestin2 regulate the beneficial versus detrimental effects of KOR-directed drugs will enable new strategies to maximize the clinical utility of these (and future) drugs that provide pain relief by targeting opioid receptors, but without addiction or side effect liabilities.

PI_NAMEs: SIDEROVSKI, DAVID P. (contact)

PROGRAM_OFFICER_NAME: LE, HOANG VAN

PROJECT_TERMS: Ablation;Absence of pain sensation;Acceleration;Acute;addiction;Affect;Agonist;American;Amphetamines;Analgesics;antagonist;antinociception;Anxiety;Attenuated;Automobile Driving;Autoreceptors;Behavior;behavioral outcome;beta-arrestin;Biological Assay;Central Nervous System Diseases;Chronic;chronic pain;chronic painful condition;Clinical;clinically relevant;Cocaine;Complement;Complex;Corpus striatum structure;Cyclic AMP;Data;Data Correlations;Detection;Disease;Dopamine;Dopamine D2 Receptor;dopamine transporter;Drug Addiction;dysphoria;economic cost;Excision;Exhibits;Family member;Future;G-Protein-Coupled Receptors;GTP-Binding Protein Regulators;GTP-Binding Proteins;Guanosine Triphosphate Phosphohydrolases;Health;health economics;Heterotrimeric GTP-Binding Proteins;Human;In Vitro;in vivo;Individual;Intracellular Signaling Proteins;kappa opioid receptors;Knockout Mice;Locomotion;loss of function mutation;Measures;Mediating;member;Mental Depression;Molecular;Mouse Strains;mRNA Expression;mu opioid receptors;Mus;Mutation;Nature;Neurons;Nociception;novel;Opioid agonist;Opioid Receptor;Outcome;overexpression;pain relief;painful neuropathy;Pathway interactions;Patients;Pattern;Pertussis Toxin;Pharmaceutical Preparations;pharmacologic;Physiological Processes;Population;pre-clinical;preservation;presynaptic;protein activation;Protein Family;Proteins;Pruritus;psychostimulant;public health relevance;receptor;Receptor Activation;receptor expression;Receptor Signaling;receptor-mediated signaling;recruit;Regulation;Reporting;Research;response;reuptake;Role;side effect;Signal Pathway;Signal Transduction;Signaling Protein;Site-Directed Mutagenesis;socioeconomics;Spinal;Spinal Cord;Stress;success;Surface;Testing;Therapeutic;uptake;Validation;Ventral Striatum

PROJECT_TITLE: The role of RGS12 in differential modulation of G protein versus beta-arrestin signaling downstream of the kappa opioid receptor

STUDY_SECTION: MNPS

STUDY_SECTION_NAME: Molecular Neuropharmacology and Signaling Study Section[MNPS]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative A novel class of long non-coding RNAs that are continuous with and extend far downstream of their upstream protein-coding genes was recently discovered. These RNAs are produced upon innate immune activation from thousands of antiviral genes including the type I interferons, but their function remains elusive. By elucidating the mechanism by which these RNAs regulate the type I interferon response, this study may uncover a new mode of regulation of innate antiviral immunity by previously unappreciated RNA molecules.

PI_NAMEs: PARK, ANNSEA  (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Address;Affect;Anti-viral Response;antiviral immunity;Architecture;ATAC-seq;Autoimmune Diseases;Cell Nucleus;Cells;Cellular Stress;ChIP-seq;Chromatin;Chromatin Loop;Chromatin Modeling;chromatin remodeling;chromosome conformation capture;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Complex;Defense Mechanisms;Epigenetic Process;Equilibrium;Gene Expression;Genes;Genetic;Genetic Transcription;Genome;genome editing;genomic locus;Guide RNA;histone modification;Homeostasis;human disease;Human Genome;immune activation;immunopathology;improved;in vivo;Infection;innate immune sensing;insight;Interferon Activation;Interferon Type I;Interferon-beta;Interferons;knock-down;Knock-in Mouse;Malignant Neoplasms;mammalian genome;Measures;Mediating;Modeling;Molecular;Mus;Natural Immunity;novel;Nucleic Acids;Organism;Phenotype;Physiological;Post-Transcriptional RNA Processing;posttranscriptional;Process;programs;Proteins;Recombinant Interferon Beta;Regulation;response;RNA;Role;senescence;Serum;Signal Transduction;stressor;System;Systemic Lupus Erythematosus;Testing;Therapeutic;Tissues;Transcript;transcriptome;Transgenic Mice;Type I Interferonopathy;Untranslated RNA;Vesicular stomatitis Indiana virus;Viral;Viral Genes;viral resistance;Virus Diseases;Virus Replication

PROJECT_TITLE: A novel class of long non-coding RNA in regulation of the type I interferonresponse

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


ADMINISTERING_IC: OD

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

ORG_CITY: WORCESTER

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: Project Narrative – Overall Nonhuman primates (NHPs) play an important role as animal models of disease in basic and translational research. This program develops, manufactures and distributes immune cell-depleting antibody research reagents to optimize the usefulness of these animal models. These immune cell- depleting antibodies help investigators to develop treatments and vaccines for many different infectious diseases, and to improve methods of organ transplantation.

PI_NAMEs: ENGELMAN, KATHLEEN ;MAGNANI, DIOGO  (contact)

PROGRAM_OFFICER_NAME: CONTRERAS, MIGUEL A

PROJECT_TERMS: Advertising;Animal Disease Models;Animal Model;Antibodies;antibody engineering;Applied Research;Basic Science;Biological;Cell Physiology;Cells;Communicable Diseases;cytotoxicity;design;Disease;Genetic Polymorphism;Grant;Growth;Half-Life;Immune;Immune Targeting;immunomodulatory therapies;improved;in vivo;Infection;infectious disease model;Infrastructure;large scale production;manufacture;Measures;Methods;Modeling;nonhuman primate;novel therapeutics;novel vaccines;Online Systems;Organ Transplantation;Pathogenesis;Pharmaceutical Preparations;Play;Preclinical Testing;prevent;Program Effectiveness;programs;Quality Control;R24;Reagent;receptor;Reproducibility;Research;Research Personnel;Resources;Rhesus;Role;Testing;Therapeutic antibodies;Translational Research;United States National Institutes of Health;vaccine evaluation;Vaccines

PROJECT_TITLE: Nonhuman Primate Antibody Resource for Immune Cell Depletion

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GGG-D(50)R]


NIH_SPENDING_CATS: Biotechnology;HIV/AIDS

PI_NAMEs: MAGNANI, DIOGO  (contact)

PROJECT_TERMS: Animals;Antibodies;Buffers;Cells;Chinese Hamster Ovary Cell;Communities;Community Outreach;Core Grant;cross reactivity;disease model;Engineering;Ensure;Formulation;Funding Agency;glycosylation;Goals;Immune;immunogenicity;in vivo;manufacture;Marketing;Measures;meetings;Modeling;Monoclonal Antibodies;nonhuman primate;Online Systems;Primates;Process;Program Effectiveness;programs;Quality Control;Reaction Time;Reagent;Research;Research Personnel;Resources;Surveys;System;Transfection;Transgenic Mice;web platform

PROJECT_TITLE: Resource Core

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GGG-D]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Genetics;Human Genome;Women's Health Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative Frequently mutated or hyperactivated Notch receptors dysregulate transcription of genes with key functions in triple-negative breast cancer (TNBC), a heterogenous disease lacking targetable therapeutic options. My research elucidates precise epigenetic mechanisms by which Notch transcription complexes regulate their TNBC target genes. This mechanistic knowledge constitutes an important step toward selective epigenetic targeting of functionally important but “undruggable” genes such as MYC, CCND1 and SOX9 in the Notch-addicted TNBC. !

PI_NAMEs: FARYABI, ROBERT BABAK (contact)

PROGRAM_OFFICER_NAME: FINGERMAN, IAN M

PROJECT_TERMS: 3-Dimensional;Ablation;Binding;Biological Assay;Biological Markers;Breast Cancer Cell;Breast Cancer gene;Breast Cancer Patient;Breast Cancer Treatment;cancer genome;CCND1 gene;Cell division;Cell Physiology;Cells;Chemoresistance;Chromatin;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Data;Disease;disease heterogeneity;disorder subtype;DNA;Dominant-Negative Mutation;Drug resistance;Enhancers;Epigenetic Process;Frequencies;functional genomics;Future;Gene Activation;Gene Expression;Genes;Genetic Transcription;Genome;genome editing;genome-wide;Goals;Histones;Homeostasis;Hyperactivity;improved;Individual;inhibitor;Kinetics;Knowledge;Malignant Breast Neoplasm;Maps;Mediating;Molecular;Molecular Conformation;Mutate;Neoplasm Metastasis;notch protein;novel;Oncogenic;Patients;Pharmaceutical Preparations;Population;Positioning Attribute;Process;programs;promoter;protein expression;Proteins;Proto-Oncogenes;Regulation;Research;Resistance;Resolution;Role;secretase;Signal Transduction;SP1 gene;Subgroup;success;Survival Rate;targeted treatment;Technology;Testing;Therapeutic;therapeutically effective;Therapeutically Targetable;therapy resistant;transcription factor;triple-negative invasive breast carcinoma;tumor growth;Tumor Promotion;Zinc Fingers

PROJECT_TITLE: Notch-driven Epigenetic Program of MYC and CCND1 in Triple-Negative Breast Cancer

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Biotechnology;Genetics;HIV/AIDS

PI_NAMEs: ENGELMAN, KATHLEEN  (contact)

PROJECT_TERMS: Affect;Affinity;Alleles;Animals;Antibodies;Antibody Affinity;Applied Research;Biological Markers;biomarker identification;Candidate Disease Gene;case control;Cells;Data;design;Development;Dose;Effectiveness;Exclusion;experimental study;Failure;Fc Receptor;Gene Frequency;Generations;Genes;genetic association;Genetic Markers;Genetic Polymorphism;genetic variant;Genotype;Heterogeneity;Human;IgG Receptors;Immune;improved;in vivo;Ligands;Mediating;Monoclonal Antibodies;nonhuman primate;Outcome;Patients;Performance;Pharmaceutical Preparations;Population;predictive marker;programs;prospective;Reagent;receptor;Regimen;Research Personnel;Research Project Grants;Resources;response;Rhesus;Role;Specimen;success;targeted agent;Therapeutic;Treatment Efficacy;Treatment outcome;Variant

PROJECT_TITLE: Applied Research Project


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

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);Bioengineering;Biomedical Imaging;Brain Disorders;Cardiovascular;Cerebrovascular;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Racial and Ethnic Minority Health Research;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: POUGHKEEPSIE

ORG_DEPT: BIOLOGY

ORG_NAME: VASSAR COLLEGE

ORG_STATE: NY

PHR: Project Narrative Aging is associated with a dramatic increase in aortic stiffness and subsequent damage to other downstream organs. Since sustained cerebral blood flow is critical, the brain and the vessels of the brain are particularly at risk of injury as a result of higher aortic stiffness. This study will assess how higher levels of aortic stiffness and small vessel dysfunction contribute to early signs of dementia and vascular brain injury.

PI_NAMEs: COOPER, LEROY LEON (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: abeta accumulation;Academic achievement;African American;African American population;Aging;Alzheimer's Disease;Amyloid beta-Protein;Anisotropy;Aorta;Area;arterial tonometry;Award;Bioethics;Blood Vessels;Brain;Brain imaging;Brain Injuries;burden of illness;cardiovascular disorder epidemiology;Cardiovascular Physiology;Cardiovascular system;career development;career networking;caucasian American;Cerebral Infarction;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;Cerebrovascular system;Cerebrovascular Trauma;Clinical;Cohort Studies;Communities;Complement;Data;Dementia;digital;Disease Progression;electric impedance;Epidemiology;experience;Faculty;Femur;Framingham Heart Study;Functional disorder;Generations;Goals;Grant;health disparity;hemodynamics;Impaired cognition;indexing;Individual;Injury;innovation;Investigation;Jackson Heart Study;Link;Magnetic Resonance Imaging;Measures;Mediating;member;Memory;Mentors;Methods;Microvascular Dysfunction;multidisciplinary;Neurofibrillary Tangles;neurovascular;novel;Older Population;Organ;Participant;Peptides;Performance;Peripheral;Phase;Physiologic pulse;Physiology;Positron-Emission Tomography;pre-clinical;pressure;Prevention;Pulse Pressure;racial disparity;Reporting;Research;Research Activity;Research Personnel;Resistance;Risk;secondary analysis;tau Proteins;Testing;tonometry;Training;Training Activity;ultrasound;vascular abnormality;Vascular Dementia;vascular factor;vascular injury;Vascular remodeling;Water;white matter;White Matter Hyperintensity;Work;β-amyloid burden

PROJECT_TITLE: Vascular hemodynamics and markers of preclinical and subclinical vascular brain injury and dementia


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_NAME: SEATTLE INST FOR BIOMEDICAL/CLINICAL RES

PHR: PROJECT NARRATIVE  Pathogenic protein aggregates are present in most neurodegenerative diseases, and the spread of these aggregates within the brain correlates with disease progression. However, it remains poorly understood how these aggregates spread from neuron to neuron, and elucidating this process could reveal novel therapeutic targets to slow or halt neurodegeneration. This project investigates how mutations in GBA, a gene associated with faster progression of Parkinson's disease, influences propagation of protein aggregates from cell to cell in fruit fly, human neuron and mouse models of neurodegeneration.

PI_NAMEs: DAVIS, MARIE YNEZ (contact)

PROGRAM_OFFICER_NAME: SARRAF, SHIREEN AKHAVAN

PROJECT_TERMS: Acceleration;Acids;Affect;Alleles;alpha synuclein;Alzheimer's Disease;Biogenesis;Brain;Cell Aggregation;Cell Culture Techniques;Cell secretion;Cells;Ceramides;Clinical;Dementia with Lewy Bodies;Disease Progression;Drosophila genus;Enzymes;experimental study;extracellular vesicles;fly;Gaucher Disease;Genes;Genetic;genetic risk factor;Glucose;glucosidase;glucosylceramidase;Glucosylceramides;Heterozygote;Human;Impaired cognition;in vivo;induced pluripotent stem cell;Kinetics;Lead;Lewy body pathology;Link;lipid metabolism;lipidomics;Lipids;Lysosomal Storage Diseases;Mediating;Membrane;Metabolism;Modeling;Molecular Chaperones;Morphology;Motor;motor symptom;mouse model;Mus;Mutation;Nerve Degeneration;Neurobehavioral Manifestations;Neurodegenerative Disorders;Neuromuscular Junction;Neurons;neuropathology;new therapeutic target;novel;Parkinson Disease;Pathogenesis;Pathogenicity;Patients;Phenotype;prion-like;Process;Production;protein aggregation;Proteins;Proteomics;proteostasis;Reporter;Research;Risk;Role;stem cell model;Stereotyping;synaptotagmin;System;tau-1;Testing;Tissues;trafficking;Work

PROJECT_TITLE: Investigating the role of lipid metabolism in protein aggregation and neurodegenerative disease progression

STUDY_SECTION: SYN

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


NIH_SPENDING_CATS: Clinical Research;Genetics;Infectious Diseases;Malaria;Orphan Drug;Pediatric;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BETHESDA

ORG_NAME: HENRY M. JACKSON FDN FOR THE ADV MIL/MED

ORG_STATE: MD

PHR: Project Narrative New strategies are required to block the spread of malaria, which still is responsible for over 200 million clinical cases and the deaths of 0.43 million people each year. The goal of the project is to advance the understanding of the production of the transmission stage, the gametocyte.

PI_NAMEs: AMOAH, LINDA EVA;WILLIAMSON, KIM C (contact)

PROGRAM_OFFICER_NAME: RAO, MALLA R

PROJECT_TERMS: 15 year old;Africa;Age;Alleles;Anopheles Genus;Area;asexual;Biological Assay;Biological Markers;Blood;Blood specimen;Body Temperature;causal variant;Cessation of life;chemokine;Child;Circulation;Clinical;cohort;Collection;Culicidae;CX3CL1 gene;CXCL5 gene;Data;design;Development;differential expression;DNA analysis;Drug Targeting;Dryness;Environment;enzyme activity;Enzymes;Evaluation;Female;Fever;field study;Gene Deletion;Genes;Genotype;Ghana;Goals;high risk population;Histone Deacetylase;histone demethylase;Human;Immune response;Immunity;Immunologic Factors;Immunology procedure;In Vitro;in vivo;in vivo evaluation;in vivo monitoring;Individual;insight;interest;Intervention;Invaded;Life Cycle Stages;longitudinal analysis;longitudinal, prospective study;Lysine;Lysophosphatidylcholines;Malaria;malaria transmission;male;Measurement;Metabolic;metabolomics;Monitor;Morphology;Mutation;novel therapeutics;novel vaccines;Parasitemia;Parasites;Pathway interactions;Patients;peripheral blood;Persons;Plasmodium;Plasmodium falciparum;polypeptide;Production;Productivity;Proliferating;Proteins;receptor;Regulation;Reporting;Research;Research Design;RNA analysis;Role;Salivary Glands;Sampling;Schools;Seasons;Sex Differentiation;Sexual Maturation;Site;Sporozoites;System;Temperature;Testing;Time;tool;Transcript;transcription factor;transcriptomic profiling;transmission blocking;transmission process;Up-Regulation;Variant

PROJECT_TITLE: Plasmodium falciparum gametocytogenesis in vitro and in vivo

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


ORG_CITY: KANSAS CITY

ORG_NAME: KANSAS CITY VA MEDICAL CENTER

PHR: Frailty is a multifactorial syndrome characterized by vulnerability to stressors that is intricately linked to cognitive impairment and mortality risk. Bright light therapy (BLT) reduces circadian disturbances by resynchronizing the hypothalamic biological clock via specific wavelengths of light. Human trials have demonstrated that BLT improves sleep quality and cognitive function in older adults. However, BLT has not been examined for use in older Veteran populations, particularly the impact on frailty. This randomized trial will assess the feasibility of employing BLT to study impacts on frailty, cognition, and sleep in older Veterans. Findings from this pilot will establish the power and effect size necessary for larger trials to support the use of BLT as readily available home-based treatment to improve healthspan of our Veterans.

PI_NAMEs: TROEN, BRUCE R. (contact)

PROJECT_TERMS: actigraphy;Affect;Age Years;aged;Aging;Amyloid beta-42;Amyloid beta-Protein;Area;Biological Clocks;Biological Markers;Brain;Chronic;Circadian Dysregulation;Circadian Rhythms;Clinical Trials;Cognition;Cognition Disorders;Cognitive;cognitive function;cognitive task;comorbidity;cost;Data Collection;diaries;disability risk;Drowsiness;Early Diagnosis;early onset;Enzyme-Linked Immunosorbent Assay;Exhibits;experience;Exposure to;Foundations;frailty;Goals;healthcare burden;healthspan;healthy aging;Home;Human;Hypothalamic structure;Impaired cognition;improved;improvement on sleep;interest;Intervention;Light;Link;Measurement;Measures;Medical;Melatonin;Mental Depression;mental state;military veteran;Minority;Modality;mortality risk;Motor;neurofilament;neurotropic;novel;older adult;Participant;Patient Recruitments;Phenotype;Phototherapy;Physical activity;Pittsburgh Sleep Quality Index;Predisposition;prevent;Prevention;Quality of Care;randomized trial;recruit;Research;resilience;Risk;Sampling;Seasonal Affective Disorder;Serum;Sleep;Sleep disturbances;sleep onset;sleep quality;Sleeplessness;stressor;Surveys;Syndrome;tau-1;Testing;Therapeutic;Time;Trail Making Test;treatment program;Universities;Veterans;Work

PROJECT_TITLE: Promoting cognitive resilience and reducing frailty in older Veterans with bright light therapy

STUDY_SECTION: RRDS

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Data Science;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Prevention;Women's Health Research

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PROJECT NARRATIVE Current interpretation of screening mammography suffers from human limitations, leading to approximately 30,000 missed cancers and 3.8 million false positives exams every year in the U.S. alone. Our multidisciplinary team of experts on breast cancer screening, machine and deep learning, data science, and imaging technology assessment will validate our highly accurate 2D mammography artificial intelligence (AI) algorithm that was the best performer in an international competition with >1,200 participants and then further enhance it with novel AI augmentation methods. We will then apply innovative techniques to scale the AI algorithm from 2D to 3D mammography, addressing the issue of a 50-to-100-fold increase in volumetric data with 3D exams, and then clinically translate our optimized AI 3D mammography tool through a series of interpretive accuracy studies involving experienced and inexperienced radiologists from both academic and community practices.

PI_NAMEs: LEE, CHRISTOPH I (contact)

PROGRAM_OFFICER_NAME: WU, YICONG

PROJECT_TERMS: 3-Dimensional;Address;algorithm development;algorithmic methodologies;Algorithms;Artificial Intelligence;artificial intelligence algorithm;Artificial Intelligence enhanced;artificial intelligence model;Benign;Big Data;Biometry;Biopsy;Black Box;Breast;Breast Cancer Detection;breast imaging;California;Characteristics;Clinical;clinical implementation;clinical risk;clinical translation;clinically relevant;clinically significant;cloud based;Code;Collaborations;Community Practice;computer aided detection;Computer software;Computers;crowdsourcing;Data;Data Science;Data Set;Data Storage and Retrieval;Databases;deep learning;Diagnosis;Diagnostic;digital;Digital Breast Tomosynthesis;Digital Mammography;DNA Sequence Alteration;Equilibrium;experience;genetic risk factor;Goals;Grant;Health;Human;Image;Imaging Device;Imaging technology;improved;industry partner;innovation;Institution;International;large-scale imaging data;Lead;Link;long short term memory;Machine Learning;Malignant Breast Neoplasm;Malignant Neoplasms;Mammographic screening;Mammography;Medicine;Metadata;Methods;Modality;Modeling;Molecular;molecular subtypes;mortality;multidisciplinary;Nature;novel;novel strategies;Oncology;Outcome;Output;Participant;Pathology;patient population;Performance;Population;population based;Positioning Attribute;prospective;Publications;radiologist;Radiology Specialty;Randomized, Controlled Trials;Registries;Reverse engineering;Risk;routine screening;screening;Seminal;Series;Supervision;Techniques;Technology Assessment;Testing;Time;tool;Training;Translating;tumor;Universities;Validation;Washington;Woman

PROJECT_TITLE: Artificial Intelligence for Improved Breast Cancer Screening Accuracy: External Validation, Refinement, and Clinical Translation


NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics

ORG_CITY: PORTLAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The mechanisms underlying virion assembly of adeno-associated virus (AAV) vectors in cells remain poorly understood, and there has been only limited progress in developing new methods to effectively produce AAV vectors at high titers. In this regard, the recent discovery of AAV assembly-activating protein (AAP) has opened a new avenue for AAV research. In this project, by comprehensively studying interactions between AAP, viral capsid protein and host cell proteins, we seek to elucidate the mechanism of virion assembly of AAV vectors in much greater depth, and explore novel strategies that can potentially improve AAV vector production.

PI_NAMEs: NAKAI, HIROYUKI  (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Address;adeno-associated viral vector;Bar Codes;Binding Proteins;Biology;Capsid;Capsid Proteins;Cell Nucleolus;Cells;Cellular biology;Clinical;cost effective;Coupled;Data;Dependovirus;Deubiquitinating Enzyme;Directed Molecular Evolution;Dose;Engineering;Exclusion;gene therapy;Gene Transduction Agent;Genes;Genome;Global Change;Heterogeneity;Human;improved;Individual;insight;interest;Knowledge;Label;manufacture;Masks;Mass Spectrum Analysis;Methods;Modeling;Molecular Biology;monomer;Mutagenesis;mutant;Nature;Nonstructural Protein;novel strategies;Outcome;overexpression;Pathway interactions;Patients;Play;Post-Translational Protein Processing;Process;Production;protein degradation;Protein Subunits;Protein-Protein Interaction Map;Proteins;Proteome;Proteomics;Research;Role;Series;Serotyping;Site;structural biology;Structure;Testing;Treatment Efficacy;ubiquitin isopeptidase;ubiquitin-protein ligase;Ubiquitination;vector;vector genome;Viral;Viral Proteins;Virion;Virus;Virus Assembly;virus host interaction

PROJECT_TITLE: Mechanistic Studies of AAP and Capsid Assembly of AAV Vectors

STUDY_SECTION: GDD

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


ORG_CITY: JACKSON

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MISSISSIPPI MED CTR

ORG_STATE: MS

PHR: PROJECT NARRATIVE Autoimmune diseases such as systemic lupus erythematosus (SLE) collectively impact approximately 24 million Americans, and cardiovascular disease is one of the leading causes of morbidity and mortality in this patient population. While subclinical vascular abnormalities such as endothelial dysfunction are prevalent in patients with SLE, the initiating factors that lead to the development of vascular disease remain poorly understood. This project focuses on the role of immune system dysfunction and gut dysbiosis, as well as their interaction, in the pathogenesis of vascular dysfunction in SLE.

PI_NAMEs: TAYLOR, ERIN BASSFORD (contact)

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: Academia;Age;American;arterial stiffness;Autoantibodies;Autoimmune Diseases;Autoimmunity;Bacteria;Biological Response Modifiers;Biophysics;Blood Vessels;Cardiovascular Diseases;career;Chronic Disease;Clinical Research;clinically relevant;comparison control;cytokine;Development;Educational process of instructing;Endothelial Cells;endothelial dysfunction;Endothelium;Female;Functional disorder;Goals;gut dysbiosis;gut microbiome;Hypertension;Immune system;Immune System Diseases;Impairment;improved;Institution;Interleukin-10;Laboratories;Lesion;Link;Mediating;Medical center;Mentors;microbiome analysis;microbiome composition;microbiota composition;Mississippi;Modeling;monocyte;Morbidity - disease rate;mortality;Mus;NZW Mouse;oral communication;Organ;Pathogenesis;pathogenic autoantibodies;patient population;Patients;Peptide Initiation Factors;Phase;Physiological;Physiology;premature;Productivity;Regulatory T-Lymphocyte;Relaxation;Research;Risk;Role;Scientist;Signal Transduction;skills;systemic autoimmune disease;Systemic Lupus Erythematosus;Techniques;Testing;tissue injury;Training;Training Activity;Transforming Growth Factor beta;Universities;vascular abnormality;Vascular Diseases;Work;Writing

PROJECT_TITLE: Immune system dysfunction and gut dysbiosis in the pathogenesis of vascular dysfunction in autoimmunity

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Pediatric;Pediatric Cardiomyopathy;Prevention;Rare Diseases

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Cardiac arrhythmias can lead to sudden death in seemingly healthy patients who carry specific mutations affecting proteins of the heart. I propose a state-of-the-art multi-level approach to elucidate the mechanisms of arrhythmia in a model of plakophilin-2 (PKP2) deficiency, which resembles the human disease arrhythmogenic right ventricular cardiomyopathy (ARVC). This research is relevant to public health because it aims to identify potential therapeutic targets to prevent arrhythmia and increase the life expectancy of patients with ARVC.

PI_NAMEs: ALVARADO, FRANCISCO J (contact)

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Ablation;Affect;Animals;Arrhythmia;Arrhythmogenic Right Ventricular Dysplasia;Biochemical;Calcium;Cardiac Myocytes;Cardiomyopathies;Cells;Cessation of life;Complex;Crossbreeding;Cyclic AMP-Dependent Protein Kinases;Cytosol;Data;defined contribution;Desmosomes;Disease;disease phenotype;Disease Progression;Dislocations;Drug Targeting;efficacy testing;Electrophysiology (science);Event;Exhibits;Functional disorder;Genes;Genetic;Goals;Heart;Heart Diseases;Heart failure;Hereditary Disease;Homeostasis;Human;human disease;Hyperactivity;Image;imaging study;Incidence;Infiltration;innovation;insight;Intercalated disc;Intercellular Junctions;Life Expectancy;Modeling;Molecular;Monitor;Mus;Mutation;Myocardial dysfunction;novel;Patients;Pharmaceutical Preparations;pharmacologic;Phase;Phenotype;Phosphorylation;Phosphorylation Site;Physiological;plakophilin 2;Post-Translational Protein Processing;Predisposition;prevent;Prevention;Protein Kinase C;Proteins;Public Health;receptor function;Regulation;Reporting;Research;Right ventricular structure;Risk Reduction;Role;Ryanodine Receptor Calcium Release Channel;Sarcoplasmic Reticulum;Site;sudden cardiac death;Sudden Death;Tamoxifen;Testing;therapeutic target;Threonine;Ventricular;Ventricular Arrhythmia

PROJECT_TITLE: Mechanisms of calcium-induced arrhythmias in arrhythmogenic right ventricular cardiomyopathy

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Chronic Pain;Clinical Research;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Pain Research;Pediatric;Temporomandibular Muscle/Joint Disorder (TMJD)

ORG_CITY: CLEMSON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: CLEMSON UNIVERSITY

ORG_STATE: SC

PHR: Project Narrative Human skeletal deformities involving the jaw affect ~6% of all adults and are often associated with pain and poor function of the two temporomandibular joints (TMJ) that allow for movement of the lower jaw during talking and eating. Surgery to correct these jaw skeletal deformities, and thus obtain better oral function, is often helpful but can cause problems for the TMJ. This project will determine the biomechanical and biologic conditions of the TMJ for patients with jaw skeletal deformities, both before and after surgery, to understand how these surgeries affect how well the TMJ works and thus aide surgeons to have better surgical outcomes.

PI_NAMEs: YAO, HAI  (contact)

PROGRAM_OFFICER_NAME: FISCHER, DENA

PROJECT_TERMS: 3-Dimensional;Adult;Affect;Biological;Biology;Biomechanics;Cell Survival;Clinical;clinical center;Complex;craniofacial;cranium;Data;Deformity;Dental Occlusion;Dependence;Deposition;Development;Eating;Elements;energy density;Energy Metabolism;Environment;Equilibrium;Etiology;Extramural Activities;Face;Female;Functional disorder;Future;Health;high risk;Human;improved;in vivo;Individual;insight;Jaw;joint biomechanics;joint function;joint loading;Joints;Knee;Literature;Mandible;Measurable;Measurement;mechanical energy;mechanical load;Mechanics;Methodology;Modeling;Morphology;Motion;Movement;Muscle;National Institute of Dental and Craniofacial Research;Nutrient;Nutrient availability;Operative Surgical Procedures;Oral;orthognathic;Outcome;Pain;Pathologic;Patients;Pattern;Phase;Phenotype;Prognathism;Publications;Reporting;Research Personnel;response;Retrognathism;Risk Factors;Sex Differences;sex disparity;sexual dimorphism;skeletal;Stress;Structure of articular disc of temporomandibular joint;Surgeon;surgery outcome;Temporomandibular Joint;Temporomandibular Joint Disorders;Temporomandibular Joint Dysfunction Syndrome;Tissues;United States National Institutes of Health;Work

PROJECT_TITLE: ATTRACT: Assessment of Temporomandibular JoinT MoRphology, Mechanics, And Mechanobiology in Class II and III Target and Surgical Phenotypes


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Pathologies ranging from neurodegeneration to chronic infection have in common the cytoplasmic accumulation of toxins including protein aggregates or whole invading microorganisms. Activation of macroautophagy drives the formation of a new organelle that functions to specifically sequester and eventually destroy these toxins. How this organelle forms, how it closes to complete sequestration and how it delivers its cargo for lysosomal destruction are the major long-term goals of this application.

PI_NAMEs: MELIA, THOMAS JAMES (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: 3-Dimensional;Architecture;Area;Autophagocytosis;Autophagosome;Binding;Biogenesis;biological adaptation to stress;Cell Line;Cells;Characteristics;chronic infection;Complement;Cytoplasm;Cytosol;Dedications;Electrons;Encapsulated;established cell line;Event;Excision;Exhibits;falls;Family;Family member;flexibility;Goals;Growth;Image;In Vitro;Individual;Invaded;Knock-out;lipid transfer protein;Lipids;Lumen of the Lysosome;Lysosomes;Mediating;Membrane;membrane reconstitution;microorganism;Morphology;Nerve Degeneration;Nutrient;Organelles;pathogen;Pathology;Pathway interactions;Peptide Hydrolases;Phase;Phosphatidylethanolamine;Phosphorylation;Phosphoserine;Physiologic pulse;Play;Process;progenitor;protein aggregation;protein expression;Protein Family;Proteins;reconstitution;recruit;Recycling;Regulation;Resistance;response;Role;Site;Source;Starvation;stressor;Structure;System;Technology;Tomogram;Toxin;Ubiquitin Like Proteins;ultra high resolution;unilamellar vesicle;Vesicle;Yeasts

PROJECT_TITLE: Regulation of Autophagosome Membrane Dynamics by the Atg8 Family of Proteins

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative The pentameric ligand-gated ion channels (pLGIC) mediate fast synaptic transmission in the central and peripheral nervous systems, and thereby critically govern numerous cellular processes such as pain perception, motor coordination, and gastrointestinal functions. Dysfunctions in pLGIC are associated with several psychiatric, neurological, and gastrointestinal disorders, and therefore these channels are important drug targets. The goal of the proposed studies is to elucidate fundamental mechanisms governing channel function and modulation at a molecular level. Findings from this work will lead to a better understanding of the role of pLGIC in various physiological and pathophysiological processes, and hence aid strategies for development of new and safer therapeutics.

PI_NAMEs: CHAKRAPANI, SUDHA  (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: addiction;Binding;Binding Proteins;Biochemical;Cell Physiology;Central Nervous System;chronic pain;Complex;Cryoelectron Microscopy;design;Development;Drug Targeting;Electrophysiology (science);Environment;Event;Functional disorder;Gastrointestinal Diseases;gastrointestinal function;Glycine Receptors;Goals;HTR3A gene;Ion Channel Gating;Knowledge;Length;Ligands;Lipids;Malignant Neoplasms;Mediating;Membrane;Membrane Lipids;Mental disorders;Molecular;Molecular Conformation;Mood Disorders;Motor;multidisciplinary;Nervous System Disorder;novel therapeutics;Pain;pain perception;particle;Peripheral Nervous System;Physiologic pulse;Physiological;Physiological Processes;Process;Protein Dynamics;receptor;Resolution;Rest;Role;Serotonin;serotonin receptor;Signal Transduction;Structure;Synaptic Transmission;Techniques;Therapeutic;Therapeutic Agents;therapeutic target;Therapeutic Uses;transmission process;Work

PROJECT_TITLE: Structure and Function of Pentameric Ligand-Gated Ion Channels

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Narrative Sebaceous glands secrete oils that are thought to be critical for healthy skin. This proposal seeks to identify factors that modulate sebaceous gland stem cells, and to test the requirement for these glands in maintaining proper skin function. Findings from these studies are relevant to normal skin biology, as well as to pathologies such as seborrheic dermatitis, acne and scarring alopecia.

PI_NAMEs: WONG, SUNNY Y (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: 16S ribosomal RNA sequencing;Ablation;Acne;Adult;Alopecia;anti-microbial drug;antimicrobial;Antioxidants;appendage;Attenuated;Biology;Candidate Disease Gene;Cell Compartmentation;Cells;Cicatrix;Communication;Complex;Cues;cytokine;Cytometry;Data Set;Defect;Disease;Dry Eye Syndromes;Epidermal Growth Factor Receptor;Epidermis;epigen;Epithelium;experimental study;Eye diseases;Eyelid structure;Foundations;Genes;Gland;Goals;Growth Factor;Hair;Hair follicle structure;Homeostasis;Hormones;Hydration status;Immune;keratin 5;Ligands;Link;lipidomics;Lipids;meibomian gland;microbiome research;Morphology;Mus;mutant;notch protein;novel;Oils;Outcome;Pathology;Pathway interactions;Play;Population;PPAR gamma;progenitor;Proliferating;Property;receptor;Regulation;Role;Sebaceous Glands;Seborrheic dermatitis;Sebum;Signal Pathway;Signal Transduction;Skin;skin barrier;skin disorder;Source;stem cell differentiation;stem cells;Surface;System;Testing;Time;transcription factor;transcriptome sequencing;Up-Regulation;Water;Work

PROJECT_TITLE: Functional characterization of sebaceous gland stem cells and sebocytes in the skin


ORG_CITY: Columbus

ORG_DEPT: CHEMISTRY

ORG_NAME: OHIO STATE UNIVERSITY

PHR: Project Narrative  The proposed research will provide powerful tools for the synthesis of pharmaceutically relevant compounds and their congeners from readily available alkenes, 1,3-dienes, enynes, and alkynes. Since highly catalytic reactions and readily available precursors are involved in the proposed new processes, successful conclusion of this project will also add to our repertoire of benign synthetic methods useful for large scale manufacture of useful pharmaceutical intermediates. This effort, if successful, will deliver tangible economic and environmental benefits; we hope that the discoveries made will shorten the considerable distance between the conceptualization of a molecule as a drug candidate and its large-scale synthesis.

PI_NAMEs: RAJANBABU, T V (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Highly Selective Catalytic Reactions of Alkenes and Alkynes Relevant to Medicinal and Process Chemistry

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


ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Apicobasal cell polarity is a unique process that generates an extraordinary diversity of epithelia through regulation of cell- cell junctions and the cytoskeleton. How polarity proteins direct spatial organization of different types of cell-cell junctions is a general subject of this proposal. It will uncover the role and mechanisms that are based on polarity proteins of Scrib and Par3 families in organization of two junctional structures Adherens Junctions and Desmosomes. The role of plakophilin family proteins, Pkp2, Pkp3, and Pkp4, in these processes is also under investigation. The study is a critical step toward the development of synthetic modulators of cell-cell adhesion and their application in medicine.

PI_NAMEs: TROYANOVSKY, SERGEY M (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Actins;Address;Adherens Junction;Adhesions;Adhesives;alpha catenin;antagonist;Apical;Architecture;Autoimmune Diseases;basolateral membrane;Binding;Biology;Cadherins;cell assembly;Cell membrane;Cell Polarity;cell type;Cell-Cell Adhesion;Cells;cohesion;Communication;Compensation;Complex;Cytoskeleton;Data;Defect;Desmosomes;Development;Disease;Dissection;Enzymes;Epithelial Cells;Epithelium;Evolution;extracellular;Family;Genetic Diseases;Goals;Grant;Guanine Nucleotide Exchange Factors;Inflammatory;Integral Membrane Protein;Intercellular Junctions;Invertebrates;Investigation;Lateral;Link;link protein;Location;Mammalian Cell;Mammals;Mediating;Medicine;Membrane;Minor;Modification;Molecular;Names;Pathway interactions;Phosphoric Monoester Hydrolases;plakophilins;Positioning Attribute;Process;Property;protease-activated receptor 3;Protein Family;Proteins;Publishing;Reagent;receptor;Regulation;rho;Role;Rosaniline Dyes;Signal Pathway;Signal Transduction;Simple Epithelium;Site;spatiotemporal;Structure;System;targeted treatment;Tight Junctions;Tissues;Work

PROJECT_TITLE: Intercellular junctions and cell polarity

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-H(80)S]


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

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disease with no effective treatment. Based on studies indicating a strong link between the insulin-like growth factor (IGF) system and AD, we propose to generate an AD mouse model lacking a unique enzyme that regulates local IGF action (PAPP-A). We hypothesize that deletion of PAPP-A protects against AD-like pathology and cognitive impairment, and, if so proven, would support the development of novel therapies for AD based on targeted inhibition of PAPP-A.

PI_NAMEs: CONOVER, CHERYL A. (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: Acceleration;Age;Age Months;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease therapy;Amyloid beta-Protein;amyloid formation;Astrocytes;Behavior;behavior test;Behavioral;Brain;Brain Pathology;cognitive change;cognitive function;Data;Deposition;Development;Disease;Early Onset Alzheimer Disease;effective therapy;Emotional;Enzymes;extracellular vesicles;Family;Friends;Gene Deletion;Genetic;Genotype;Heterozygote;Impaired cognition;Insulin-Like Growth-Factor-Binding Proteins;Insulin-Like-Growth Factor I Receptor;knock-down;Knock-out;Knockout Mice;Link;Mediator;Memory Loss;Microglia;mouse model;Mus;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Neurons;new therapeutic target;novel;novel therapeutics;object recognition;Oligopeptides;Pathologic;Patients;Peptide Hydrolases;Pregnancy-Associated Plasma Protein-A;prevent;Psyche structure;Receptor Activation;Receptor Mediated Signal Transduction;Research;Role;Senile Plaques;Signal Transduction;Somatomedins;System;Transgenes;Transgenic Mice

PROJECT_TITLE: PAPP-A as a Potential Target in Alzheimer's Disease

STUDY_SECTION: CDIN

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


NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: Narrative: The propose will examine the roles of a new pro-inflammatory molecule lysophosphatidylinositol (lysoPI) in endothelium activation, which would lead to the development of new therapeutics for cardiovascular diseases and stroke.

PI_NAMEs: YANG, XIAOFENG  (contact)

PROGRAM_OFFICER_NAME: PLAYFORD, MARTIN P

PROJECT_TERMS: Anti-Inflammatory Agents;Aorta;Apolipoprotein E;Arginine;atherogenesis;Atherosclerosis;Binding;Blood Vessels;Cardiovascular Diseases;CASP1 gene;Cell Adhesion Molecules;Cells;checkpoint receptors;CTLA4 gene;Data;Data Reporting;Development;Diabetes Mellitus;Endothelial Cells;Endothelium;Epigenetic Process;feeding;FOXP3 gene;Functional disorder;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Gene Activation;Generations;Genes;Goals;High Fat Diet;Human;Hyperlipidemia;immune checkpoint;Inflammasome;Inflammation;Inflammatory;Intercellular adhesion molecule 1;intercellular cell adhesion molecule;knock-down;Knockout Mice;Lesion;Lysophosphatidylcholines;lysophosphatidylinositol;Lysophospholipids;Macrophage;Mediating;metabolomics;Methyltransferase;Mitochondria;Modeling;Molecular;monocyte;Morbidity - disease rate;mortality;Mus;Myocardial Infarction;novel;novel therapeutics;oxidized low density lipoprotein;Paper;Pathway interactions;Pattern;Peripheral arterial disease;Phenotype;Plasma;Proteins;Publications;Publishing;Reactive Oxygen Species;receptor;receptor binding;recruit;Regulatory T-Lymphocyte;Reporting;Research;response;Risk Factors;Role;Signal Transduction;Stimulus;Stroke;Testing;Therapeutic Studies;TNF gene;Toll-like receptors;Transcription Factor AP-1;transcriptome sequencing;transcriptomics;Transferase;Transgenic Mice;Up-Regulation;vascular inflammation

PROJECT_TITLE: LysoPI/GPR55 pathway promotes endothelial activation, vascular inflammation and atherosclerosis

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Clinical Research;Duchenne/ Becker Muscular Dystrophy;Genetics;Heart Disease;Muscular Dystrophy;Orphan Drug;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: PROJECT NARRATIVE Heart failure is a leading cause of morbidity and mortality in certain forms of muscular dystrophy. Novel drugs are in development or have been approved for muscular dystrophy, but the effect on the heart is unclear. Through this work, we will develop platforms for testing drugs in human cells to evaluate the cardiac effectiveness of novel therapeutics for muscular dystrophy.

PI_NAMEs: FULLENKAMP, DOMINIC EDWARD (contact)

PROJECT_TERMS: 3-Dimensional;Affect;Annexin A6;Arrhythmia;Award;bench to bedside;Biological Markers;Biology;Biomedical Engineering;Cardiac;Cardiac Myocytes;cardiac tissue engineering;Cardiology;Cardiomyopathies;Cardiovascular system;career development;Cell Line;Cell membrane;Cell Nucleus;Cells;Clinical;clinical translation;clinically relevant;Code;Collaborations;comparison control;Complex;CRISPR/Cas technology;Data;Defect;Development;Development Plans;Dilated Cardiomyopathy;Disease;Doctor of Philosophy;drug testing;Duchenne muscular dystrophy;Dystrophin;Effectiveness;electrical measurement;Electrophysiology (science);Engineering;Ensure;exon skipping;experience;Extracellular Matrix;flexibility;flexible electronics;gene therapy;Genes;Genetic;Genetic Diseases;Genetic Medicine;Heart;Heart failure;Human;Hydrogels;improved;individualized medicine;induced pluripotent stem cell;induced pluripotent stem cell derived cardiomyocytes;inhibitor;Injury;interest;Intermediate Filaments;Lamin Type A;Lead;Left Ventricular Dysfunction;Life;Link;male;Measurement;Measures;Mechanical Stress;Mechanics;Membrane;Mentors;Mentorship;Methods;Modeling;monolayer;Morbidity - disease rate;mortality;Muscular Dystrophies;mutant;Mutation;Myocardium;novel;novel therapeutic intervention;novel therapeutics;Nuclear Envelope;Nuclear Lamina;Output;Pathologic;patient derived induced pluripotent stem cells;Patients;Phenotype;Physicians;Physiological;Play;Predisposition;protein complex;Proteins;prototype;Recombinants;Research;Research Personnel;response;Role;Sarcomeres;Scientist;Signal Transduction;Signaling Protein;Skeletal Muscle;Stress;stressor;Structural Protein;System;Technology;Testing;Therapeutic Effect;therapeutic evaluation;Tissue constructs;tissue culture;Tissues;Training;transmission process;Troponin;two-dimensional;Universities;Work

PROJECT_TITLE: Physiologic stress in advanced tissue culture models of cardiomyopathy

STUDY_SECTION: MCBS

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Chronic Pain;Mental Health;Neurosciences;Pain Research;Post-Traumatic Stress Disorder (PTSD);Prevention;Women's Health Research

ORG_CITY: BOSTON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: Project Narrative Sex differences in the development and prevalence of mental illnesses are widespread, suggesting that the risk factors that promote disease susceptibility may be distinct in men and women. This project explores the neurobiological basis of divergent fear responses in males and females, which could help identify novel ways to prevent or treat post-traumatic stress disorder.

PI_NAMEs: SHANSKY, REBECCA M (contact)

PROGRAM_OFFICER_NAME: VICENTIC, ALEKSANDRA

PROJECT_TERMS: Address;Animal Experimentation;Animals;Anterior;Auditory;Automobile Driving;awake;Behavior;Behavioral;behavioral outcome;behavioral response;Biological Assay;cell type;Cells;cingulate cortex;Clinical;conditioned fear;Conditioned Reflex;Conditioned Stimulus;Data;designer receptors exclusively activated by designer drugs;Development;Disease;Disease Marker;Disease susceptibility;disorder risk;experience;experimental study;Exposure to;Female;Fiber;foot;FOS gene;Freezing;Fright;Genetic Techniques;Goals;Immunohistochemistry;Individual;Individual Differences;insight;Investigation;Label;Lateral;Learning;Link;male;Maps;Measures;Mediating;Mediator;men;Mental disorders;Methodology;midbrain central gray substance;Modeling;neglect;neural;Neuroanatomy;neurobiological mechanism;Neurobiology;Neurons;novel;Outcome;Outcome Measure;Pain;pain model;pain processing;Phenotype;Photometry;Play;Post-Traumatic Stress Disorders;postsynaptic;pre-clinical;predict clinical outcome;predictive marker;Prefrontal Cortex;presynaptic;Prevalence;prevent;Proxy;Rattus;Reporting;resilience;response;Risk Factors;Rodent;Role;sensory integration;sensory stimulus;sex;Sex Bias;Sex Differences;sexual dimorphism;Shock;Stimulus;Stress;stress resilience;Stressful Event;Synapses;Testing;Time;Tracer;translational goal;translational neuroscience;Trauma;trauma exposure;traumatic event;Viral;Withdrawal;Woman;Women's prevalence

PROJECT_TITLE: Sex-dependent pain processing circuitry in classical Pavlovian fear conditioning

STUDY_SECTION: LMDN

STUDY_SECTION_NAME: Learning, Memory and Decision Neuroscience Study Section[LMDN]


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

ORG_CITY: RIVERSIDE

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

ORG_STATE: CA

PHR: Project Narrative It is estimated one third of human populations are chronically infected with the human pathogen, Toxoplasma gondii. Chronic toxoplasmosis cannot be prevented as there is no current treatment that eliminates the dormant tissue cyst in infected individuals. In this proposal, we will use a new innovative ex vivo model of tissue cyst reactivation to define the cellular and molecular basis of chronic disease, and thereby, open new avenues of research into new treatments that can prevent and cure chronic toxoplasmosis.

PI_NAMEs: WHITE, MICHAEL W;WILSON, EMMA H (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Acute;Amylopectin;Astrocytes;Auxins;Back;Biological;cell type;Cells;Chromatin;Chronic;Chronic Disease;chronic infection;Clinical;Competence;conditional knockout;Consumption;Cyclins;Cyst;Cytoplasmic Granules;Development;Developmental Process;Disease;Environment;Epigenetic Process;epigenome;experimental study;Face;Fibroblasts;Frequencies;Gene Expression;Genes;Genetic;genetic approach;Genetic Models;Glucose;Glycogen;Goals;Growth;Health;Hepatocyte;Human;human pathogen;Immunocompromised Host;In Vitro;Individual;innovation;Kinetics;Life;Life Cycle Stages;Metabolic;Metabolism;metabolomics;Methods;Mitochondria;Modeling;Molecular;Morphology;Mus;Muscle Fibers;Parasites;Parents;pathogen;Pathway interactions;Persons;Population;preservation;prevent;Proteins;Protocols documentation;Recombinants;Recrudescences;Research;Role;single cell sequencing;Sorting;Specificity;Sporozoites;Testing;Therapeutic;Tissue Expansion;Tissue Model;Tissues;Toxoplasma;Toxoplasma gondii;Toxoplasmosis;Transcription Process;transcriptome;transcriptome sequencing;Transgenic Organisms;Yeasts

PROJECT_TITLE: Defining the cell and molecular basis of Toxoplasma recrudescence

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Complementary and Integrative Health;Genetics;Mental Health;Neurosciences;Sleep Research

ORG_CITY: FARMINGTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

PHR: Narrative  This project is to investigate how melatonin regulates synaptic transmission and sleep through the BK channel, and how the BK channel is regulated by a newly identified molecular pathway. The results of this project will help our understanding about the molecular mechanisms of BK channel regulation and of melatonin’s sleep-promoting effects.

PI_NAMEs: WANG, ZHAO-WEN  (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: Action Potentials;Alcohol dependence;Amino Acids;Ataxia;Behavior;Behavioral;Binding;Biochemical;Biological;Biological Assay;Brain;Caenorhabditis elegans;CBA/CaJ Mouse;Cell Communication;Cell membrane;Cells;channel blockers;Chemical Agents;Chimera organism;Clathrin;Co-Immunoprecipitations;Complement;Disease;Dominant-Negative Mutation;Electrophysiology (science);Endocytosis;Epilepsy;experimental study;Fluorescence;forward genetics;Functional disorder;Gene Mutation;Genetic;genetic approach;genetic regulatory protein;Genetic Screening;Guanine Nucleotide Exchange Factors;Guanosine;Human;Hyperactivity;Immunohistochemistry;In Vitro;in vivo;insight;Intellectual functioning disability;knock-down;Knock-out;Knockout Mice;Knowledge;large-conductance calcium-activated potassium channels;Ligase;Ligation;loss of function;Lysine;Mass Spectrum Analysis;Mediating;Melatonin;Melatonin Receptors;Modeling;Molecular;Monomeric GTP-Binding Proteins;Mus;mutant;Mutate;Mutation;Nervous System;Nervous System Disorder;neural circuit;neuronal excitability;Neurons;neurotransmitter release;novel;Nucleotides;overexpression;Pathway interactions;paxilline;Phenotype;Physiologic pulse;Physiological;postsynaptic;Potassium Channel;presynaptic;Property;Proteins;Regulation;Ring Finger Domain;Role;Site;Sleep;sleep behavior;Slice;Source;suprachiasmatic nucleus;Surface;synaptic function;Synaptic Transmission;System;Testing;ubiquitin-protein ligase;Ubiquitination;Xenopus oocyte

PROJECT_TITLE: Synaptic function of BK channel-interacting proteins


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_CITY: LOS ANGELES

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative – Public Health Relevance  The proper coding of head movements by the inner ear vestibular epithelia depends upon communication between hair cells and afferent neurons through specialized subcellular structures known as synapses. The scientific tasks to be conducted through this project aim to develop critical methodologies required to investigate the structure-function relationship of individual synapses within the mammalian vestibular neuroepithelia. This work is critical to future studies designed to elucidate the alterations associated with many pathologic conditions and potential treatments targeting the pathologies to these critical sites.

PI_NAMEs: HOFFMAN, LARRY F (contact);SCHWEIZER, FELIX E

PROGRAM_OFFICER_NAME: CYR, JANET

PROJECT_TERMS: Acoustic Trauma;Affect;Afferent Neurons;Aging;analog;Architecture;Attenuated;Binding;Biosensor;Capsid;Characteristics;Cochlea;cochlear synaptopathy;Code;Communication;Complex;Coupled;Craniocerebral Trauma;Development;Dimensions;Disease;Dose;Encapsulated;Epithelium;Equilibrium;Etiology;Evaluation;Exhibits;experience;Experimental Models;experimental study;Face;Fluorescence;Foundations;Functional disorder;Future;Genotype;Glutamates;Hair Cells;Head Movements;Health;Heterogeneity;hidden hearing loss;high resolution imaging;Histologic;Immunohistochemistry;Individual;Investigation;Labyrinth;Light;Measures;Mediating;Membrane;method development;Methodology;Methods;Modification;Morphology;mosaic;mouse model;Mus;neurotransmitter release;Neurotransmitters;novel;Optics;OTOF gene;ototoxicity;Outcome;Pathologic;Pathology;Pattern;Peripheral;Phenotype;Physiological;postsynaptic;Postsynaptic Membrane;presynaptic;promoter;Proxy;public health relevance;Recovery;Reflex action;Reporter;Research;Research Design;response;ribbon synapse;Saccades;segregation;sensor;Signal Transduction;Site;Space Flight;Structure;Structure-Activity Relationship;Subcellular structure;superresolution microscopy;Synapses;Synapsins;synaptic function;Synaptic Receptors;temporal measurement;Testing;Time;tool;Transfection;Tubulin;Type I Hair Cell;Vestibular dysfunction;Vestibular epithelia;Vestibular function;Vestibular Hair Cells;Vestibular inner ear;vestibular system;Viral;Work

PROJECT_TITLE: Shedding light on balance: Interrogating individual synapses within vestibular epithelia

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: Veterans with comorbid chronic pain and depression are highly prevalent, have poor functional status and low quality of life, are at increased risk of suicide and lack access to effective treatments. To address this problem, the proposed research will examine the feasibility of a novel approach that integrates repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy with the overall goal of maximizing functional improvement in Veterans with chronic pain and depression. This is an important first-step in preparation for a future randomized efficacy trial. We will also include two cognitive control tasks with concurrent electroencephalography to explore as a potential objective indicator of treatment response. This application addresses a critical need within the Veterans Health Administration and is closely aligned with the focus area of developing suicide prevention treatments that influence participation in life roles.

PI_NAMEs: HERBERT, MATTHEW  (contact)

PROJECT_TERMS: Address;Adherence;Adverse event;Affect;Affective;Area;Attention;Blindness;bodily sensation;Brain;brain dysfunction;Brain region;chronic depression;chronic pain;chronic pain management;chronic pain patient;Clinical;Clinical Trials;cognitive control;cognitive function;comorbid depression;comorbidity;Data;Dropout;effective therapy;efficacy trial;Electroencephalography;emotion regulation;Emotional;Emotions;Enrollment;evidence base;expectation;experience;flexibility;Functional impairment;functional improvement;functional status;Future;Goals;Heart;improved;Individual;interest;Intervention;Left;Life;Literature;Living Wills;Measures;Mental Depression;Motivation;neuroimaging;Neurologic;noninvasive brain stimulation;novel;novel strategies;Outcome;Pain;Pain intensity;Pain interference;pain perception;pain reduction;Parietal;Participant;Pathway interactions;Personal Growth;Population;post intervention;Prefrontal Cortex;Preparation;Protocols documentation;psychologic;psychosocial;Quality of life;Questionnaires;Randomized;Randomized, Controlled Trials;reducing suicide;Regulation;Relative Risks;remediation;repetitive transcranial magnetic stimulation;Research;Role;satisfaction;Schedule;Severities;social engagement;social relationships;Spirituality;Stimulus;suicidal;suicidal risk;Suicide prevention;Therapeutic Intervention;Thinking;Treatment outcome;treatment response;Veterans;Veterans Health Administration;Visit;willingness;Work

PROJECT_TITLE: Integrated Repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy for Veterans with Chronic Pain and Depression


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

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Staphylococcus aureus, including methicillin-sensitive or -resistant varieties, is the major cause of skin/soft tissue infections and is being identified with greater frequency as the cause of more serious infections like endocarditis. Within the infection site, S. aureus can scavenge and use host-derived fatty acids to satisfy its lipid biosynthesis needs, but we do not yet understand the prevalence of these exogenous fatty acid in the S. aureus membrane or the impact they may have on antimicrobial therapies. In this project, we will determine the effects of host- derived fatty acids on the lipid composition, membrane physiology, and antibiotic tolerances of S. aureus with the goal of preventing treatment failures in internal organ and systemic infections.

PI_NAMEs: HINES, KELLY M. (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Accounting;Affect;Anti-Bacterial Agents;Anti-microbial susceptibility;anti-microbial tolerance;Antibiotic Resistance;Antibiotic susceptibility;antibiotic tolerance;Antibiotics;antimicrobial;Bacteria;Cardiolipins;Cellular Morphology;Cessation of life;Charge;Clinical;Communities;Community-Acquired Infections;Complex;Daptomycin;Data;efflux pump;Endocarditis;Environment;Failure;Fatty Acids;Frequencies;Genus staphylococcus;Goals;Growth;healthcare-associated infections;Heart;Hospitals;Human;Human body;In Vitro;in vivo;Infection;Infective endocarditis;Investigation;Isotope Labeling;Knowledge;Linoleic Acids;lipid biosynthesis;lipidomics;Lipids;Liquid Chromatography;liquid chromatography mass spectrometry;Liquid substance;Mass Spectrum Analysis;Measurement;Membrane;Membrane Fluidity;Membrane Lipids;Methicillin;methicillin resistant Staphylococcus aureus;methicillin susceptible Staphylococcus aureus;Methods;Microbial Biofilms;Monounsaturated Fatty Acids;Morphology;Multi-Drug Resistance;novel strategies;Nutrient;Oleic Acids;Organ;Outcome;Pathogenesis;Pathway interactions;Permeability;Phase;Phenotype;Phosphatidylglycerols;Phospholipids;Phosphotransferases;Physiological;Physiology;Polyunsaturated Fatty Acids;Predisposition;Prevalence;prevent;Prevention approach;Proteins;Reporting;Research;Resistance;Resolution;reversed phase chromatography;Role;Saturated Fatty Acids;Sepsis;Serum;Site;Skin;Soft Tissue Infections;Source;Stable Isotope Labeling;Staphylococcus aureus;Staphylococcus aureus infection;Structure;Supplementation;Surface;System;Systemic infection;Testing;Therapeutic;Time;Tissue Extracts;Tissues;Treatment Failure;Treatment Protocols;treatment risk;Unsaturated Fatty Acids

PROJECT_TITLE: Impacts of host lipid composition on antimicrobial susceptibilities of Staphylococcus aureus

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Women's Health Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: A dedicated breast PET-DBT scanner provides higher spatial resolution and sensitivity PET images compared to a clinical PET/CT scanner, that are co-registered to DBT images. The co-registered quantitative molecular and anatomical images can play an important role in breast cancer treatment - ranging from diagnostic breast imaging through surgical planning to systemic treatment.

PI_NAMEs: MAIDMENT, ANDREW DOUGLAS ARNOLD;SURTI, SULEMAN  (contact)

PROGRAM_OFFICER_NAME: DARDZINSKI, BERNARD JOSEPH

PROJECT_TERMS: 3-Dimensional;Adjuvant Chemotherapy;Air;Algorithms;anatomic imaging;Anatomy;Area;attenuation;Beds;Biological Markers;Biopsy;Biopsy Specimen;Breast;Breast biopsy;breast cancer diagnosis;Breast Cancer Early Detection;Breast Cancer Treatment;breast imaging;breast lesion;Breast Magnetic Resonance Imaging;cancer therapy;Clinical;clinical application;Clinical Research;cohort;Computer software;Core Biopsy;Data;data acquisition;Dedications;deep learning;design;detector;Development;Devices;Diagnostic;Digital Breast Tomosynthesis;Disease;efficacy testing;Estrogen receptor positive;Evaluation;fluorodeoxyglucose;Future;Geometry;Goals;Histopathology;Image;image reconstruction;imaging biomarker;imaging capabilities;imaging modality;Imaging Phantoms;improved;Intervention;Joints;Magnetic Resonance Imaging;Malignant Breast Neoplasm;Malignant Neoplasms;Measurement;Measures;Methodology;Methods;Modeling;Molecular;molecular imaging;molecular marker;Monitor;Morphologic artifacts;Motion;Neoadjuvant Therapy;next generation;novel;Operative Surgical Procedures;Patients;Performance;PET/CT scan;Phenotype;Pilot Projects;Play;Positioning Attribute;Positron-Emission Tomography;Primary Neoplasm;prospective;quantitative imaging;Radiation therapy;reconstruction;Residual Neoplasm;Resolution;response;Roentgen Rays;Role;Selection for Treatments;Source;Surgical Pathology;Survival Rate;System;Systemic Therapy;Techniques;Testing;Time;Tissue Sample;Tissues;tomosynthesis;tool;treatment response;Tube;tumor;ultra high resolution;uptake;Work;X-Ray Medical Imaging

PROJECT_TITLE: High Performance, Quantitative Breast PET Scanner Integrated With Tomosynthesis

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


NIH_SPENDING_CATS: Biotechnology;Chronic Obstructive Pulmonary Disease;Clinical Research;Genetics;Human Genome;Lung;Precision Medicine;Prevention;Pulmonary Fibrosis;Rare Diseases

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are two devastating chronic lung diseases with distinct clinical features, which may be due to genetic differences. In fact, there are at least five regions of the genome (loci) where the genetic variants that increase the risk of developing COPD decrease the risk of developing IPF. We plan to characterize how these “COPD/IPF opposite risk loci” contribute to gene expression changes in specific lung cells, which will give us new knowledge about the biology of COPD and IPF, both of which are lacking effective therapies.

PI_NAMEs: CHO, MICHAEL H. (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: Address;Affect;Aging;airway obstruction;Alleles;Alveolus;Architecture;ATAC-seq;Biological;Biological Process;Biology;causal variant;Cell Nucleus;Cell Physiology;cell type;Cells;Chronic lung disease;Chronic Obstructive Pulmonary Disease;cigarette smoking;Clinical;CRISPR interference;CRISPR-mediated transcriptional activation;Data;Data Set;Development;Disease;disorder risk;effective therapy;Environmental Risk Factor;Fibrosis;G-Protein-Coupled Receptors;Gene Expression;gene regulatory network;Genes;Genetic;genetic association;Genetic Risk;Genetic Transcription;genetic variant;Genome;genome editing;genome sequencing;genome wide association study;genomic locus;Genomics;Goals;idiopathic pulmonary fibrosis;improved;Inflammatory;Investigation;Joints;Knowledge;Lung;Maps;MicroRNAs;miRNA expression profiling;Molecular;Mucous Membrane;Multiple Sclerosis;myelination;Neurons;novel therapeutics;Nucleic Acid Regulatory Sequences;Obstruction;Pathogenesis;Pathologic;Pathology;Pathway interactions;Pharmaceutical Preparations;Phenotype;Physiology;polarized cell;precision medicine;Predisposition;Pulmonary Fibrosis;Pulmonary Pathology;Quantitative Trait Loci;Regulation;Regulatory Element;Research;Respiratory Disease;Risk;risk variant;RNA;Series;Shunt Device;single nucleus RNA-sequencing;Statistical Methods;Structure of parenchyma of lung;T-Lymphocyte;Therapeutic;Tissue Sample;Tissues;Total Lung Capacity;Trans-Omics for Precision Medicine;Validation;whole genome

PROJECT_TITLE: Uncovering the genetically-driven differential susceptibility to chronic obstructive pulmonary disease and pulmonary fibrosis

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Depression;Genetics;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Precision Medicine;Serious Mental Illness

ORG_CITY: NEW YORK

ORG_DEPT: PSYCHIATRY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE  The proposed research is relevant to the public because treatment resistant depression (TRD) is increasing in prevalence and represents a significant national cost. Motivated by our recent findings of decreased levels of acetyl-L- carnitine (LAC) in TRD, we seek to understand the role of central and peripheral mitochondrial metabolism of LAC in the effects of TMS-related effects on resting state functional connectivity and clinical responses. This work will lead to development of new multidimensional models of brain-body metabolic crosstalk and development of new therapeutic strategies.

PI_NAMEs: NASCA, CARLA  (contact)

PROGRAM_OFFICER_NAME: ANKUDOWICH, ELIZABETH

PROJECT_TERMS: Acceleration;Affect;Age;Anterior;anti-depressive agents;Antibodies;Bioinformatics;Biological Assay;Brain;Carnitine O-Acetyltransferase;Cell Nucleus;Clinical;Clinical Course of Disease;clinical phenotype;Computational algorithm;cost;Data;depression model;depressive symptoms;Development;disability;Enzymes;Epigenetic Process;epigenetic regulation;Exhibits;exosome;fatty acid oxidation;Foundations;Funding;Gene Expression;Genes;Glutamates;Goals;High-dimensional Modeling;hippocampal pyramidal neuron;Histone Acetylation;histone acetyltransferase;in vivo;Individual;inhibitor;innovation;insight;interest;Left;Levocarnitine Acetyl;Link;liquid chromatography mass spectrometry;magnetic beads;Maps;Metabolic;metabolomics;metabotropic glutamate receptor 2;Methodology;Mitochondria;mitochondrial metabolism;Modeling;Molecular;molecular phenotype;Molecular Target;Monitor;multidisciplinary;Nature;Neuronal Plasticity;Neurons;novel;novel marker;novel strategies;novel therapeutic intervention;Pathway interactions;Patients;Peripheral;personalized medicine;Phenotype;Plasma;Polymers;Positioning Attribute;pre-clinical;Precipitation;precision medicine;preclinical study;predictive marker;predictive modeling;Prefrontal Cortex;Prevalence;Protocols documentation;Psychiatry;Randomized;receptor;Regulation;Remission Induction;Research;response;Rest;Rodent Model;Role;Severities;sex;Sex Differences;sexual dimorphism;Signal Pathway;Specificity;stem;Testing;Therapeutic;therapeutic target;Time;translational approach;treatment response;treatment-resistant depression;United States National Institutes of Health;Work

PROJECT_TITLE: A translational approach for novel mechanisms of epigenetic regulation in treatment responses: toward a precision medicine model

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


ORG_CITY: HERSHEY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: Project Narrative The heart pumps blood into the systemic system by contracting cardiac muscle during systole, which is initiated by a rise in intracellular calcium concentration that triggers sliding of the thick and thin filaments in the muscle sarcomere. Myosin is the molecular motor that uses the energy from ATP hydrolysis to drive filament sliding and mutations in myosin can lead to dilated cardiomyopathy, a common form of heart failure that disrupts systolic contraction. This proposal will investigate the impact of dilated cardiomyopathy mutations on several aspects of human beta-cardiac myosin structure and function, including the regulatory mechanism, structural mechanism of force generation, and ability to drive filament sliding in a calcium dependent manner.

PI_NAMEs: SIVARAMAKRISHNAN, SIVARAJ ;WARSHAW, DAVID M;YENGO, CHRISTOPHER M (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Actins;Adopted;arm;ATP Hydrolysis;ATP phosphohydrolase;beta-Myosin;Binding;Biochemical;Biomedical Engineering;Biophysics;Biosensor;blood pump;Calcium;Cardiac;Cardiac Myocytes;Cardiac Myosins;Closure by clamp;Computer Models;Contracts;Data;Defect;design;Dilated Cardiomyopathy;Disease;DNA;Electron Microscopy;Enzymatic Biochemistry;Equilibrium;Filament;Fluorescence Resonance Energy Transfer;Fluorescence Spectroscopy;Foundations;Generations;Genes;Genetic;Goals;Head;Heart;Heart failure;Human;human disease;Impairment;in silico;Individual;Inherited;Kinetics;Lasers;Left;Link;Measurement;Measures;mechanical properties;Mechanics;Microfilaments;Modeling;Molecular;Molecular Conformation;molecular mechanics;Molecular Motors;Molecular Structure;Monitor;Motor;motor impairment;Muscle;Muscle Cells;Muscle Contraction;Muscle Fibers;muscle physiology;mutant;Mutate;Mutation;Myocardium;Myosin ATPase;Nanotubes;Nonmuscle Myosin Type IIA;novel;optic trap;optical traps;Pathogenesis;Point Mutation;Power stroke;prevent;Property;recruit;Regulation;Relaxation;Reporting;Sarcomeres;sensor;single molecule;Slide;Striated Muscles;structural biology;Structure;System;Systole;Systolic Pressure;Tail;Testing;Therapeutic;therapy development;Thick Filament;Thin Filament;Ventricular

PROJECT_TITLE: Impact of dilated cardiomyopathy mutations on cardiac myosin structure and function

STUDY_SECTION: MSFC

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


ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PHR: Project Narrative Beta-adrenergic receptors (βARs) are key regulators of cardiac function. β-blockers are the first line of therapy, but however they only delay the progression of heart failure with a survival window of 5 years short of surgical intervention. Our studies will provide mechanistic insights on the potential for targeting a novel pathway that could hold significant translational promise for heart failure.

PI_NAMEs: PRASAD, SATHYAMANGLA V (contact)

PROJECT_TERMS: Acceleration;Acute;Address;Adrenergic beta-Antagonists;Adult;Amino Acids;aorta constriction;Belief;beta-adrenergic receptor;Binding;Biological Assay;Breeding;C-terminal;Cardiac;Cardiac Myocytes;Cell surface;Cells;Coupling;Cyclic AMP;Data;desensitization;Diagnosis;dimer;Dimerization;Docking;Dominant-Negative Mutation;Down-Regulation;Endocytosis;Endosomes;Epinephrine;flexibility;Functional disorder;G protein coupled receptor kinase;GTP-Binding Protein alpha Subunits, Gs;GTP-Binding Proteins;Heart failure;heart function;heart preservation;Homodimerization;Hormones;Human;Impairment;In Vitro;in vivo;insight;Isoproterenol;Knockout Mice;Knowledge;Measures;Mediating;mimetics;mouse model;Mus;Myocardial dysfunction;Nature;Norepinephrine;novel;Operative Surgical Procedures;Outcome;Pathway interactions;phosphatase inhibitor;Phosphatidylinositols;phosphoproteomics;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Physiology;preservation;Process;promoter;Protein Dephosphorylation;Protein phosphatase;protein purification;Proteomics;receptor function;Regulation;Role;SET gene;Stress;Testing;Therapeutic;tool;Transgenic Mice;Transgenic Organisms

PROJECT_TITLE: Novel regulation of beta-adrenergic receptor function by phosphoinositide 3-kinase

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Breast Cancer;Cancer;Clinical Research;Dementia;Genetics;Neurodegenerative;Neurosciences;Prevention;Rehabilitation;Women's Health Research

PHR: PROJECT NARRATIVE Dr. Peng proposes to comprehensively investigate breast cancer and its treatment (chemotherapy, radiation, and hormone therapy) with global and domain-specific cognitive trajectory over time and to characterize cancer hallmark pathways in brain tissues of Alzheimer’s disease (AD) patients and controls to identify intersecting mechanisms for cancer and AD to inform targeted intervention. This research, together with Dr. Peng’s proposed trainings in aging epidemiology, cancer survivorship, and advanced statistical modeling, will enable Dr. Peng to conduct interdisciplinary research to study the deep connections between cancer and aging and to identify interventions targeting common pathways of cancer and AD to prevent both diseases.

PI_NAMEs: PENG, CHENG  (contact)

PROGRAM_OFFICER_NAME: FRANKOWSKI, DAVID WITT

PROJECT_TERMS: ABCB1 gene;acute toxicity;Address;Adherence;Affect;Aftercare;age acceleration;Aging;aging brain;aging population;Alzheimer's Disease;Alzheimer's disease patient;anti-cancer research;Antineoplastic Agents;Area;Attenuated;blood-brain barrier crossing;Brain;brain tissue;breast cancer diagnosis;Breast Cancer survivor;Breast Cancer Treatment;cancer diagnosis;Cancer Etiology;Cancer Survivor;Cancer Survivorship;cancer therapy;Caring;chemobrain;chemotherapy;Clinical Research;Cognition;Cognitive;cognitive function;cognitive testing;Diagnosis;Diagnostic;Disease;Drug Transport;Elderly;Epidemiology;Etiology;experience;follow-up;Gene Expression;Genes;Genetic;genetic analysis;Genetic Polymorphism;Genomic Instability;Genomics;Germ Lines;Goals;good diet;Healthy Eating;Heritability;high risk;hormone receptor-negative;hormone therapy;Human;human old age (65+);Impaired cognition;improved;Incidence;indexing;Inflammation;Interdisciplinary Study;Intervention;Investigation;Joints;Life Style;Long-Term Effects;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Measures;Mediterranean Diet;Mitochondria;Molecular;molecular subtypes;Mutation;neural repair;Nurses' Health Study;Observational Study;oxidation;Oxidative Stress;Pathway interactions;Pharmaceutical Preparations;Physical activity;pluripotency;Population;Population Study;Positioning Attribute;prevent;Proliferating;prospective;Quality of life;quality of life for cancer survivors;Radiation;Radiation therapy;Recording of previous events;Regulation;Reporting;Research;Research Personnel;Resources;Risk;risk prediction;Role;skill acquisition;Statistical Models;Strategic vision;Subgroup;Survival Rate;Survivors;Tamoxifen;Time;Toxicity due to chemotherapy;TP53 gene;Training;trait;transcriptomics;Woman;women's diagnosis

PROJECT_TITLE: Living beyond cancer: the short- and long-term cognitive effects of breast cancer and its treatment for cancer survivors

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]