ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE The Indiana Clinical Translational Science Institute is a partnership among Indiana's three research-intensive universities, Indiana University, Purdue University, and the University of Notre Dame, and the Regenstrief Institute, and has a distinguished history of documented success and a robust statewide research, educational, and community infrastructure on which to build its expansion in this new CTSA funding period. We will transform our statewide research ecosystem with deliberate attention to diversity and inclusion and the principles of trustworthiness and community engagement in our partnerships, workforce development and research engagement. We will accelerate innovation and rapidly implement evidence into practice in order to advance health equity.

PI_NAMEs: MOE, SHARON M (contact);WIEHE, SARAH ELIZABETH

PROGRAM_OFFICER_NAME: NAGEL, JOAN DAVIS

PROJECT_TERMS: 3D Print;Abbreviations;Acceleration;Address;Attention;Award;biobank;care providers;catalyst;Clinical Data;clinical practice;Clinical Research;Clinical Sciences;clinical translation;Collaborations;Collection;Communication;Communities;community college;community engagement;community organizations;County;COVID-19;COVID-19 pandemic;COVID-19 vaccine;dashboard;Data Sources;Development;Disparate;distrust;diversity and inclusion;Ecosystem;Education;Elements;empowerment;Engineering;Environment;equity, diversity, and inclusion;Ethics;Evidence based intervention;Evidence based practice;Face;Family;Federally Qualified Health Center;Fostering;Foundations;Funding;Government;Government Agencies;Health;health care service organization;health disparity;health equity;Health Personnel;Health system;Healthcare;Healthcare Systems;Hospitals;Hour;Human;implementation strategy;improved;Indiana;Informatics;Infrastructure;innovation;Institution;Institutional Review Boards;International;Journals;Knowledge;marginalized population;medical schools;member;Mind;Mission;novel strategies;Outcome;pandemic disease;Participant;Patient Care;Patients;Peer Review;personal protective equipment;Play;policy recommendation;Population Heterogeneity;Process;programs;Public Health;Public Health Informatics;public trust;Publications;Recommendation;Recording of previous events;Research;research and development;Research Personnel;Resources;response;Role;Rural;Science;Scientist;Services;Social Work;success;System;Touch sensation;Training;Training and Education;Training Programs;Translational Research;Trust;trustworthiness;Underserved Population;Universities;vaccine trial;Workforce Development

PROJECT_TITLE: Indiana Clinical and Translational Sciences Institute


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: Cancer;Childhood Leukemia;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_FIPS: US

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

ORG_STATE: PA

PHR: Although tremendous progress has been made in treatment modalities of acule myelogenous leukemias (AMLs) and myeloproliferative neoplasms (MPNs), there is the necessity to improve and develop novel therapeutic approaches. We propose to develop a strategy based on gene mutation profiling to identify patients with AMLs and MPNs displaying specific defects in DNA damage repair pathways. These pathways will be then attacked by DNA repair inhibitors combined with already approved drugs in the conditions mimicking peripheral blood and bone marrow niche to eliminate quiescent and proliferating AML and MPN stem and progenitor cells without affecting normal cells and tissues.

PI_NAMEs: SKORSKI, TOMASZ  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Acute Myelocytic Leukemia;Affect;Blood;Bone Marrow;brca gene;cancer cell;cancer stem cell;Cell Death;Cell membrane;Cell Proliferation;Cells;chemotherapy;Cytoplasm;Data;Defect;Disease;Disease remission;DNA Damage;DNA Double Strand Break;DNA Repair;DNA Repair Disorder;DNA Repair Pathway;DNA-dependent protein kinase;DNMT3a;Double Strand Break Repair;driver mutation;Epigenetic Process;FLT3 gene;Foundations;Gene Mutation;Genes;Genetic;Genomic Instability;Hematopoietic Neoplasms;homologous recombination;Human;immunodeficiency;improved;inhibitor;JAK2 gene;leukemia;Leukemic Cell;leukemic stem cell;Malignant - descriptor;Malignant Neoplasms;Mediating;Modality;Modeling;Mus;Mutate;Mutation;Myeloid Leukemia;Myeloproliferative disease;news;Nonhomologous DNA End Joining;Normal Cell;Normal tissue morphology;novel therapeutic intervention;novel therapeutics;Oncogenic;Pathway interactions;Patient-Focused Outcomes;Patients;peripheral blood;Pharmaceutical Preparations;Play;Poly(ADP-ribose) Polymerase Inhibitor;prevent;Proliferating;protective effect;Protein Tyrosine Kinase;Refractory;repaired;Reporting;Research;Resistance;response;Role;Sampling;standard care;stem;Stem cell transplant;stem cells;Testing;Therapeutic;Therapeutic Effect;therapeutic evaluation;therapy outcome;tumor;tumor initiation;Tyrosine Kinase Inhibitor;Update;Work;Xenograft procedure

PROJECT_TITLE: Oncogenic tyrosine kinases inhibitors abrogate DNA repair and sensitive leukemias to PARP inhibitors

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


ADMINISTERING_IC: HL

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Cooley's Anemia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Prevention;Rare Diseases;Sickle Cell Disease

ORG_CITY: Portland

ORG_NAME: HEMEX HEALTH, INC.

ORG_STATE: OR

PHR: PROJECT NARRATIVE Anemia, sickle cell disease, and beta-thalassemia are blood disorders that affect millions of people in the United States and worldwide. There is no Food and Drug Administration-approved point-of-care diagnostic device for sickle cell or beta-thalassemia in the United States. In this project, we plan to complete US-centric analytical and clinical validation studies for FDA 510(k) applications and commercialize Gazelle in the US as the first and only integrated point-of-care diagnostic platform for sickle cell disease, beta-thalassemia, and anemia.

PI_NAMEs: GALEN, PETER  (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Adult;Affect;Africa;Africa South of the Sahara;African American population;American;Anemia;beta Thalassemia;Blood;Blood Tests;Blood Transfusion;Childhood;Clinical;commercialization;Country;Decision Making;Development;Devices;Diagnosis;Diagnostic;Diagnostic Equipment;diagnostic platform;Diagnostic tests;Disease;Early Diagnosis;early screening;FDA approved;Feedback;Fetal Hemoglobin;Gene Mutation;Genes;Goals;Hematological Disease;Hemoglobin;Hemoglobin concentration result;High Prevalence;Hispanic Populations;Howard Temin Award;hydroxyurea;India;Inherited;Intrauterine Blood Transfusion;Low income;Malnutrition;manufacture;Marketing;Measures;Methods;Microchip Electrophoresis;Middle Eastern;Modification;Monitor;Mutation;Patient Monitoring;Patients;Persons;Phase;point of care;point of care testing;point-of-care diagnostics;Population;Prevention;Provider;Reference Standards;Sales;Sampling;screening;Sickle Cell;Sickle Cell Anemia;Sickle Cell Trait;Sickle Hemoglobin;Small Business Innovation Research Grant;South Asian;Southeastern Asia;Testing;Thalassemia;trait;Transfusion;United States;United States Food and Drug Administration;Validation;validation studies;Variant

PROJECT_TITLE: Affordable, quantitative, point-of-care microchip-electrophoresis for screening and treatment monitoring of sickle cell disease, thalassemias, and anemias


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: STANFORD

ORG_DEPT: BIOLOGY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: OVERALL NARRATIVE The Cyclin D-Cdk4/6-Rb-E2F pathway normally integrates external and internal signals to control cell cycle progression at the G1/S transition of the cell cycle. Alterations in the Cyclin D-Cdk4/6-Rb-E2F pathway are found in the vast majority of human cancers. These alterations are thought to increase the proliferative potential of cancer cells. Here we propose an in-depth mechanistic investigation of all levels of the Cyclin D-Cdk4/6-Rb-E2F pathway to gain novel insights into fundamental aspects of the mechanisms of action of this pathway in cells, with the hope that these studies will reveal novel ways to block the proliferation of cancer cells in patients.

PI_NAMEs: RUBIN, SETH MICHAEL;SKOTHEIM, JAN M (contact)

PROGRAM_OFFICER_NAME: GHOSH-JANJIGIAN, SHARMISTHA

PROJECT_TERMS: Automobile Driving;Binding;Binding Sites;Breast Cancer Treatment;cancer cell;Cancer Control;cancer genetics;Cancer Patient;cancer therapy;cancer type;CCNE1 gene;Cell Cycle;Cell Cycle Kinetics;Cell Cycle Progression;Cell Cycle Regulation;Cell division;cell growth;cell preparation;Cell Proliferation;Cells;Cellular biology;Clinic;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Consensus;Cyclin D1;Cyclin-Dependent Kinases;design;Development;Dissociation;DNA;DNA biosynthesis;E2F transcription factors;Event;experimental study;Family member;G1 Phase;G1/S Transition;Genes;Genetic Transcription;genome editing;Goals;Human;imaging approach;improved;Inhibition of Cell Proliferation;inhibitor;innovation;insight;interdisciplinary approach;Investigation;kinase inhibitor;Knowledge;Malignant Neoplasms;Measures;Medicine;Modeling;Molecular;molecular imaging;Normal Cell;novel;novel strategies;novel therapeutic intervention;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Phosphorylation;Phosphotransferases;Post-Translational Protein Processing;Pre-Clinical Model;Program Research Project Grants;programs;Proliferating;protein protein interaction;Proteomics;Recurrence;Regulation;response;Retinoblastoma Protein;retinoblastoma tumor suppressor;S phase;Series;Signal Transduction;Structural Biochemistry;structural biology;success;Systems Biology;targeted treatment;Technology;Testing;Therapeutic;tumor;Tumor Suppressor Proteins;Work

PROJECT_TITLE: Determining and targeting mechanisms controlling cancer cell division


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: NEW YORK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: PROJECT NARRATIVE This project aims at investigating mechanisms underlying maladaptive immune responses in tauopathy models of Alzheimer's disease. This study may provide new therapeutic avenue for treating this devastating disease.

PI_NAMEs: GAN, LI  (contact)

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: Affect;Alleles;Alzheimer's Disease;Alzheimer's disease model;Anti-viral Response;Binding;Bone Marrow;Brain;Cell Nucleus;cell type;Cells;clinical heterogeneity;Cognitive deficits;cognitive function;Cyclic GMP;cytokine;Dementia;Diet;Disease;DNA;DNA Damage;DNA Repair Inhibition;Dose;ds-DNA;Electrophysiology (science);Exhibits;Family;Genes;Genetic;Genetic study;Goals;Hippocampus;Human Genetics;Hyperactivity;hyperphosphorylated tau;Image;imaging study;Immune;Immune response;Immunomodulators;Impairment;in vivo;Inflammation;Inflammatory Response;inhibitor;Innate Immune Response;Interferon Activation;Interferon Type I;Interferons;Intervention;Late Onset Alzheimer Disease;Learning;Link;Mediating;Memory impairment;Memory Loss;Microglia;Modeling;monocyte;mouse model;mRNA Expression;Mus;Neurofibrillary Tangles;Neurons;novel;novel therapeutic intervention;novel therapeutics;Nuclear;Outcome;Pathologic;Pathology;Pathway interactions;Permeability;pharmacokinetics and pharmacodynamics;pharmacologic;Phenocopy;Phosphorylation;Plasma;preclinical study;Preventive;Property;protective effect;Proteins;recruit;response;Risk;risk variant;Role;Senile Plaques;sensor;Signal Transduction;single nucleus RNA-sequencing;small molecule;Source;Stimulator of Interferon Genes;Synapses;TANK-binding kinase 1;tau mutation;tau Proteins;Tauopathies;Testing;Therapeutic;Toxic effect;transcription factor;transcriptome;transcriptomics;Viral

PROJECT_TITLE: Maladaptive antiviral pathways in Alzheimer's disease

STUDY_SECTION: CDIN

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


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Suicide prevention is VA’s highest clinical priority, and the greatest number of lives lost to suicide are in older Veterans. However, most national suicide prevention programs target younger military personnel and Veterans returning from combat. Thus, the on-going work by Dr. Amy Byers on suicide-risk detection and prevention in older Veterans is imperative. She is a leader in investigating salient risk factors related to late-life suicide using nationally based, large-scale data. Her work uses substantial creativity and originality to identify new and timely issues on which to conduct research projects and to extend existing knowledge in the areas of suicide, aging, and mental health. She has an active and vigorous research program that is capable of obtaining continued VA Merit Review funding, as well as extramural peer review funding. The Research Career Scientist Award will support Dr. Byers’ on-going research activities in these areas, advancing the current landscape of VA’s suicide prevention programs.

PI_NAMEs: BYERS, AMY LYNN (contact)

PROJECT_TERMS: adverse outcome;Age;Aging;Alzheimer's Disease;American;anti-depressive agents;anti-epileptic agents;Antipsychotic Agents;Anxiety Disorders;Area;Award;Benzodiazepines;Biometry;Biostatistical Methods;Capsicum;career;Cessation of life;Clinical;clinically relevant;cohort;Collaborations;combat;Communities;comorbidity;Complex;Connecticut;Creativeness;Cross-Over Studies;Data;Data Linkages;Data Set;Dementia;Detection;Diagnosis;diagnostic signature;Disease;dual diagnosis;Epidemiology;ethnic disparity;experience;Extramural Activities;Feeling suicidal;Female;Fostering;frailty;Funding;Future;geriatric depression;Gerontology;Grant;health disparity;health service use;Health Services Administration;Healthcare;high risk;Homelessness;hormone therapy;hypnotic;Imprisonment;Investigation;Journals;Knowledge;large-scale database;late life;Life Experience;Link;Manuscripts;Mental Depression;Mental disorders;Mental Health;Mental Health Services;Methodology;middle age;mild cognitive impairment;Military Personnel;military veteran;Minority;Modality;Mood Disorders;mortality;Names;National Institute of Mental Health;National Institute on Minority Health and Health Disparities;Nature;neuropsychiatry;novel;older adult;older women;Opioid;originality;Outcome;Overdose;Paper;parent grant;Pattern;Peer Review;Personal Satisfaction;Pharmaceutical Preparations;Polypharmacy;Positioning Attribute;Post-Traumatic Stress Disorders;Preparation;Prevention;Prevention program;Primary Care;Prisons;Probability Samples;Prognostic Factor;Program Development;programs;Psyche structure;Psychiatry;Psychotropic Drugs;Publishing;Qualifying;racial disparity;Recording of previous events;Reporting;Research;Research Activity;Research Design;Research Project Grants;Risk;Risk Factors;Scientist;sedative;Seminal;social;social stigma;Societies;suicidal behavior;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;Suicide prevention;System;Trauma;trauma exposure;United States Centers for Medicare and Medicaid Services;United States National Institutes of Health;Universities;Veterans;Veterans Health Administration;Vulnerable Populations;Work

PROJECT_TITLE: CSRD Research Career Scientist Award Application


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Fragile X Syndrome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: LOS ANGELES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: NARRATIVE: These studies will investigate deficits in sensory processing that negatively impact quality of life of individuals with Fragile X syndrome (FXS) and related autism spectrum disorders. We propose translational studies in mice and humans, with the goal of finding new treatments to alleviate sensory hypersensitivity and atypical sensory processing in affected individuals.

PI_NAMEs: ERICKSON, CRAIG ;PORTERA-CAILLIAU, CARLOS  (contact)

PROGRAM_OFFICER_NAME: LEE, CRYSTAL ANNE

PROJECT_TERMS: Address;Adult;Affect;Anxiety;area striata;Arousal;Attentional deficit;Auditory;autism spectrum disorder;awake;Behavioral;behavioral impairment;behavioral phenotyping;Biological;Brain;cell type;Cells;Characteristics;Clinic;Clinical Research;Clinical Trials;Collaborations;comparison control;Coupling;Cre-LoxP;Data;Defect;designer receptors exclusively activated by designer drugs;discrimination task;distraction;Down-Regulation;Electroencephalography;Epilepsy;Exhibits;Experimental Designs;experimental study;Fragile X Syndrome;Frequencies;Functional disorder;Future;Genes;Genetic;genetic approach;Goals;hippocampal pyramidal neuron;Human;human subject;Hypersensitivity;Imaging Techniques;Impairment;improved outcome;in vivo calcium imaging;in vivo imaging;Individual;Inherited;inhibitory neuron;innovation;insight;Intellectual functioning disability;Interneurons;Investigation;Knockout Mice;Knowledge;Laboratories;Lead;Learning;Link;Methodology;migration;Molecular;Morphology;mouse model;Mus;Nature;neural;Neurodevelopmental Disorder;Neurons;neuropathology;neuroregulation;Neurosciences;novel;novel strategies;Output;Paper;Participant;Parvalbumins;Pathogenesis;Pathway interactions;Performance;Phase;Population Dynamics;Publishing;Quality of life;Reporting;Research;Research Personnel;Reverse engineering;Role;Running;Sensory;sensory discrimination;sensory input;sex;Silicon;Stimulus;Symptoms;Synapses;Tactile;Task Performances;Techniques;Testing;Time;translational approach;translational study;Universities;Vasoactive Intestinal Peptide;Visual;visual discrimination;Visual impairment

PROJECT_TITLE: Circuit Disruptions Underlying Atypical Sensory Processing in Fragile X Syndrome

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Cystic Fibrosis;Emerging Infectious Diseases;Genetics;Infectious Diseases;Lung;Rare Diseases

ORG_CITY: ATLANTA

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

ORG_STATE: GA

PHR: Project Narrative Antimicrobial resistance (AMR) is a problem in many types of infectious disease, but one area of particular concern is in individuals with cystic fibrosis (CF) infected with Pseudomonas aeruginosa (Pa). This study will identify evolutionary mechanisms that drive AMR heterogeneity in Pa populations, and ascertain novel genomic loci that are involved in regulatory pathways that control in vivo AMR. The project will answer a number of unsolved questions that will advance understanding of AMR in the context of CF, and suggest improvements for antibiotic treatment and susceptibility testing in clinical labs.

PI_NAMEs: DIGGLE, STEPHEN PAUL (contact)

PROGRAM_OFFICER_NAME: GU, XIN-XING

PROJECT_TERMS: Acute;Affect;Age;Anti-microbial susceptibility;Antibiotic Resistance;Antibiotic susceptibility;Antibiotic Therapy;Antibiotics;Antimicrobial Resistance;Area;Bacteria;Bacterial Genome;beta-Lactamase;Biological Assay;Chronic;Clinic;Clinical;Communicable Diseases;Communities;computational platform;Confocal Microscopy;Correlation Studies;Cystic Fibrosis;cystic fibrosis infection;cystic fibrosis patients;de novo mutation;Development;diagnostic strategy;Diagnostic tests;Evolution;experience;experimental study;fitness;follow-up;Future;Genes;Genetic;Genetic Diseases;Genetic Heterogeneity;Genetic Recombination;genome analysis;genome wide association study;genomic biomarker;genomic locus;genomic signature;Goals;Growth;Heterogeneity;homologous recombination;improved;in vivo;Individual;insight;Life;Link;Lung;Lung Diseases;Lung infections;Methodology;Microbial Biofilms;microbial community;Modeling;mRNA Differential Displays;Mucins;Mutation;novel;novel diagnostics;opportunistic pathogen;Organism;Outcome;pathogenic bacteria;Patients;Phenotype;Phylogeny;Physiology;Population;Population Dynamics;Population Heterogeneity;predict clinical outcome;Privatization;Production;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Pulmonary Cystic Fibrosis;pulmonary function;reconstruction;Regulatory Pathway;Research;Resistance;resistance mechanism;resistant strain;Sampling;social;Social Interaction;Source;Sputum;Structure;Testing;Time;trait;transcriptome sequencing;treatment strategy;Variant;Virulence;Virulence Factors;Work

PROJECT_TITLE: Understanding in vivo antibiotic resistance in diverse Pseudomonas aeruginosa populations

STUDY_SECTION: DDR

STUDY_SECTION_NAME: Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section[DDR]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Clinical Research;Contraception/Reproduction;Fibroid Tumors (Uterine);Women's Health Research

ORG_CITY: BALTIMORE

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Uterine fibroids are prevalent tumors of uterus characterized by excessive fibrotic tissues. Using new cutting-edge computational methods, we have found that small groups of senescent cells in fibroids work in concert with immune cells to produce soluble factors in fibroid tissues to create a feed-forward loop leading to fibrosis. This project seeks to unravel key cell-cell communication networks involving senescent and immune cells in fibroids to develop new treatments for uterine fibroids.

PI_NAMEs: BORAHAY, MOSTAFA A.;ELISSEEFF, JENNIFER H;SEGARS, JAMES H. (contact)

PROGRAM_OFFICER_NAME: TINGEN, CANDACE M

PROJECT_TERMS: Affect;Age;age related;beta-Galactosidase;CDKN2A gene;Cell Aging;Cell Communication;Cell Count;Cell Cycle;Cell secretion;cell type;Cells;Chronic;Coculture Techniques;collagenase;Communication;Computing Methodologies;cytokine;Data;Data Set;Development;Diabetes Mellitus;Disease;Drug Targeting;efficacy evaluation;Environmental Impact;Environmental Risk Factor;Exhibits;experimental study;Extracellular Matrix;Fibroid Tumor;Fibrosis;Flow Cytometry;Foreign Bodies;Foreign-Body Reaction;Growth;Heart Diseases;Hemorrhage;Hormones;Human;Hypoxia;idiopathic pulmonary fibrosis;Immune;Immune response;Immune system;Immunofluorescence Immunologic;immunoregulation;immunosenescence;Implant;implantation;In Vitro;in vivo;Infertility;inhibitor;learning algorithm;Leiomyoma;Macrophage;Maintenance;Modeling;Morphology;Mus;Myometrial;myometrium;new therapeutic target;Normal tissue morphology;Pathogenesis;Pathology;Pattern;Pelvic Pain;Pharmaceutical Preparations;Phase I Clinical Trials;Phenotype;Population;Prevalence;psychosocial;Public Health;Research;response;Role;senescence;senescence associated secretory phenotype;senescent cell;senolytics;single cell analysis;single-cell RNA sequencing;Stains;subcutaneous;System;T-Lymphocyte;Techniques;Testing;therapeutic target;Time;Tissues;transfer learning;Transgenic Model;Uterine Fibroids;Uterine Neoplasms;Uterus;vascular abnormality;Woman;Work;Xenograft procedure

PROJECT_TITLE: Role of senescent cells in uterine fibroid pathogenesis


PHR: PROJECT NARRATIVE Human cell division is regulated at the G1/S transition before DNA is replicated. The primary drivers of cells through the G1/S transition are the cyclin-dependent kinases Cdk4 and Cdk6 in complex with D-type cyclins. The goal of this project is to determine the mechanisms that Cyclin D-Cdk4/6 complexes use to drive cell division, to identify the targets of Cyclin D-Cdk4/6 kinases in cells, and to discover small molecules that inhibit Cyclin D’s ability to target substrates for phosphorylation by Cdk4/6.

PI_NAMEs: SKOTHEIM, JAN M (contact)

PROJECT_TERMS: Acute Lymphocytic Leukemia;Address;Alanine;Alleles;alpha helix;analog;Binding;Biochemistry;Biological Assay;Biological Sciences;C-terminal;Cancer Control;Cancer Model;cancer therapy;Cell Cycle Arrest;Cell division;Cell Line;Cell Proliferation;Cells;chemical genetics;Clinical Trials;Complex;Cyclin D1;Cyclin-Dependent Kinases;Cyclins;Data;delivery vehicle;design;DNA;Docking;Engineering;Enzymes;experimental study;Fluorescence Polarization;Fluorescence Resonance Energy Transfer;G1/S Transition;genetic approach;Goals;Human;improved;In Vitro;in vitro testing;in vivo;inhibitor;Knowledge;Libraries;Location;Malignant Breast Neoplasm;Malignant neoplasm of brain;Malignant Neoplasms;Molecular;molecular imaging;mouse model;Mus;Mutation;Neuroblastoma;Peptides;Pharmaceutical Preparations;Phenotype;phosphoproteomics;Phosphorylation;Phosphotransferases;Property;Protein Kinase;Proteomics;Reagent;Regulation;Retinoblastoma Protein;Role;Site;small molecule;small molecule libraries;structural biology;Structure;targeted cancer therapy;targeted treatment;Testing;Therapeutic;therapeutic target;tool;tumor;tumor growth;Xenograft procedure

PROJECT_TITLE: Project 1: Determine the mechanisms Cyclin D-Cdk4/6 uses to drive cell proliferation


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative / Public Health Statement The tumor suppressor p53 and proto-oncogene MYC are regulators of two of the most important pathways in preventing the development of human malignancies. This project will determine how p53 and MYC dynamics control cell fate responses to DNA damage. Completion of this research will aid in the development of methods to reduce fractional cell killing and cancer cell evasion of therapeutic treatments.

PI_NAMEs: BATCHELOR, ERIC  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Affect;Apoptosis;biological adaptation to stress;Breast Epithelial Cells;Bypass;cancer cell;cancer therapy;Cell Cycle Arrest;Cell Fate Control;Cell Fraction;cell killing;cell transformation;Cells;Cellular Stress;chemotherapy;Clustered Regularly Interspaced Short Palindromic Repeats;Data;Development;DNA Damage;Fluorescence Microscopy;Frequencies;gain of function;Gene Expression;Gene Expression Profiling;Gene Expression Regulation;gene repression;Genes;Genetic Transcription;genome editing;Genotoxic Stress;Goals;Health;Heterogeneity;Human;improved;Individual;innovation;insight;Malignant Breast Neoplasm;Malignant Neoplasms;Measurement;Mediating;method development;Microscopy;Modeling;Molecular;Mutagens;Mutation;MYC gene;neoplastic cell;novel;novel therapeutic intervention;Nucleic Acid Regulatory Sequences;Outcome;Pathologic;Pathway interactions;Pattern;pharmacologic;Physiologic pulse;Physiological;Population;prevent;programs;protein expression;Proteins;Proto-Oncogene Proteins c-myc;Proto-Oncogenes;Public Health;Recovery;Regulation;Repression;Research;Resistance;response;Role;senescence;Signal Pathway;Signal Transduction;Stimulus;Stress;System;temporal measurement;Testing;Therapeutic;Time;Tissues;TP53 gene;transcription factor;tumor;Variant;Work

PROJECT_TITLE: The roles of p53 and MYC dynamics in regulating heterogeneous cell fate responses to genotoxic stress

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: SAINT LOUIS

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: NARRATIVE: ECHO PROJECT Handoff standardization strategies have been implemented across hospitals to mitigate deleterious postoperative handoff events, but the "one-size-fits-all" approach has failed to promote critical collaborative handoff functions, consequently contributing to communication errors and care continuity failures. To address these failures, we propose to develop and implement the INTERACT (Intelligent interactive care continuity) handoff bundle, a flexible standardized, EHR-integrated, and resilient sociotechnical intervention comprised of a telemedicine-augmented handoff process (i.e., the social component) supported by a Machine Learning (ML)-augmented handoff report (i.e., the technical component). This project aligns with AHRQ’s patient safety initiatives for “making health care safer with higher quality care” and is responsive to PA-20-068 by rigorously testing an innovative solution to improve communication and coordination during care transitions.

PI_NAMEs: ABRAHAM, JOANNA  (contact)

PROGRAM_OFFICER_NAME: SWIGER, JAMES

PROJECT_TITLE: EnhanCed HandOffs (ECHO)

STUDY_SECTION: HITR

STUDY_SECTION_NAME: Healthcare Information Technology Research[HITR]


PHR: PROJECT NARRATIVE We investigate the molecular mechanisms of action of the Rb tumor suppressor and its two family members p107 and p130. A better understanding of the consequences of activating the Rb family in cancer cells will provide novel insights into how Cdk4/6 inhibitors block cancer progression and may help develop novel therapeutic approaches to enhance the effects of these inhibitors.

PI_NAMEs: SAGE, JULIEN  (contact)

PROJECT_TERMS: Acetylation;Affect;Alleles;Animal Model;Biochemical;Biological;Biological Assay;cancer cell;Cancer cell line;Cancer Control;cancer therapy;cancer type;candidate identification;CCNE1 gene;cdc Genes;Cell Cycle;Cell Cycle Arrest;Cell Cycle Inhibition;Cell Cycle Progression;Cell division;Cell model;Cells;Clinic;clinically relevant;Code;Compensation;Complex;CRISPR/Cas technology;Cyclin D1;Development;disabled;Dissociation;Doxycycline;Event;experimental study;Family;Family member;FDA approved;Future;gene repression;Genes;Genetic;genetic approach;Genetic Transcription;genome wide screen;Genomic approach;Genomics;Goals;Human;in vivo;inhibitor;insight;knock-down;Knock-out;lead candidate;loss of function;Lysine;Malignant Neoplasms;Measures;Molecular;Molecular Mechanisms of Action;Mus;mutant;Mutate;Mutation;neoplastic cell;novel;novel drug class;novel therapeutic intervention;overexpression;Patients;Phenotype;Phosphorylation;Phosphotransferases;pituitary gland development;Pituitary Neoplasms;Post-Translational Protein Processing;prevent;programs;protein complex;Proteomics;RB1 gene;Repression;Research;Resource Sharing;response;Retinoblastoma Protein;Role;small hairpin RNA;small molecule;System;Testing;tumor;tumor growth;tumor progression;Tumor Suppression;Tumor Suppressor Genes;Tumor Suppressor Proteins

PROJECT_TITLE: Project 2: To determine the consequences of activating Rb function in cancer cells


ORG_CITY: MADISON

ORG_NAME: WM S. MIDDLETON MEMORIAL VETERANS HOSP

ORG_STATE: WI

PHR: Melanoma is one of the five most frequently diagnosed cancers in VA patients. Veterans appear to be at higher risk of melanoma due to deployment to tropical/subtropical zones with high ultraviolet (UV)-index climates and exposure to certain chemicals. Despite recent advances in the treatment of melanoma, existing therapies are not able to fully manage melanoma incidences or fatalities. Therefore, new molecular targets and treatments will be required to effectively manage this cancer. The goal of this study is to define the role and mechanism of the protein SIRT6 in melanoma. SIRT6 plays complex roles in several other types of cancer, but its function in melanoma has not been fully established. We will investigate the role of SIRT6 and the therapeutic significance of inhibiting SIRT6 – alone and in combination with existing melanoma therapies – in several clinically-relevant models. The outcomes of our proposed study may lead to the development of novel diagnostic, prognostic and therapeutic approaches that will improve the management of melanoma in Veterans.

PI_NAMEs: AHMAD, NIHAL  (contact)

PROJECT_TERMS: ADP Ribose Transferases;Apoptosis;Autophagocytosis;blood glucose regulation;BRAF gene;cancer diagnosis;Cancer Patient;cancer type;CDK4 gene;Cell Cycle;Cell Migration Inhibition function;Cell Physiology;Cells;Chemicals;ChIP-seq;Climate;clinical investigation;clinically relevant;Co-Immunoprecipitations;Complex;Computer software;Coupled;CRISPR/Cas technology;Cyclin D1;Data;Development;Diagnosis;Disease;Disease Outcome;DNA Repair;Doxycycline;E-Cadherin;Epithelium;Exposure to;Family;Fibronectins;Future;Genetic Transcription;Goals;Growth;Growth and Development function;Healthcare;high risk;Human;imaging platform;improved;In Vitro;in vivo;Incidence;indexing;inhibitor;Intestines;Invaded;Investigation;Keratin-19;knock-down;Knock-out;Link;Liver;LOX gene;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;MEKs;melanocyte;Melanoma;Melanoma Cell;Melanoma patient;member;Mesenchymal;Metabolism;Metastatic Melanoma;migration;Mission;Modality;Modeling;Molecular;Molecular Profiling;Molecular Target;mouse model;Mus;N-Cadherin;Neoplasm Metastasis;Neoplasms;Nevus;NOD/SCID mouse;novel;novel diagnostics;Nuclear;Nuclear Protein;Outcome;overexpression;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;PET/CT scan;Play;pre-clinical;Process;prognostic;programs;Proteins;Proteomics;Publishing;Ras/Raf;Recurrence;Research;Resistance;response;RNA Interference;Role;Salicylic Acids;Sampling;senescence;Sir2-like Deacetylases;SIRT1 gene;Sirtuins;Skin;Skin Cancer;small hairpin RNA;small molecule;telomere;Therapeutic;Tissue Microarray;Tissues;transcriptome sequencing;tumorigenesis;ultraviolet;United States Department of Veterans Affairs;usability;Validation;Vertebral column;Veterans;Vimentin;Western Blotting;X-Ray Computed Tomography;Xenograft Model

PROJECT_TITLE: Role of sirtuin 6 in melanoma development and progression


ORG_CITY: Oakland

ORG_NAME: KAISER FOUNDATION RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE Because of recent policies to decrease opioid use, some people using long-term opioid therapy (LTOT) are encouraged or required to stop (discontinue) taking opioids. That has led experts to be concerned that patients whose LTOT is discontinued could have untreated pain, turn to other substance use and possibly illicit opioids, or have worsened mental health symptoms leading to suicide. To guide safer policies, guidelines, and care, this study will interview patients and doctors about discontinuing LTOT and use the results to develop a patient-centered decision aid to improve patient-provider communication around discontinuation of LTOT.

PI_NAMEs: HSU, CLARISSA WEN-LING (contact)

PROGRAM_OFFICER_NAME: ZHANG, XINZHI

PROJECT_TITLE: Patient Perspectives on Prescription Opioid Discontinuation: Understanding and Promoting Safe Transitions

STUDY_SECTION: HSQR

STUDY_SECTION_NAME: Healthcare Patient Safety and Quality Improvement Research[HSQR]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Chronic Pain;Interstitial Cystitis;Neurosciences;Pain Research;Urologic Diseases

PHR: Project Narrative This proposal will study neural circuits in the brainstem and spinal cord that process IC/BPS. A better understanding of the mechanisms of these circuits would greatly aid our ability to develop therapies for the treatment of IC/BPS.

PI_NAMEs: SAMINENI, VIJAY K (contact)

PROGRAM_OFFICER_NAME: MULLINS, CHRISTOPHER V

PROJECT_TERMS: Absence of pain sensation;Affect;afferent nerve;Analgesics;anatomical tracing;Behavioral;Bladder;Bladder Control;Bladder Diseases;bladder pain;Brain Stem;Cells;Central Nervous System;Chronic;chronic pain;Classification;Clinical;Cystitis;design;Development;Electric Stimulation;Electrophysiology (science);Equilibrium;Equipment and supply inventories;Etiology;Exhibits;Functional disorder;Genetic;Hypersensitivity;in vivo calcium imaging;insight;Interstitial Cystitis;Knowledge;Lead;Local Therapy;Maintenance;Molecular;Morphine;mouse model;Mus;neural circuit;neuromechanism;neuronal circuitry;Neurons;Neurotransmitters;Nociception;Opioid;optogenetics;Output;Pain;pain processing;Pathology;Pathway interactions;Pelvic Pain;Peripheral;Persistent pain;Pharmaceutical Preparations;pharmacologic;Population;Process;Property;receptor;Regulation;Resolution;response;Role;Slice;Spinal;Spinal Cord;Stimulus;Symptoms;Synapses;Syndrome;System;Testing;Therapeutic;therapeutic target;therapy development;transcriptome sequencing;transcriptomics;transmission process;United States;Woman;Work

PROJECT_TITLE: Neural Mechanisms Underlying IC/BPS

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


PHR: PROJECT NARRATIVE Tumor cells invariably have defects in the biochemical mechanisms that regulate cell growth and division. E2F proteins, which activate transcription of genes to drive forward the cell cycle and proliferation, are commonly turned on in cancer. This project aims to develop a molecular picture of how E2F proteins function and how they are switched on and off, with the goal of identifying strategies to develop therapeutics that act as E2F inhibitors.

PI_NAMEs: RUBIN, SETH MICHAEL (contact)

PROJECT_TERMS: Acetylation;Adaptor Signaling Protein;Address;Affinity;Architecture;Binding;Biochemical;Biochemistry;cancer cell;Cancer Control;Cancer Model;Cell Cycle;Cell Cycle Inhibition;Cell Cycle Progression;Cell Cycle Regulation;Cell division;cell growth;Cell Proliferation;Cells;Cellular Assay;Cellular biology;Chemicals;Chromatin;chromatin remodeling;Collaborations;Complex;Consensus;Cullin Proteins;cyclin F;Cyclin-Dependent Kinases;Cyclins;Data;Defect;Dependence;design;DNA;DNA biosynthesis;E2F transcription factors;Enzymes;Event;G1/S Transition;Gene Activation;Gene Expression;Genes;Genetic;Genetic Transcription;Genomic approach;Goals;Growth;Hydrophobicity;inhibitor;Interphase Cell;Knowledge;Malignant Neoplasms;Mediating;Mitosis;Modification;Molecular;Molecular Analysis;molecular imaging;Mutagenesis;neoplastic cell;novel;novel therapeutic intervention;Nucleosomes;Pathway interactions;Phenotype;Phosphorylation;Post-Translational Protein Processing;Post-Translational Regulation;programs;promoter;protein function;protein protein interaction;Protein Tyrosine Kinase;Proteins;Proteomics;reconstitution;recruit;refractory cancer;Regulation;Repression;Resolution;Retinoblastoma Protein;Route;S phase;Site;Specificity;structural biology;Structure;Substrate Cycling;Substrate Interaction;Testing;Therapeutic;therapeutically effective;Time;Tumor Suppressor Proteins;ubiquitin-protein ligase

PROJECT_TITLE: Project 3: Defining and targeting mechanisms of E2F transcription factor regulation


NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: ANN ARBOR

ORG_DEPT: BIOPHYSICS

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Biological oscillators widely exist in organisms ranging from bacteria to humans and have a significant impact on development, differentiation, and disease. The proposed research will connect the network design to the robust functions of biological oscillators, which will provide valuable guidance in search of targets to treat clock- related diseases or improve the clock performance.

PI_NAMEs: YANG, QIONG  (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Adult;Architecture;Bacteria;Biochemical;Biological Pacemakers;Biological Process;Biology;Cell Cycle;Cell division;Cell Nucleus;Cell Physiology;Cell-Free System;Cells;Circadian Rhythms;Comparative Study;Complex;computer studies;Cytoplasm;Defect;design;Development;Developmental Biology;Developmental Process;Devices;Discipline;Disease;Ecosystem;Embryo;Encapsulated;Environment;environmental change;experimental study;Feedback;Genetic;Goals;Human;Image;Impairment;improved;innovation;insight;interest;Knowledge;Link;Malignant Neoplasms;Microfluidics;Mitotic;Mitotic Cell Cycle;Modeling;Modification;Molecular;Mus;Neurons;Organism;Pattern;Performance;Periodicity;Physiology;Positioning Attribute;Process;Property;rational design;Reaction;reconstitution;Recording of previous events;Regulation;Research;resilience;response;Role;Shapes;Signal Pathway;simulation;Sleeplessness;somitogenesis;Structure;synthetic biology;System;Systems Biology;theories;Training;Zebrafish

PROJECT_TITLE: Understanding the robustness of cell cycles

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


NIH_SPENDING_CATS: Cancer;Genetics;Prevention

PHR: PROJECT NARRATIVE The overall program will study a genetic pathway that controls cell cycle progression and that is frequently mutated in human cancers. The function of the Administrative Core will be to promote scientific interactions among the Project Leaders and Core Leaders and their laboratory members, to provide guidance and oversight, and to facilitate communication among the members of the Projects and Cores, the greater scientific community, and the public. A long-term goal of this program is to help guide the development of new drugs for the treatment of human cancer.

PROJECT_TERMS: Advisory Committees;Awareness;Cancer Control;Cell Cycle Progression;Cell Cycle Regulation;Cell Differentiation process;Cell division;clinical application;cohesion;Collaborations;Communication;Communities;Community Outreach;Cyclin D1;data exchange;Development;Electronic Mail;Epigenetic Process;experience;experimental study;Family;Feedback;First Aid;Funding;gain of function mutation;Genes;Genetic;Genetic Transcription;Goals;Group Meetings;Human;Individual;interdisciplinary approach;Joints;Laboratories;loss of function mutation;Malignant Neoplasms;meetings;member;Mentorship;Monitor;Mutate;Newsletter;novel;novel therapeutics;Oncogenes;Oncoproteins;Participant;Pathway interactions;Peer Review;Phosphorylation;Play;Productivity;programs;Protein Family;Proteins;Protocols documentation;Publications;Research;Research Personnel;Research Project Grants;Role;Schedule;Series;Site;social media;symposium;Techniques;transcription factor;Transcriptional Regulation;Tumor Suppressor Genes;Tumor Suppressor Proteins;web site;Work

PROJECT_TITLE: Core A: Determining and targeting mechanisms controlling cancer cell division


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_CITY: BOSTON

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: Project Narrative The cochlea houses diverse types of neurons that collectively help animals to hear, locate and interpret a wide variety of sounds in the world. We will study how these neurons acquire the specialized properties needed for normal hearing, including the ability to withstand constant exposure to noise. Our work will improve the design of cochlear implants and inform efforts to repair the damaged cochlea, for example by replacing lost neurons.

PI_NAMEs: GOODRICH, LISA  (contact)

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Acoustic Nerve;Acoustic Trauma;Affect;Age;aged;Aging;AMPA Receptors;Anatomy;Animal Model;Animals;Auditory;Auditory Perception;Auditory Threshold;Automobile Driving;Birth;Brain;Brain Stem;calretinin;Cells;Cochlea;Cochlear Implants;Code;Complement;conditional knockout;Data;design;Dissection;Ear;Embryonic Development;Endowment;Exhibits;experimental study;Exposure to;falls;GATA3 gene;Gene Expression;Genes;Genetic;Genetic Transcription;Glutamate Receptor;Glutamates;Goals;Hair Cells;Hearing;Heterogeneity;hidden hearing loss;Human;improved;in vivo;Knockout Mice;Learning;Life;Maps;Molecular;molecular subtypes;Morphology;Mus;Mutant Strains Mice;Nature;nerve stem cell;neuron development;Neuronal Differentiation;Neurons;Noise;noise exposure;normal hearing;overexpression;Persons;Physiological;Population;postnatal;postsynaptic;presynaptic;progenitor;programs;Property;Regulation;repaired;response;ribbon synapse;Role;Side;Signal Transduction;single-cell RNA sequencing;SLC17A8 gene;sound;Specific qualifier value;spiral ganglion;Stimulus;Synapses;Temporal bone structure;Testing;Time;transcription factor;transcriptome;transcriptome sequencing;transmission process;Viral;Work

PROJECT_TITLE: Genetic dissection of auditory circuit assembly


PHR: Project narrative The Proteomics Core run by Dr. Peter Jackson will facilitate the analysis of protein-protein interactions, post- translational modifications, and the identification and analysis of protein complexes to comprehensively understand all paralogs of Cdk4/6, cyclin D1-3, Rb and E2Fs. By combining affinity-purification of wild type and mutant proteins, including mutations in protein modifications and patient-derived mutations, coupled to mass spectrometry, plus shotgun and phosphoproteomics techniques, and using a new ultrasensitive timsTOF mass spectrometer, this core will deliver state of the art data and analyses of the core proteins analyzed in all three projects of this grant. The high throughput of this facility and rapid data communication will be an important hypothesis generating function favoring new understanding of the molecular drivers of cancer linked to the cyclin D/CDK4/6 complex and those highly responsive to the clinically important cancer therapeutic palbociclib, a CDK4 inhibitor.

PI_NAMEs: JACKSON, PETER KENT (contact)

PROJECT_TERMS: Affect;Affinity Chromatography;Automobile Driving;Binding;Biological Markers;Biology;Cancer Control;CDK4 gene;Cell Cycle Regulation;Cell division;Cell Proliferation;Cell Survival;Cells;Chromatin;Clinical;clinical efficacy;Communities;Complex;Core Protein;Coupled;Cyclin D1;Cyclin-Dependent Kinase Inhibitor 2A;Cytoplasm;Data;data communication;Databases;Dependence;DNA Damage;E2F transcription factors;Ensure;Enzymes;experimental study;extracellular;Family;G1/S Transition;Gene Expression;Genes;Genetic Transcription;Global Change;Grant;Growth;Growth Factor;Guidelines;Head and Neck Cancer;inhibitor;insight;interest;Knock-out;Lead;Lesion;Link;Malignant Breast Neoplasm;Malignant neoplasm of esophagus;Malignant neoplasm of pituitary gland;Malignant Neoplasms;mass spectrometer;Mass Spectrum Analysis;Measurement;MEKs;Melanoma;member;Mitochondria;Molecular;mutant;Mutation;Nuclear;nucleocytoplasmic transport;Output;paralogous gene;Pathway interactions;Patients;Pharmaceutical Preparations;phosphoproteomics;Post-Translational Protein Processing;posttranscriptional;Protein Analysis;protein complex;protein protein interaction;Protein Structure Initiative;Proteins;Proteomics;Protocols documentation;Reporting;response;Retinoblastoma Protein;Running;Shotguns;Side;Signal Transduction;Site;Specificity;Standardization;Techniques;Testing;The Cancer Genome Atlas;Therapeutic;transcription factor;Transcriptional Regulation;Work

PROJECT_TITLE: Core B:  Proteomics Core.


PHR: PROJECT NARRATIVE The overarching goal this P01 proposal to better understand mechanisms in the core Cyclin D-Cdk4/6-Rb-E2F pathway regulating the G1/S transition controlling human cell division to facilitate development of novel cancer therapeutics. To test these hypotheses, all projects will rely on the cell phenotyping and molecular imaging core to generate mutations and analyze their effects on cell cycle progression and protein interactions. To support the program projects, this core aims to 1) use CRIPSR/Cas9 genome editing to generate mutant cell lines; 2) image gene expression, cell growth, and cell cycle transition dynamics at single cell resolution; and 3) build and maintain software that analyzes the terabytes of time lapse imaging data.

PROJECT_TERMS: Applications Grants;Biochemical;Biochemistry;Cancer Control;Cell Cycle;Cell Cycle Progression;Cell division;Cell Line;Cells;Cellular Assay;Communities;Computer software;CRISPR/Cas technology;Cyclin D1;Data;Dedications;Development;digital repositories;Dissociation;Dyes;experience;experimental study;Feedback;Fluorescence;fusion gene;G1/S Transition;Gene Deletion;Gene Expression;Generations;Genes;Genetic;Genetic study;genome editing;Goals;Human;Image;Image Analysis;imaging facilities;imaging software;improved;In Vitro;in vivo;interest;Laboratories;Ligation;live cell imaging;Malignant Neoplasms;Mass Spectrum Analysis;Measurement;Measures;Methods;Microscope;Microscopy;Mitotic Cell Cycle;Molecular;molecular imaging;mutant;Mutate;Mutation;novel;Pathway interactions;Phenotype;Phosphorylation Site;Process;programs;Protein Overexpression;protein protein interaction;Proteins;Regulation;Research Assistant;Resolution;Rest;Science;single cell analysis;Site;Spectrum Analysis;System;Technology;terabyte;Testing;Therapeutic;Time

PROJECT_TITLE: Core C: Cell Phenotyping and Molecular Imaging Core


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Complementary and Integrative Health;Digestive Diseases;Liver Disease;Microbiome;Nutrition;Prevention;Substance Misuse

ORG_CITY: LOUISVILLE

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: Project Narrative About 70% of alcohol use disorder patients do not develop severe alcohol-associated liver disease. The current project explores whether gut microbiota and their metabolites are key players determining transition from alcohol use disorders to severe alcohol-associated liver disease. Finally, therapeutic efficacies of microbial metabolite urolithin A against alcoholic liver diseases progression will be examined in humanized microbiota mice.

PI_NAMEs: JALA, VENKATAKRISHNA RAO (contact)

PROGRAM_OFFICER_NAME: WANG, JOE

PROJECT_TERMS: Accounting;alcohol research;alcohol use disorder;Alcoholic Liver Diseases;Alcohols;Attenuated;Bacteria;Berry;Cessation of life;Chronic;cigarette smoking;Cirrhosis;clinically significant;Colitis;Collaborations;Consumption;deter alcohol use;Development;Diet;Diet Habits;dietary;Dietary Practices;disability;Disease;disease model;Disease Progression;dysbiosis;Ellagi-Tannins;Ellagic Acid;Endotoxins;epidemiologic data;Exhibits;experience;experimental study;Fatty Liver;fecal transplantation;Fibrosis;Genetic;Germ-Free;Goals;gut microbiota;Health;Heavy Drinking;Hepatitis;high reward;high risk;Human;human subject;In Vitro;Inflammation;Intestinal permeability;Juglans;Laboratories;Liver diseases;liver inflammation;liver injury;Mediating;microbial;microbiome;microbiota;microbiota composition;Modeling;Molecular;mouse model;Mus;Obesity;Pathogenesis;Patients;Pilot Projects;Play;Pomegranate;Pre-Clinical Model;prevent;Preventive;Primary carcinoma of the liver cells;problem drinker;Production;Regulation;Rest;Risk Factors;Role;stool sample;Supplementation;Testing;Therapeutic;Treatment Efficacy

PROJECT_TITLE: Role of urolithin A in progression of alcohol-associated liver disease

STUDY_SECTION: AA

STUDY_SECTION_NAME: Biomedical Research Study Section[AA-1]


NIH_SPENDING_CATS: Brain Disorders;Cannabinoid Research;Endocannabinoid System Research;Epilepsy;Neurodegenerative;Neurosciences

ORG_DEPT: NEUROSURGERY

PHR: Tens of millions of people in the world are burdened by epilepsy, and many of these patients have seizures that cannot be controlled with existing therapies. There has been a recent surge in interest in leveraging cannabis-related molecules to control treatment-resistant epilepsy. Our project will determine how the body’s own cannabinoids get generated and released following neuronal hyperactivity in the intact brain. We will then test how effectively cannabinoid-sensitive inhibitory neurons can be targeted for novel non-invasive therapies to control chronic spontaneous seizures.

PI_NAMEs: LOSONCZY, ATTILA ;SOLTESZ, IVAN  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: 2-arachidonylglycerol;3-Dimensional;Acceleration;Address;Adult;Animals;Axon;Behavior;Behavioral;Biotechnology;Brain;Calcium;Cannabinoids;Cannabis;cell type;Cells;Cephalic;Chronic;CNR1 gene;complement C2a;Data;design;Development;Electroencephalography;Electrophysiology (science);endocannabinoid signaling;Endocannabinoids;Epilepsy;Exhibits;exogenous cannabinoid;Focused Ultrasound;G-Protein-Coupled Receptors;gamma-Aminobutyric Acid;Generations;Hippocampus;Hyperactivity;Image;in vivo;in vivo calcium imaging;information processing;inhibitory neuron;Injections;innovation;interest;Intervention;kainate;Knowledge;Ligands;Lipids;Measures;Mental disorders;Methods;Modality;Modeling;Monitor;mouse model;Mus;Myoepithelial cell;Nature;Nervous System Disorder;neuronal cell body;neuronal circuitry;Neurons;Neurotransmitters;novel;novel therapeutics;optogenetics;Patients;Pattern;Persons;Physiological;Pilocarpine;place fields;postsynaptic;presynaptic;Presynaptic Terminals;Process;Pyramidal Cells;receptor;Research Personnel;Resistance;Seizures;sensor;Sensory;Signal Transduction;spatiotemporal;Specificity;Syndrome;Temporal Lobe Epilepsy;Testing;Therapeutic;tool;Transgenic Mice;Treatment Efficacy;Treatment Side Effects;two-photon

PROJECT_TITLE: Activity-dependent endocannabinoid control in epilepsy

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

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

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: NARRATIVE The project aims at identifying novel drug combination therapies for AD/ADRD prevention and treatment using advanced informatics methods. We propose multiple strategies focusing on quantifiable screening and biological understanding using large healthcare databases and biology/pharmacogenomics knowledgebases. The project highlights on high-throughput drug combination screening mechanisms, integrative knowledge analysis models, and biological experiments covering different targets.

PI_NAMEs: JIANG, XIAOQIAN  (contact);ZHENG, WENJIN JIM

PROGRAM_OFFICER_NAME: ARUNKUMAR, NANDINI

PROJECT_TERMS: Adoption;Algorithms;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease related dementia;Alzheimer's disease therapy;big biomedical data;Big Data;Biological;Biological Markers;Biology;Cell model;Cells;Client;Clinical;Combination Drug Therapy;combinatorial;Complex;Computer Models;Data;Databases;Dementia;Development;Disease;drug candidate;Drug Combinations;drug discovery;Drug Modelings;drug repurposing;Drug resistance;Drug Targeting;effective therapy;efficacy validation;Electronic Health Record;experimental study;Fingerprint;gene interaction;Genes;graph neural network;Healthcare;healthcare burden;in silico;in vitro Model;in vivo;Informatics;Infrastructure;innovation;Investments;Joints;Knowledge;knowledgebase;Literature;Methods;Modeling;Molecular;multimodality;Mus;Neurodegenerative Disorders;neuropathology;novel;novel drug combination;novel therapeutics;Ontology;open source;Outcome;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacogenomics;Pharmacology;Pharmacotherapy;Phenotype;Philosophy;Population;Positioning Attribute;Prevention;Process;Protective Agents;Proteins;Research;Resources;Risk;screening;Side;side effect;Signal Pathway;simulation;software development;Source;Speed;Testing;tool;Toxic effect;user-friendly;Validation

PROJECT_TITLE: Finding combinatorial drug repositioning therapy for Alzheimer's disease and related dementias


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Aging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Patient Safety;Prevention;Primary Health Care

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: PROJECT NARRATIVE Polypharmacy, or taking multiple concurrent medications, is very common in older adults with cancer undergoing curative-intent chemotherapy. Polypharmacy is associated with adverse outcomes including receiving less chemotherapy, which in turn can affect cancer-related survival. “Deprescribing,” or the planned discontinuation of medications, is an intervention that can address polypharmacy, but it has not been studied in older adults with cancer receiving curative-chemotherapy; this proposal refines and tests two deprescribing intervention strategies in these patients.

PI_NAMEs: RAMSDALE, ERIKA E (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Address;Adherence;Adopted;adverse outcome;Advocate;Affect;age related;Aging;Area;arm;beneficiary;Benefits and Risks;Board Certification;cancer care;cancer therapy;care delivery;career development;Caring;chemotherapy;Client satisfaction;Clinic;Clinic Visits;Clinical;Clinical Data;Clinical Pharmacists;Clinical Trials Design;Cluster randomized trial;cohort;Collaborations;Community Clinical Oncology Program;Dangerousness;Data;Data Science;Development Plans;Dose;Educational Intervention;efficacy outcomes;Elderly;end of life;Enrollment;falls;Focus Groups;functional status;Geriatrics;Goals;Holly;Hospitalization;implementation barriers;implementation facilitators;implementation outcomes;implementation science;implementation strategy;improved;improved outcome;Informatics;innovation;Intervention;Interview;Knowledge;Malignant Neoplasms;Measures;Medicare;Medicine;Mentors;Mentorship;Methodology;Methods;multidisciplinary;National Cancer Institute;Nurses;older adult;older patient;Oncologist;Oncology;Outcome;outcome prediction;Patient Education;Patients;Pharmaceutical Preparations;Pharmacists;Phase;Physical Function;Polypharmacy;Population;post intervention;pragmatic trial;Prevalence;primary care provider;Process;professor;programs;Protocols documentation;Qualitative Methods;randomized, clinical trials;Reporting;Research;research and development;Research Personnel;Resources;secondary analysis;Series;skills;statistics;Structure;survival prediction;survivorship;symposium;Symptoms;technology intervention;Testing;Time;Toxicity due to chemotherapy;Training;trial design;Universities;Withdrawal;Work

PROJECT_TITLE: Decreasing Polypharmacy in Older Adults with Curable Cancers

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


ORG_CITY: LEAWOOD

ORG_NAME: NORTH AMERICAN PRIMARY CARE RES GROUP

ORG_STATE: KS

PHR: Project Narrative The purpose of the proposed national Practice-Based Research Network (PBRN) conferences to be convened annually from 2023 through 2025 is to enhance the skills and knowledge of clinicians and researchers in evidence-based research to improve the health of the U.S. population and the value of health care patient safety. The Agency for Healthcare Research and Quality (AHRQ) conference grant to support these PBRN meetings will assist AHRQ in accomplishing its mission to create evidence that will make health care safer, higher quality, more accessible, equitable and affordable; the conference intends to ensure the produced evidence is summarized, communicated, and applied among clinicians and researchers.

PI_NAMEs: COLE, ALLISON  (contact)

PROJECT_TITLE: National Practice-Based Research Network Conferences 2023 to 2025

STUDY_SECTION: HEOR

STUDY_SECTION_NAME: Healthcare Effectiveness and Outcomes Research[HEOR]


ORG_CITY: HERSHEY

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: PROJECT NARRATIVE  There are significant unmet needs for youth with Autism Spectrum Disorder (ASD) leading to increased crises and emergencies, which are exacerbated during the COVID-19 pandemic. This study will examine the interplay between polypharmacy of psychotropic medications and key ASD behavioral treatments, as well as their impact on psychiatric adverse events in a real-world setting. Our findings will have significance to the entire ASD community by informing individuals, families, and providers on effective treatments for reducing the risk of behavioral health crises and guiding policy decision-making at the payer, state, and national levels.

PI_NAMEs: LIU, GUODONG  (contact)

PROGRAM_OFFICER_NAME: SAGATOV, ROBYN

PROJECT_TITLE: The interplay of behavioral therapies, pharmacological treatments and psychiatric adverse events among Youth with Autism Spectrum Disorders


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

ORG_CITY: GALVESTON

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because of the positive impact of preventing early synaptic dysfunction that can prevent progression of cognitive deficit thus benefitting the drive the development of effective therapy for Alzheimer’s disease and related dementia and improving quality of life. The proposed research is aligned to NIH’s mission of fostering creative discoveries to protect and improve health.

PI_NAMEs: KRISHNAN, BALAJI  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: 3xTg-AD mouse;abeta oligomer;AD transgenic mice;Address;adeno-associated viral vector;Affect;Age;Age of Onset;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease related dementia;Amyloid;Attention;Automobile Driving;Autopsy;Behavioral;Biochemical;Brain;brain tissue;Cause of Death;Clinical Trials;Co-Immunoprecipitations;cofilin;Cognitive deficits;Creativeness;Data;Dementia;Dendritic Spines;Development;Disease;effective therapy;Electrophysiology (science);Etiology;Event;Fluorescence;Fostering;Frontotemporal Dementia;Functional disorder;Future;Goals;halopemide;Health;Hippocampus;Human;imaging study;Impaired cognition;improved;inhibitor;insight;Knowledge;Long-Term Potentiation;Mechanics;Mediating;Memory;Memory impairment;Mission;Molecular;mouse model;Mus;Nerve Degeneration;Neurons;neuropathology;novel;overexpression;Patients;Phospholipase D;phospholipase D1;pre-clinical;preclinical study;prevent;PRKCA gene;Protein Isoforms;Proteins;Proteomics;Public Health;Publishing;Quality of life;recruit;Reporting;Research;Role;Signal Transduction;Sirolimus;small hairpin RNA;small molecule;small molecule inhibitor;Synapses;synaptic function;Synaptosomes;tau Proteins;Tauopathies;Temporal Lobe;Testing;Therapeutic;Therapeutic Intervention;therapeutically effective;Transgenic Mice;United States National Institutes of Health;Up-Regulation;vector;Western Blotting

PROJECT_TITLE: Phospholipase D1 Mediated Early Events Affecting Synaptic Dysfunction in Alzheimer's Disease and Related Dementia


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Back Pain;Biomedical Imaging;Chronic Pain;Clinical Research;Pain Research

ORG_CITY: LA JOLLA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative The goal of this study is to further develop a 3D UTE-AdiabT1r sequence for robust mapping of PGs, a 3D UTE-MT sequence for robust mapping of MMF, an IR-FS-UTE sequence for high contrast imaging and T2* mapping of the CEP to evaluate calcification and dehydration, and a UTE-DESS sequence to study apparent diffusion coefficient (ADC) for evaluating IVD degeneration in lumbar spines from young (<40y, n=10), mid-age (40-70y, n=10), and elderly (>70y, n=10) donors. This study will further validate the series of UTE sequences developed to assess IVD degeneration and regeneration using a mature rabbit annular puncture chronic disc degeneration model. In the final step, the optimized UTE sequences will be used to study IVD degeneration in patients with chronic LBP (n=40) and age-, sex- and BMI-matched healthy volunteers (n=40), compare UTE and clinical MRI metrics of the NP, AF, and CEP of the lumbar spine in the two groups, and correlate them with clinical evaluations.

PI_NAMEs: MA, YAJUN  (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: 3-Dimensional;Address;Affect;Age;Animals;Biochemical;Biochemistry;Biological Markers;Body mass index;calcification;cartilaginous;Chronic;Chronic low back pain;Clinical;Collagen;Complex;contrast imaging;Dehydration;Development;Diagnosis;Diffusion;disability;disc regeneration;Elderly;Evaluation;Fiber;Frequencies;glucose transport;Goals;growth differentiation factor 6;Health;Health Care Costs;healthy volunteer;Histologic;Histology;Hydration status;Image;Imaging Techniques;Inferior;Injections;Intervertebral disc structure;intervertebral disk degeneration;Location;Low Back Pain;Magic;Magnetic Resonance Imaging;Maps;Measures;Modeling;non-invasive imaging;nucleus pulposus;Nutrient;Oryctolagus cuniculus;oxygen transport;Pain;Patients;Population;Proteoglycan;Puncture procedure;Quality of life;Recovery;Reference Standards;Relaxation;Research;research clinical testing;Saline;Sampling;saturated fat;Series;sex;SF-36;Signal Transduction;Specimen;Techniques;Testing;Time;Tissues;Translating;translational study;Vertebral column;wasting

PROJECT_TITLE: Ultrashort Echo Time Magnetic Resonance Imaging of the Lumbar Intervertebral Disc.

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health

ORG_CITY: Los Angeles

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Project Narrative India provides a unique context with which to disentangle the effect of bilingualism on cognitive aging because bilingualism is much more equally distributed among socioeconomically diverse groups in India than it is in Western and high-income countries. Leveraging already-funded, rich population representative data from India, the findings of the proposed investigation will yield new insights on the intersection of bilingualism and cognitive aging, discerning whether bilingualism buffers the effects of blood-based and neuroimaging biomarkers of Alzheimer’s Disease and Related Dementias (ADRD) and uncovering the mechanisms by which bilingualism confers cognitive reserve against biological risk of ADRD.

PI_NAMEs: AKSMAN, LEON ;ARCE, MIGUEL ;LEE, JINKOOK  (contact)

PROGRAM_OFFICER_NAME: SUTTERER, MATTHEW

PROJECT_TERMS: Address;Age;Age Years;Aging;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid;Attention;bilingualism;Biological;Biological Markers;Blood;Blood specimen;Blood Tests;brain health;Brain region;brain volume;Buffers;cerebral atrophy;Cognition;Cognitive;Cognitive aging;cognitive function;cognitive reserve;cognitive testing;Communities;Country;Data;Dementia;dementia risk;Diagnostic;Education;Elderly;Environmental Risk Factor;ethnic diversity;executive function;experience;Family;Frequencies;Funding;Geographic Locations;Health;health determinants;Healthcare;Impaired cognition;Income;India;Individual;insight;Intervention;Interview;Investigation;Language;Language Development;late life;Life Cycle Stages;Linguistics;literacy;low and middle-income countries;machine learning method;Magnetic Resonance Imaging;Measures;Memory;Methodology;modifiable risk;mortality;Multilingualism;neuroimaging;neuroimaging marker;neuropathology;older adult;Older Population;Outcome;Participant;Pathology;Pathway interactions;Personal Satisfaction;Persons;Plasma;Population;Population Heterogeneity;Prevention;promote resilience;protective effect;Public Health;Recording of previous events;Reporting;Research;resilience;resilience factor;response;Risk;Risk Factors;Role;rural residence;Sampling;Schedule;Schools;social;Social Class;social culture;sociocultural determinant;sociodemographics;Socioeconomic Status;socioeconomics;Standardization;Subgroup;tau Proteins;Testing;Thick;Variant;Venous;white matter;Work

PROJECT_TITLE: Multilingualism as a factor of resilience to Alzheimer's disease and related dementias in India


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences;Substance Misuse

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Project Narrative Alcohol use disorder imposes a substantial public health burden. Despite this, effective therapies are lacking, and treatment for compulsive drinking is particularly inadequate. This research seeks to understand how chronic ethanol exposure disrupts specific brain circuits that are required for compulsive alcohol drinking. The data gathered from this study will provide novel therapeutic strategies targeting compulsive alcohol drinking.

PI_NAMEs: MATHUR, BRIAN NEIL (contact)

PROGRAM_OFFICER_NAME: LIU, QI-YING

PROJECT_TERMS: Ablation;Acute;Adenylate Cyclase;Affect;Alcohol consumption;alcohol effect;alcohol exposure;alcohol use disorder;Alcohols;Alzheimer's Disease;Animals;Behavioral;Biology;Brain;Cell Nucleus;cell type;Cells;cellular imaging;Chemosensitization;Chronic;Corpus striatum structure;Data;Digestion;Dorsal;Down-Regulation;drinking;drinking behavior;Economics;effective therapy;Electrophysiology (science);Ethanol;Exposure to;Extracellular Matrix;Extracellular Matrix Degradation;Functional disorder;functional loss;Funding;gamma-Aminobutyric Acid;Genes;Genetic;genetic approach;Globus Pallidus;Grant;habit learning;Habits;Image;imaging approach;Imaging Techniques;in vivo;insight;Interneurons;Ischemic Stroke;Learning;Mediating;Molecular;molecular imaging;Mus;neural circuit;neuropsychiatric disorder;new therapeutic target;novel therapeutic intervention;Occupational;optogenetics;Outcome;patch clamp;Pathologic;Pharmacology;Phenotype;Physiology;Population;Positioning Attribute;presynaptic;protein expression;Public Health;Regulation;Research;response;Rewards;single nucleus RNA-sequencing;Slice;social;Societies;Specific qualifier value;Synapses;Synaptic Transmission;System;Testing;Thalamic structure;tool;transmission process;vapor

PROJECT_TITLE: Striatal Microcircuit Dynamics of Ethanol Habits

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Gene Therapy;Genetics;Human Genome;Immunotherapy;Orphan Drug;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Oncolytic viruses are viruses with selective ability to replicate in cancer cells and are increasingly recognized for their potential to activate an immune response to cancers. In the current proposal, we will aim to determine how the immune responses to oncolytic viruses impact the development of anti-tumor immunity in animal models and patients. These findings will bear direct impact on the oncolytic virus engineering strategies and will guide the design of clinical trials implementing these agents in combination with other immunotherapies.

PI_NAMEs: ZAMARIN, DMITRIY  (contact)

PROGRAM_OFFICER_NAME: SINGH, ANJU

PROJECT_TERMS: adaptive immune response;Adenoviruses;Adoptive Transfer;Animal Model;anti-PD-L1 antibodies;anti-tumor immune response;Antigen-Presenting Cells;antiviral immunity;Bilateral;Blood;cancer cell;CD8-Positive T-Lymphocytes;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Chemosensitization;Clinical;clinical predictors;Clinical Trials;Clinical Trials Design;Clone Cells;Colorectal Cancer;Computational Biology;congenic;Data;Development;Distant;DNA;DNA Viruses;emerging virus;Engineering;Ensure;Equilibrium;Exhibits;Future;Genetic;Genetic Engineering;Human;immune checkpoint blockade;Immune response;Immune system;Immunity;Immunologics;Immunology;Immunotherapy;in situ vaccination;intraperitoneal;Investments;Knowledge;Malignant neoplasm of ovary;Malignant Neoplasms;Measures;Mediating;Melanoma;Microscopy;Modeling;mouse model;Mus;Nature;neoplastic cell;Newcastle disease virus;Oncogenic Viruses;Oncolytic;oncolytic adenovirus;oncolytic virotherapy;Oncolytic viruses;Outcome;Ovarian Carcinoma;Patients;Peripheral;peripheral blood;Peritoneal;Phenotype;pre-clinical;Primary Neoplasm;response;RNA;RNA Viruses;Simplexvirus;single-cell RNA sequencing;Site;synergism;T cell receptor repertoire sequencing;T cell response;T-Cell Receptor;T-cell receptor repertoire;T-Lymphocyte;Testing;Therapeutic;tool;transcriptome sequencing;Treatment Efficacy;tumor;Tumor Expansion;Tumor Immunity;tumor microenvironment;Tumor-Infiltrating Lymphocytes;Vaccinia;Viral;Viral Antigens;virology;Virus

PROJECT_TITLE: POTENTIATION OF ANTI-TUMOR IMMUNITY BY ONCOLYTIC VIRUS IN SITU VACCINATION

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it provides evidence on how health systems— through which a growing proportion of medical care is delivered in the United States—influence care of older Americans with the greatest health needs. Understanding whether and how health systems change quality, utilization, and spending for medically complex Medicare beneficiaries is critical for implementing care models and policies that improve the health of medically complex patients. The proposed research is relevant to AHRQ's mission as it pertains to generating knowledge that contributes to improving care for vulnerable populations and promoting a higher value health care system.

PI_NAMEs: BOND, AMELIA  (contact);KHULLAR, DHRUV

PROJECT_TITLE: Health Systems and High-Need Populations: The Effect of Vertical Integration on Utilization, Spending, and Quality for Medically ComplexPatients

STUDY_SECTION: HSVR

STUDY_SECTION_NAME: Healthcare Systems and Values Research[HSVR]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Autism;Brain Disorders;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE Precise control of kinase signaling pathways is critical for neuronal development and function. Mutations in the understudied serine-threonine kinase TAOK1 are strongly associated with both autism and neurodevelopmental delay. Integrating innovative approaches in kinase biochemistry, proteomics, chemical-genetics, structural biology and stem cell modeling, we will determine the molecular function of TAOK1 kinase and determine how TAOK1 dysfunction contributes to the etiology of neurodevelopmental disorders.

PI_NAMEs: YADAV, SMITA  (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: Amino Acids;autism spectrum disorder;Binding;Biochemical;Biochemistry;Biological;Biological Assay;Biological Models;Biology;Catalytic Domain;Cell membrane;Cerebral cortex;chemical genetics;comparative;Data;Development;Disease;DNA Sequence Alteration;Electrophysiology (science);Etiology;excitatory neuron;experimental study;Functional disorder;Genes;Genetic Engineering;Growth;Hippocampus;Human;human disease;Human Engineering;human induced pluripotent stem cells;human stem cell-derived;In Vitro;Induced pluripotent stem cell derived neurons;induced pluripotent stem cell technology;Inherited;inhibitor;innovation;Investigation;Lead;Lipid Binding;Liposomes;Macrocephaly;Mediating;Membrane;migration;Modeling;Molecular;Molecular Conformation;Molecular Structure;Morphology;mutant;Mutation;nerve stem cell;Neurodevelopmental Disorder;neurogenesis;neuron development;neuronal growth;Neurons;Neuropathogenesis;neuropathology;Organoids;Pathogenesis;Pathway interactions;Phosphatidylinositols;Phospholipids;phosphoproteomics;Phosphorylation;Phosphotransferases;Property;Protein Kinase;Protein Truncation;Protein-Serine-Threonine Kinases;Proteins;Proteomics;reconstitution;Research Proposals;Role;Signal Pathway;Signal Transduction;stem cell model;stem cell technology;structural biology;Synapses;Testing;three-dimensional modeling;Vertebral column;X-Ray Crystallography

PROJECT_TITLE: Kinase Dysfunction in Autism and Neurodevelopmental Disorders

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MDCN-P(57)]


NIH_SPENDING_CATS: Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Wound Healing and Care

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: Project Narrative The overarching goal of the proposed research is to develop new molecular treatments to prevent or attenuate vocal fold scarring following mucosal injury. Such voice problems are debilitating and can cause significant personal and occupational difficulties, loss of income, and reduced quality of life.

PI_NAMEs: WELHAM, NATHAN  (contact)

PROGRAM_OFFICER_NAME: KOPF, LISA MARIE

PROJECT_TERMS: Anatomy;Animals;Area;Attenuated;Biological Assay;Biology;Biomechanics;Bone Marrow;Bone Marrow Cells;Bone Marrow Transplantation;Cell Lineage;cell motility;Cells;Chimera organism;Cicatrix;Clinical;Development;Dysphonia;effective therapy;Engraftment;experimental study;Extracellular Matrix;Fibrosis;Foundations;Funding;Future;gain of function;Genetic Techniques;Germ Cells;Goals;Human;Immune system;immunodeficiency;Immunology;Impairment;improved;in vivo Model;Income;Individual;Inflammatory;injured;Injury;Interruption;Label;loss of function;Maintenance;Measures;Migration Assay;Modeling;Molecular;monocyte;Mucous Membrane;Mus;Myeloid Progenitor Cells;Occupational;Outcome;Pathologic;Patients;Performance;Phonation;Physiological;Physiology;Play;Population;Population Heterogeneity;pre-clinical research;predictive modeling;prevent;primary outcome;Prophylactic treatment;Quality of life;Rattus;recruit;repaired;Research;response;Rodent;Role;Series;Signal Transduction;Therapeutic;Tissues;transplant model;Treatment outcome;vocal cord;Voice;Work;wound healing;wound treatment

PROJECT_TITLE: Characterization and treatment of the scarred vocal fold

STUDY_SECTION: MFSR

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


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Childhood Injury;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Serious Mental Illness;Social Determinants of Health;Suicide;Suicide Prevention;Violence Research;Youth Violence

PHR: PROJECT NARRATIVE The rates of suicide and suicidal ideation and behaviors (SIB) among Black youth have almost doubled in the past decade, making the studying of Black youth suicide and SIB a public health priority. The proposed study aims to improve our understanding of the uniqueness and complex etiology of Black youth suicide and SIB through a multi-dimensional approach, including the identification of risk and protective factors and an empirical evaluation of Durkheim’s social integration theory and Tarde’s imitation theory on Black youth suicide and SIB. The results of the study will provide valuable information for future policies targeting suicide reduction among the Black youth population.

PI_NAMEs: XI, WENNA  (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: 13 year old;Aborigine;Address;Adopted;Affect;aged;Alcohol consumption;Area;Automobile Driving;Award;Behavior;Belief;Big Data;Black race;career;Clinical;Clinical Data;clinical risk;Competence;Complex;contagion;County;Data;Databases;Dedications;design;Dimensions;Disparity;effective intervention;Electronic Health Record;Ethnic Origin;Etiology;Evaluation;Factor Analysis;Feeling suicidal;Foundations;Future;Geographic Distribution;Geography;Goals;health disparity;Healthcare Systems;Hispanic;Human;improved;indexing;Individual;Intervention;Inuits;Knowledge;Life;Location;machine learning model;marijuana use;Measures;Medical History;Mental Health;Modeling;mortality;mortality risk;multidisciplinary;National Institute of Mental Health;Nature;Neighborhoods;New York City;novel;Persons;Phase;Policies;Population;pre-doctoral;Prevention;protective factors;Public Health;public health priorities;Race;Racial Segregation;reducing suicide;Research;Research Personnel;residential segregation;Risk;Risk Behaviors;Risk Factors;Risk Reduction;Risk Reduction Behavior;Sampling;social;social factors;social integration;spatiotemporal;statistical and machine learning;suicidal;suicidal adolescent;suicidal behavior;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;Suicide prevention;suicide rate;System;Testing;theories;Time;Training;Work;Youth

PROJECT_TITLE: Risk and protective factors for Black youth suicide and suicidal ideation and behaviors


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Data Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Heart Disease - Coronary Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Nutrition;Obesity;Prevention;Social Determinants of Health

ORG_CITY: CLEVELAND

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Narrative We will create artificial intelligence methods for quantitative assessment of heart disease using a fast, inexpen- sive computed tomography (CT) imaging method. With success, our research will lead to improved evaluation of heart disease, paving the way for personalized treatments. It will also enable many research studies on oth- er risk factors such as diabetes.

PI_NAMEs: RAJAGOPALAN, SANJAY ;WILSON, DAVID LYNN (contact)

PROGRAM_OFFICER_NAME: REIS, JARED P

PROJECT_TERMS: abdominal fat;Adherence;Adipose tissue;African American population;Agatston Score;Age;Agonist;Anticoagulants;Aorta;Archives;artificial intelligence method;Atherosclerosis;Big Data;Blood Platelets;Blood Vessels;Brown Fat;Cadaver;calcification;Calcium;Cardiometabolic Disease;cardioprotection;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;Cardiovascular system;Cause of Death;Charge;Chest;Classification;Clinical;Clinical Data;clinical risk;Clinical Trials;cohort;Cohort Studies;commercialization;comorbidity;Computer software;Coronary;Coronary artery;coronary artery calcification;Coronary Artery Risk Development in Young Adults Study;cost;Counseling;Data;Data Reporting;data repository;Data Set;Decision Making;deep learning;density;Diabetes Mellitus;Disease;disease phenotype;dosage;Elasticity;Engineering;Evaluation;Event;Fatty acid glycerol esters;Future;GCG gene;Genes;Grouping;Heart;Heart Diseases;Hepatic;high risk;Image;imaging modality;improved;Individual;Inferior;Inflammation;inhibitor;innovation;Institution;interest;Knowledge;large datasets;Link;Machine Learning;Mediastinal;Metabolic;metabolomics;Methodology;Methods;Modeling;Morphology;neural network;novel;Obesity;Oncology;Participant;Pathologic;Patients;personalized medicine;Pharmaceutical Preparations;Phenotype;Preventive therapy;programs;Psoriasis;Race;radiomics;Recommendation;Reproducibility;Research;research study;Risk;Risk Factors;Risk Marker;risk prediction;risk stratification;Role;Scanning;Screening procedure;Shapes;side effect;Site;Socioeconomic Status;socioeconomics;statistics;success;Surface;Technology Transfer;Testing;Texture;Therapeutic;time use;Tissues;University Hospitals;Work;X-Ray Computed Tomography

PROJECT_TITLE: Cardiovascular risk from comprehensive evaluation of the CT calcium score exam


ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

PHR: Project Narrative The proposed study will determine how pathological stress on the heart induces metabolic adjustments to both the heart and adipose tissue, and how these reciprocal responses mediates both cardiac metabolic remodeling and the development of decompensated cardiac hypertrophy with potential consequences to systemic metabolism. We will first test the role of cardiac natriuretic peptide responses to altered cardiac fat oxidation as an activator of adipose tissue plasticity, independent of adrenergic activation of adipose tissue, and second, examine the potential for a cardioprotective role of the beiging of white adipose tissue and brown adipose tissue activation.

PI_NAMEs: LEWANDOWSKI, E DOUGLAS (contact);STANFORD, KRISTIN I

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Adipocytes;adipokines;Adipose tissue;Adrenergic Agents;Adrenergic Receptor;Affect;Agonist;antagonist;aorta constriction;Aortic Valve Stenosis;Blood Vessels;Brown Fat;Cardiac;cardioprotection;Carnitine Palmitoyltransferase I;Catecholamines;Characteristics;comorbidity;Data;Development;Diabetes Mellitus;EFRAC;Enzymes;event cycle;Fatty acid glycerol esters;fatty acid metabolism;fatty acid oxidation;Female;Genes;glucose tolerance;Heart;Heart failure;heart failure with reduced ejection fraction;Heart Hypertrophy;heart metabolism;Human;Hypertrophy;improved;insight;Insulin Resistance;insulin sensitivity;interest;knock-down;Laboratories;Link;lipid metabolism;Lipids;Lipolysis;Liver;long chain fatty acid;male;Mediating;Mediator;Metabolic;Metabolic dysfunction;Metabolic stress;Metabolism;Mitochondria;Modeling;mouse model;Mus;Myocardial tissue;Myocardium;Myosin Heavy Chains;Natriuretic Peptides;natural hypothermia;novel;Nutrient;Obesity;Organ;Outcome;overexpression;oxidation;Pathogenesis;Pathologic;Patients;Peripheral;Phase;Phenotype;preservation;pressure;Production;Protein Isoforms;Publishing;Rattus;Receptor Activation;Receptors, Adrenergic, beta-3;remediation;Research;Research Design;response;Role;sex;Sex Differences;Signal Transduction;Source;stem;Stress;subcutaneous;Testing;Thermogenesis;Tissue Transplantation;uncoupling protein 1;uptake;virtual

PROJECT_TITLE: Adipose tissue mediates cardiac metabolic remodeling in the pathologically stressed heart in the absence of  primary metabolic stress

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


NIH_SPENDING_CATS: Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences

PHR: Considerable evidence suggests that synaptic functions is severely compromised in neurodegenerative and neuropsychiatric diseases, exerting a huge toll on human health and our society. Our proposed study is to examine the role of three PP1 isoforms, including the human de novo mutation in PP1β, and their signaling mechanisms underlying CNS synaptic functions. The results obtained from these studies will provide molecular insights into potential therapeutic cures for treating patients with neuro-degenerative or neuropsychiatric diseases.

PI_NAMEs: XIA, HOUHUI  (contact)

PROJECT_TERMS: Biological Models;C-terminal;Catalytic Domain;Cognition;Cognitive deficits;Compensation;Complement;conditional knockout;de novo mutation;Dendritic Spines;density;developmental disease;Disease;F-Actin;Genes;Goals;Health;Hippocampus;Holoenzymes;Human;Impairment;in vivo;insight;Intellectual functioning disability;knock-down;Knock-out;Knockout Mice;Knowledge;Long-Term Potentiation;loss of function;Mammalian Cell;Mediating;Memory;Molecular;Morphogenesis;Motility;mouse model;Mus;Muscle relaxation phase;mutant;myosin phosphatase;Myosin Regulatory Light Chains;Neurabin;Neurodegenerative Disorders;Neurons;neuropsychiatric disorder;new therapeutic target;non-muscle myosin;Nonmuscle Myosin Type IIB;Patients;Phosphoric Monoester Hydrolases;Phosphorylation;Play;polymerization;Polymers;prevent;Process;Protein Dephosphorylation;Protein Isoforms;Protein phosphatase;Reagent;Role;Scaffolding Protein;Serine;Serine/Threonine Phosphorylation;severe intellectual disability;Signal Transduction;small hairpin RNA;Societies;spatial memory;Structure;Synapses;synaptic function;synaptic inhibition;Synaptic plasticity;Synaptic Transmission;Terminator Codon;Testing;Therapeutic;Therapeutic Intervention;Vertebral column;Work

PROJECT_TITLE: Protein phosphatase 1 isoforms, human de novo mutations and synaptic functions

STUDY_SECTION: PMDA

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Precision Medicine;Rehabilitation;Serious Mental Illness

ORG_CITY: DALLAS

ORG_DEPT: PSYCHIATRY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PUBLIC HEALTH RELEVANCE Major depressive disorder is the second leading cause of global disability and results in significant functional impairment, morbidity, and mortality. Despite evidence of impairments associated with emotionally-laden (i.e., hot) cognitive processes and behaviors, there remains significantly limited information regarding hot cognitive function in adults across the lifespan with depression that hinders mechanistic understanding and new treatment development. The knowledge gained in this preliminary pilot study will provide the necessary information to create a program of research to inform underlying mechanisms of hot cognitive function and confirm such mechanisms of action to then develop new and personalized mechanism-based therapeutics to remediate hot cognitive dysfunction and optimize overall health outcomes.

PI_NAMEs: GREER, TRACY L.;MCCLINTOCK, SHAWN M (contact)

PROGRAM_OFFICER_NAME: LYONS, ELIZABETH ANNE

PROJECT_TERMS: Adult;Affect;Age;age effect;anti-depressive agents;Area;Attention;attentional bias;Behavior;Behavioral;Behavioral Mechanisms;Benchmarking;Biometry;Brain;Brain region;Categories;Chronic;Clinical;Clinical Research;clinically significant;Cognition;Cognitive;Cognitive aging;cognitive control;cognitive function;cognitive process;Cognitive remediation;cognitive task;Cognitive Therapy;Color;Data;Depressed mood;disability;Disabling;Disease;Emotional;emotional stimulus;Emotions;Enrollment;executive function;Foundations;Functional disorder;Functional impairment;Goals;Health;Image;Impaired cognition;Impairment;improved;Impulsivity;Individual;Infrastructure;innovation;invention;Investigation;Knowledge;life span;Magnetoencephalography;Major Depressive Disorder;Measurement;Measures;Memory;Mental Depression;Methods;Modeling;Morbidity - disease rate;mortality;National Institute of Mental Health;neural;neural circuit;neuroimaging;Neuropsychology;neuroregulation;Neurosciences;Nomenclature;older adult;Outcome;Patient-Focused Outcomes;personalized medicine;personalized therapeutic;Phenotype;Pilot Projects;Positioning Attribute;Process;programs;Protocols documentation;public health relevance;Quality of life;remediation;Research;Research Domain Criteria;Research Support;Resources;Rest;reward processing;social cognition;Solid;Standardization;targeted treatment;Technology;Testing;Therapeutic;therapy development;Time;Transcranial magnetic stimulation;Treatment outcome;United States National Institutes of Health;Work

PROJECT_TITLE: Emotional Cognition: Establishing Constructs and Neural-Behavioral Mechanisms in Older Adults with Depression (ENSURE)

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: DURHAM

ORG_DEPT: GENETICS

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: NARRATIVE  The goal of this proposal is to elucidate calcineurin-signaling cascades governing stress responses and virulence of the human fungal pathogen Cryptococcus, which has a significant global public health impact and infects both immunocompromised (HIV/AIDS, transplant recipients, and others) and immunocompetent individuals to cause life-threatening diseases of the lungs and brain (pneumonia, meningoencephalitis). Combined, Cryptococcus species are responsible for >220,000 infections each year and more than 181,000 deaths worldwide, resulting in >15% of all HIV/AIDS-associated deaths. The studies proposed will 1) identify and characterize novel calcineurin-interacting proteins and study these as short- and long-term effectors of stress-responsive virulence pathways, and 2) define the roles of calcineurin re-localization to P-bodies/stress granules during stress in operating a bifurcated stress-response pathway required for pathogenesis.

PI_NAMEs: HEITMAN, JOSEPH  (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: analog;Animal Disease Models;anti-fungal agents;Aspergillus;biological adaptation to stress;Body Temperature;Brain Diseases;Calcineurin;Calcineurin inhibitor;calcineurin phosphatase;Calcium;Calmodulin;Candida;Cations;Cell Survival;Cell Wall;Cellular biology;Cellular Stress;Cessation of life;ChIP-seq;chromatin immunoprecipitation;Cryptococcus;Cryptococcus neoformans;Cytoplasm;Data;data integration;Disease;effective therapy;Eukaryota;Event;experimental study;extracellular;Gene Expression;Genes;Genetic;Genetic Transcription;Genomics;Goals;Growth;Heat Stress;High temperature of physical object;HIV/AIDS;Human;Immunocompetent;Immunocompromised Host;Immunosuppressive Agents;In Vitro;Individual;Infection;Label;Leishmania;Life;Location;Lung Diseases;Mediating;Meningoencephalitis;Messenger RNA;Modeling;Molecular;Mucor;Mutagenesis;mutant;Mutation;Mycoses;novel;Nuclear;Operon;Orthologous Gene;pathogen;Pathogenesis;pathogenic fungus;pathogenic microbe;Pathway interactions;Patients;Phenotype;phosphoproteomics;Phosphoric Monoester Hydrolases;Phosphorylation;Plants;Plasmodium;Play;Pneumonia;Post-Transcriptional Regulation;posttranscriptional;PPP3CA gene;Process;Protein phosphatase;Proteins;Proteomics;Public Health;Regulon;Resistance;response;ribosome profiling;RNA;RNA Binding;RNA-Binding Proteins;Role;Seminal;Series;Serine;Signal Transduction;Site;Stress;stress granule;targeted treatment;Techniques;Temperature;Tertiary Protein Structure;Testing;therapeutic target;Threonine;Time;transcription factor;Transcriptional Regulation;transcriptome sequencing;Translational Regulation;Translations;Transplant Recipients;Virulence;Virulence Factors

PROJECT_TITLE: Calcineurin signaling cascades governing Cryptococcus virulence

STUDY_SECTION: HCAC

STUDY_SECTION_NAME: HIV Coinfections and HIV Associated Cancers Study Section[HCAC]


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

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: PROJECT NARRATIVE Serine deprivation is a promising therapeutic approach in cancer, but dietary serine starvation may be difficult to achieve in humans. Here, we present a novel therapeutic serine-degrading enzyme that can reduce circulating serine levels by greater than 90% in the absence of dietary changes. In this proposal we will further characterize enzymatic serine degradation as a potential therapeutic option in multiple tumor types, including luminal breast tumors which are auxotrophic for serine and therefore highly sensitive to serine depletion therapy.

PI_NAMEs: COLOFF, JONATHAN L.;STONE, EVERETT  (contact)

PROGRAM_OFFICER_NAME: HARRIS, RAYMOND D

PROJECT_TERMS: Acute Lymphocytic Leukemia;addiction;Amino Acids;Anabolism;asparaginase;Asparagine;auxotrophy;Biodistribution;cancer cell;Cancer Patient;cancer therapy;cell type;Chemistry;Circulation;Clinical;clinical development;Consumption;cytokine;Data;deprivation;Development;Diet;Diet Modification;dietary;Disease;effective therapy;efficacy evaluation;Engineering;Enzymes;Estrogen receptor positive;experimental study;extracellular;Goals;Growth;high throughput screening;Human;Human Engineering;Hydro-Lyases;Immune;Immune system;improved;in vivo;interest;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Mediating;Metabolism;Methods;Modality;Modeling;mouse model;Mus;Mutation;Myeloid-derived suppressor cells;Neurologic;novel therapeutics;Nutrient;Outcome;Pathway interactions;Patient Compliance;Patients;Pegaspargase;Pharmacodynamics;pharmacologic;Physiological;Positioning Attribute;Pre-Clinical Model;Property;Protein Engineering;Proteins;prototype;Role;Route;Serine;Serum;side effect;standard of care;Starvation;Structure;success;synergism;Synthetic Diet;T-Lymphocyte;targeted treatment;Testing;Therapeutic;Therapeutic Agents;therapeutic enzyme;therapeutically effective;Treatment Efficacy;tumor;tumor growth;Tumor Immunity;tumor metabolism;Tumor-associated macrophages

PROJECT_TITLE: Therapeutic enzyme depletion of L-serine for cancer treatment

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


ORG_CITY: Aurora

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Pediatric polypharmacy (defined as ≥5 concurrent medications) is a major public health problem with high prevalence among the priority population of children with medical complexity. Pediatric polypharmacy is necessary for symptom and disease management, but major opportunities exist to improve outpatient medication management, safety, and value. We will conduct a hybrid type 2 randomized controlled trial to study the effectiveness of a structured pharmacist-led Pediatric Medication Therapy Management (pMTM) intervention on improving the proactive management of polypharmacy by reducing medication-related problems (MRPs), with an evaluation guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to determine whether pMTM could be transformational for optimizing polypharmacy among children with medical complexity.

PI_NAMEs: FEINSTEIN, JAMES A (contact)

PROJECT_TITLE: Optimizing the Clinical Management of Polypharmacy for Children with Medical Complexity