PROJECT_TERMS: Address;Affect;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid;Amyloid beta-Protein;amyloid pathology;Anesthesia procedures;Animals;Astrocytes;Attention;Autopsy;awake;barrel cortex;Biochemical;Biological Markers;Biostatistics Core;Blood flow;Blood Vessels;Brain;calmodulin-dependent protein kinase II;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;cerebrovascular pathology;Collaborations;comorbidity;Consultations;Data;data management;Dementia;disease model;Electrophysiology (science);Endothelial Cells;Enterobacteria phage P1 Cre recombinase;Enzymes;excitotoxicity;extracellular;Functional disorder;functional outcomes;Genes;Glucose;Glucose Transporter;Glutamate Transporter;Glutamates;hippocampal sclerosis;Human;human tissue;Hyperhomocysteinemia;Image;Impairment;In Situ;Individual;Insulin Receptor;Intervention;knock-down;Knowledge;Lactate Transporter;loss of function;Magnetic Resonance Imaging;Measures;Metabolic;Metabolic dysfunction;Metabolism;Microelectrodes;Microvascular Dysfunction;MMP9 gene;Modeling;mouse model;Mus;Names;network dysfunction;neural network;neuroinflammation;Neurons;neurotoxicity;neurovascular coupling;neurovascular unit;novel therapeutic intervention;Outcome Assessment;overexpression;Pathology;Pathway interactions;Phenotype;prevent;Production;Property;Proteins;Receptor Signaling;Rest;restoration;Role;Signal Transduction;Slice;Synapses;synaptic function;Synaptic plasticity;Testing;Tissues;two-photon;vascular cognitive impairment and dementia;vector;Vibrissae;Work

PROJECT_TITLE: Project 3 - Astrocytic glutamate dysregulation in AD and VCID


ADMINISTERING_IC: AG

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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;Cerebrovascular;Dementia;Genetics;Neurodegenerative;Neurosciences

ORG_CITY: LEXINGTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PI_NAMEs: NELSON, PETER T. (contact)

PROJECT_TERMS: Agonist;Alzheimer's Disease;Alzheimer's disease related dementia;Animal Model;Animals;Astrocytes;Astrocytosis;Automobile Driving;Autopsy;Binding;biological adaptation to stress;Blood flow;Blood Vessels;Brain;Brain Hypoxia;brain metabolism;Calcium;cell type;cerebrovascular;Cerebrovascular Circulation;Cerebrum;Clinical;Collaborations;CRSP3 gene;Data;data management;Dementia;Disease;disorder control;Dose;drinking water;EEF1A2 gene;Elderly;Electrophysiology (science);Evaluation;follow up assessment;Functional disorder;Gene Expression;Genes;genetic variant;Genetic Variation;Genotype;gliovascular;Glutamates;Goals;hippocampal cell loss;hippocampal sclerosis;Human;Image;Immunohistochemistry;Impairment;improved;in vivo;Ischemic Preconditioning;Knowledge;limbic-predominant age-related TDP-43 encephalopathy;Link;Magnetic Resonance Imaging;Measures;member;Memory impairment;Messenger RNA;Metabolic;Methods;Microscopy;Modeling;Morphology;mouse model;multi-photon;multidisciplinary;Mus;Nerve Degeneration;neurobehavioral;neurobehavioral test;Neurons;neuropathology;neurovascular;neurovascular coupling;Nicorandil;novel;novel therapeutic intervention;Oral;Outcome;Outcome Assessment;Pathologic;Pathology;Persons;Pharmaceutical Preparations;pharmacologic;Physiology;Play;Potassium Channel;Preparation;prevent;protein TDP-43;Proteins;Public Health;Reporting;Research;Resources;Risk;RNA Splicing;Role;Sampling;sensor;Signal Transduction;single-cell RNA sequencing;skills;Slice;Stress;sulfonylurea receptor;Testing;Transcript;transcriptome sequencing;two-photon;Up-Regulation;uptake;Western Blotting

PROJECT_TITLE: Project 4 - Astrocytic KATP channels in LATE+HS


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Pediatric;Sleep Research

ORG_CITY: CHICAGO

ORG_DEPT: OTHER CLINICAL SCIENCES

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

ORG_STATE: IL

PI_NAMEs: CROWLEY MCWILLIAM, STEPHANIE  (contact)

PROGRAM_OFFICER_NAME: BAIZER, LAWRENCE

PROJECT_TITLE: Adolescent circadian phase shifts: novel time-of-day targets for bright light

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Precision Medicine;Women's Health Research

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: PROJECT NARRATIVE: Breast cancer is the leading cause of cancer mortality in women world-wide. The goal of this proposal is to understand intratumor heterogeneity, a major driver of tumor progression and therapeutic failure responsible for patient deaths, by applying multidisciplinary approaches in experimental and clinical breast cancer. I expect that the new insights gained will lead to new, more effective individualized treatment strategies.

PI_NAMEs: POLYAK, KORNELIA  (contact)

PROGRAM_OFFICER_NAME: KAI, MIHOKO

PROJECT_TERMS: Age;Area;Breast Cancer Patient;cancer cell;Cancer Etiology;cancer heterogeneity;Cells;Cessation of life;Clinical;Clinical Management;clinical practice;Combined Modality Therapy;computerized tools;design;Development;Disease;Disease Progression;Ecosystem;Environment;Enzymes;Epigenetic Process;ERBB2 gene;Evolution;Experimental Models;Failure;follow-up;Genetic;Genetic Transcription;genomic tools;Goals;Heterogeneity;host neoplasm interaction;Immune;Immunotherapy;improved;individualized medicine;insight;Integration Host Factors;interdisciplinary approach;Knowledge;Laboratories;Link;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Metabolic;Neoplasm Metastasis;novel;novel therapeutic intervention;Obesity;patient responsibilities;Patient-Focused Outcomes;Patients;Research;Resistance;stressor;synergism;synthetic lethal interaction;targeted treatment;Testing;Therapeutic;therapy resistant;treatment response;treatment strategy;tumor;tumor heterogeneity;tumor microenvironment;tumor progression;Women's mortality;Work

PROJECT_TITLE: Targeting intratumor heterogeneity in breast cancer


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

ORG_CITY: SAN FRANCISCO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: NARRATIVE Sarcoidosis is a systemic inflammatory disease with an unknown cause or cure that most commonly affects the lungs, but it can also affect almost any other organ. A significant obstacle to successfully managing sarcoidosis patients is our inability to identify individual patients at greater risk for poor disease outcomes. By investigating immune cells and signaling proteins related to sarcoidosis inflammation, I hope to 1) determine their immunologic properties, and 2) understand their potential as biologic markers for clinical outcomes in the disease.

PI_NAMEs: ARGER, NICHOLAS KOSTANDINOS (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: Affect;Antigens;Award;Biologic Characteristic;Biological;Biological Markers;Biology;biomarker validation;Biometry;Blood;Bronchoalveolar Lavage;career development;CD4 Positive T Lymphocytes;cell motility;Cell Separation;Cells;Cellular Assay;Cellular biology;chemokine;Chronic;Chronic Disease;Clinical;Clinical Data;Clinical Research;cohort;CXCL10 gene;CXCL11 gene;CXCL9 gene;cytokine;Data;Development Plans;Disease;Disease Marker;Disease Outcome;Enrollment;Epidemiology;Etiology;experience;Eye;Flow Cytometry;follow-up;Funding;Goals;Grant;Granuloma;Granulomatous;Granulomatous disease;Heart;Helper-Inducer T-Lymphocyte;Immune;Immunologics;Immunology;in vitro Assay;Incidence;individual patient;Infiltration;Inflammation;Inflammatory;interest;Interferon Type II;Interferons;Kidney;Life;Light;Link;Liver;Longitudinal cohort;Lung;Lung Diseases;Measures;Memory;Mentored Patient-Oriented Research Career Development Award;Mentors;Modeling;Monitor;Morbidity - disease rate;mortality;Natural History;Nervous System;Newly Diagnosed;Newly Diagnosed Disease;novel;Organ;Outcome;Pathogenicity;Patients;Pattern;Phenotype;Population;Production;Property;Proteins;Publications;pulmonary function;Pulmonary function tests;Research;Research Methodology;response;Risk;Running;Sarcoidosis;Serum;Severities;Severity of illness;Signaling Protein;Site;skills;Skin;Source;Spleen;statistics;Surface;T memory cell;T-bet protein;T-Lymphocyte;Testing;Therapeutic immunosuppression;Time;time use;Tissues;tool;Toxic effect;Training;Training Activity;translational scientist;Visit

PROJECT_TITLE: Using high T-bet-expressing cells and Serum Chemokines as Indicators of Disease Severity in Sarcoidosis

STUDY_SECTION: MPOR

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


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Cancer;Genetics;Lung;Lung Cancer;Prevention;Rare Diseases;Tobacco;Tobacco Smoke and Health

ORG_CITY: HOUSTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: PROJECT NARRATIVE Lung adenocarcinoma (LUAD) with genetic alterations in the KRAS oncogene is the most common lung cancer diagnosed in smokers, and strategies to intercept this ominous malignancy heavily rest on understanding the earliest events in its development. While it is understood that tobacco carcinogen exposure results in widespread injury in the lung in the form of molecular and inflammatory changes that commence in visually normal cells, we still poorly understand how KRAS-mutant LUAD is conceived from the tobacco-exposed lung. This project will discern how a unique population of lung cells that arise following tobacco exposure evolve to premalignancy and KRAS-mutant LUAD, discern mechanisms that promote their oncogenic progression, as well as identify drugs that can target these cells and prevent development of KRAS-mutant LUAD.

PI_NAMEs: KADARA, HUMAM  (contact);MOGHADDAM, SEYED JAVAD MIRHASSANI

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone;Ablation;Address;Air;Alveolar Cell;biomarker identification;cancer diagnosis;Carcinogen exposure;Carcinogens;Cell Communication;cell type;Cells;checkpoint inhibition;Chronic Obstructive Pulmonary Disease;cytokine;Data;Development;Disease;Drug Screening;Early treatment;Ecosystem;Epithelium;Event;Evolution;Exhibits;Exposure to;Foundations;Growth;high-throughput drug screening;Human;human tissue;Immune;Immunity;improved;Inflammation;Inflammatory;Inflammatory Response;Injury;insight;Intercept;Interleukin-1 beta;Knowledge;KRAS2 gene;Lesion;Liquid substance;Lung;Lung Adenocarcinoma;lung development;Lung Neoplasms;Macrophage;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Molecular;molecular subtypes;mouse model;multidisciplinary;Mus;mutant;Mutation;Neoplasms;neoplastic cell;Nontypable Haemophilus influenza;Normal Cell;novel;novel strategies;Oncogenes;Oncogenic;Organoids;Pathologic;Patients;Pattern;Pharmaceutical Preparations;Phenotype;Population;premalignant;prevent;Prevention strategy;Process;progenitor;Prognosis;programs;Property;Public Health;receptor;Reporter;Resolution;Rest;Risk;Role;Saline;screening;Signal Transduction;single-cell RNA sequencing;Smoker;Smoking;Somatic Mutation;Specimen;Structure of parenchyma of lung;Tobacco;tobacco exposure;Tobacco-Associated Carcinogen;TP53 gene;transcriptomics;treatment strategy;tumor;tumor initiation;tumorigenesis;Visual

PROJECT_TITLE: Elucidating the evolution of Krt8+ alveolar cells to Kras-mutant lung preneoplasia and cancer

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE This Training Program will provide support for MD and PhD trainees to work with a collaborative group of senior scientists, conducting medically-relevant research to address important questions in pulmonary and critical care medicine. Through a combination of a mentored research experience and select graduate-level courses, trainees will be prepared to pursue the new biology of pulmonary and critical care medicine for the future, working as part of collaborative teams linking basic and clinic research to bring new discoveries to the care of patients.

PI_NAMEs: PAINE, ROBERT  (contact)

PROGRAM_OFFICER_NAME: KALANTARI, ROYA

PROJECT_TITLE: Multidisciplinary Pulmonary and Critical Care Training Program

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM(JA)]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

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

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Contraception/Reproduction;Genetics;Infertility;Polycystic Ovary Syndrome (PCOS);Women's Health Research

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: Project Narrative Female infertility due to disorders of androgen imbalance, namely polycystic ovary syndrome and ovarian insufficiency, are a growing public health problem in the U.S. and worldwide. This project aims to delineate the mechanisms of androgen actions in the ovary, focusing on novel non-coding RNA regulation by androgen receptor in granulosa cells and the role of cytoplasmic adaptor protein paxillin. The training plan is designed to groom a young physician-scientist for an independent career in reproductive science, and the findings will advance our understanding of the molecular mechanisms underlying female fertility.

PI_NAMEs: ASTAPOVA, OLGA  (contact)

PROGRAM_OFFICER_NAME: TAYMANS, SUSAN

PROJECT_TERMS: Adaptor Signaling Protein;Advisory Committees;Affect;androgen excess;Androgen Receptor;Androgens;Anovulation;Apoptosis;Apoptotic;Biology;career;career development;Cell Proliferation;Cells;Chronic;collaborative environment;Communities;cost;Cytoplasm;Data;design;Development;diminished ovarian reserve;Disease;Doctor of Philosophy;Enterobacteria phage P1 Cre recombinase;Equilibrium;Estrous Cycle;Failure;Female;female fertility;Female infertility;Fertility;Follicular Atresia;folliculogenesis;follow-up;Gene Targeting;Genetic Transcription;graduate student;Grant;granulosa cell;Grooming;Growth;Hormone imbalance;Hour;Human;improved;Infertility;inhibitor;Instruction;interest;knock-down;Knock-out;Knockout Mice;Laboratories;Leadership;Ligands;Litter Size;male fertility;Malignant neoplasm of prostate;Mediating;Mediator;meetings;member;Mentors;Messenger RNA;MicroRNAs;miRNA expression profiling;Molecular;mouse genetics;mouse model;mRNA Expression;mRNA sequencing;Mullerian-inhibiting substance receptor;multicatalytic endopeptidase complex;Mus;mutant;novel;novel therapeutics;Nuclear Translocation;Ovarian;Ovarian Follicle;Ovarian hormone;Ovary;Ovulation;Pathway interactions;Patients;paxillin;Phenotype;Physicians;Pilot Projects;Polycystic Ovary Syndrome;Post-Transcriptional Regulation;promoter;protein degradation;Protein Synthesis Inhibition;Proteins;Psyche structure;Public Health;Publications;Qualifying;receptor expression;Regulation;Reproduction;reproductive;Reproductive Sciences;Research;Research Methodology;Research Personnel;Research Technics;Role;Running;Scientist;Signal Transduction;small molecule;Small RNA;stem;Steroids;Supplementation;Technical Expertise;therapeutic candidate;Time;Training;transcriptome;Translational Research;Translations;Universities;Untranslated RNA;Writing

PROJECT_TITLE: Paxillin and Androgens in the Regulation of Ovarian Follicle Development

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Reproduction, Andrology, and Gynecology Study Section[CHHD-R]


NIH_SPENDING_CATS: Cancer;Cervical Cancer;Clinical Research;Clinical Trials and Supportive Activities;Infectious Diseases;Prevention;Sexually Transmitted Infections;Topical Microbicides;Women's Health Research

ORG_CITY: CINCINNATI

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: Project Narrative The elimination of cervical cancer as a public health disease requires the adoption and implementation of strategies that are easily accessible, affordable, acceptable and are equally efficacious in women living with HIV. Hence, we will study the safety and acceptability of a novel formulation of a combination protease inhibitor (Lopinavir/Ritonavir) developed as a self- administered vaginal capsule for use as treatment or an adjunct to treatment for women who screen VIA positive, a surrogate for cervical precancer. Additionally, we seek to establish pilot efficacy data in support of implementing a large-scale clinical trial of this innovative approach to secondary cervical cancer prevention.

PI_NAMEs: PINDER, LEEYA F (contact)

PROGRAM_OFFICER_NAME: SAHASRABUDDHE, VIKRANT V

PROJECT_TERMS: Ablation;Acetic Acids;Address;Adopted;Adoption;Adverse event;Africa South of the Sahara;anti-cancer;antiretroviral therapy;arm;Atopobium vaginae;Behavioral;Biological Assay;Biological Factors;Cancer Etiology;Cancerous;capsule;Cervical;cervical cancer prevention;Cervical Cancer Screening;Cervical Intraepithelial Neoplasia;cervicovaginal;Cervix Uteri;chronic infection;Clinic;Clinical Trials;cohort;Cold Therapy;Conventional Surgery;cytokine;Cytology;Data;Disease;Electrosurgery;Eligibility Determination;Enrollment;Environmental Risk Factor;Epithelium;Excision;Exudate;Formulation;Freezing;Gel;Generations;Goals;HIV;HPV-High Risk;Human papilloma virus infection;Human Papillomavirus;In Vitro;innovation;Interferon Type II;Interleukin-10;Interleukin-2;Interleukin-4;Interleukin-6;Intervention;Interview;Intravaginal Administration;Investigation;Kenya;Lopinavir/Ritonavir;low and middle-income countries;Malignant neoplasm of cervix uteri;Methods;multiplex assay;novel;Outcome;Participant;Pattern;Persons;Phase;Placebos;premalignant;Protease Inhibitor;Public Health;Questionnaires;Randomized;Randomized, Controlled Trials;Recommendation;Research;response;safety assessment;safety study;scale up;screening;Secondary to;Self Administration;Signal Transduction;social;standard of care;Structure;Surveys;Techniques;Telephone;Testing;Therapeutic;Therapeutic Agents;Thermal Ablation Therapy;Time;TNF gene;Transforming Growth Factor beta;treatment as usual;treatment comparison;Treatment outcome;treatment response;treatment strategy;trend;tumor-immune system interactions;Vagina;Vaginal Route of Drug Administration;Visit;Visual;Woman;Women's mortality;women's treatment;Women's trial;Work;Zambia

PROJECT_TITLE: RepurPosed AntiretrOviraL ThErapieS to EliminAte Cervical Cancer (POLESA Trial)


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Heart Disease;Hematology;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: INDIANAPOLIS

ORG_DEPT: GENETICS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Clonal hematopoiesis of indeterminate potential (CHIP) is a novel, asymptomatic condition that predisposes to the development both leukemia and cardiovascular disease; however, while CHIP appears to be quite common, the mechanisms underlying its pathogenesis are not well understood. This study will investigate the contributions of inflammatory pathways and hematopoietic lineages to CHIP-associated cardiovascular disease and their potential as therapeutic targets. The development of innovative therapies targeting these pathways may enable the treatment of established CHIP-associated cardiovascular disease, which would significantly improve the clinical outcomes of patients with CHIP.

PI_NAMEs: BURNS, SARAH S (contact)

PROGRAM_OFFICER_NAME: CHEON, YEWON

PROJECT_TERMS: Acceleration;Adaptor Signaling Protein;Address;age related;Aging;Arterial Fatty Streak;Atherosclerosis;Blood Cells;Blood Platelets;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular Manifestation;Cell Lineage;cell type;Cells;Clinical;clinical care;Complex;Coronary heart disease;cytokine;Development;Dioxygenases;Disease Progression;early onset;Epigenetic Process;Evaluation;Exhibits;Fellowship;Flow Cytometry;Genes;Genetic;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Heterogeneity;Immune;improved;Individual;Inflammation;Inflammatory;Inflammatory Response;innovation;Innovative Therapy;Interleukin-1;Interleukin-1 beta;Interleukin-6;Investigation;leukemia;Macrophage;mast cell;Mediating;Medical;Monitor;monocyte;mortality;Mus;Mutate;Mutation;Myelogenous;Myeloid Cells;Myocardial Infarction;Nature;novel;novel therapeutics;Onset of illness;Pathogenesis;Pathology;Pathway interactions;Patient Care;Patient-Focused Outcomes;Patients;pharmacologic;Play;Population;Preleukemia;prevent;Process;Receptor Signaling;Risk;Role;screening;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Somatic Mutation;stem cell differentiation;T-Lymphocyte;targeted treatment;Techniques;Tetanus Helper Peptide;therapeutic development;therapeutic target;Toll-like receptors;transcription factor;treatment response;ultrasound

PROJECT_TITLE: Inflammatory contributions of clonal hematopoiesis to cardiovascular disease


NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics;Hematology;Lymphatic Research;Lymphoma;Orphan Drug;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: WISTAR INSTITUTE

ORG_STATE: PA

PHR: Narrative The tumor suppressor p53 is essential in the prevention of human cancers, and its loss of function leads to tumor initiation and progression. Half of all human cancers have inactivated p53 by mutation or deletion, which results in aberrant aggressive growth. Our proposal focuses on the development of novel Mdm2 degraders to activate p53-independent activities of Mdm2 as an improved therapeutic approach against these aggressive tumors.

PI_NAMEs: EISCHEN, CHRISTINE M.;SALVINO, JOSEPH M (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: 26S proteasome;Address;Affinity;Apoptosis;Apoptotic;Binding;biophysical analysis;cancer cell;cancer survival;Cell Aging;Cell Cycle Arrest;Cells;Cellular Stress;Chemical Structure;clinical efficacy;Data;design;Development;DNA;DNA Damage;drug discovery;Drug Kinetics;Drug Targeting;efficacy evaluation;efficacy study;Evaluation;Family member;Feedback;Genetic Transcription;Goals;Growth;Human;Hydrophobicity;improved;In Vitro;in vivo;in vivo Model;inhibitor;Lead;lead optimization;Ligands;loss of function;Lymphoma;Malignant Neoplasms;MDM2 gene;Mediating;Metabolic;mimicry;Mus;mutant;Mutate;Mutation;N-terminal;Neutropenia;novel;Oncogenes;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phase III Clinical Trials;pre-clinical;Prevention;Property;Protac;protein degradation;Proteins;Proteomics;Repair Complex;Reporting;research clinical testing;Resistance;Role;Safety;Sarcoma;screening;Series;Signal Transduction;Site;Stress;Testing;Therapeutic;Thrombocytopenia;Toxic effect;TP53 gene;Transactivation;transcription factor;tumor;Tumor Burden;tumor initiation;tumor progression;tumorigenic;ubiquitin-protein ligase;Validation;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Design of the First Mdm2 Targeting PROTACs for treatment of p53 Mutant or Deficient Cancers

STUDY_SECTION: DMP

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Lung;Lung Cancer;Pediatric;Pediatric Cancer;Rare Diseases

ORG_DEPT: PEDIATRICS

PHR: Project Narrative This R50 NCI Research Specialist Award will support my ongoing and new bioinformatic developments and utilization within the context of the following three NCI-funded projects. (1) Development of Advanced Preclinical Models for Pediatric Solid Tumors (R01CA243555), (2) Development of Novel Protein-based Therapeutics for Lung Cancer (R01CA225103), (3) Role of Long Non-coding RNAs in Sarcoma Pathogenesis (R01CA211657). Software/data sources generated from these projects will be published and integrated into other computational workflows and released to the wider public.

PI_NAMEs: LEE, ALEX  (contact)

PROGRAM_OFFICER_NAME: GRIL, BRUNILDE M

PROJECT_TERMS: Adult;Advanced Development;anti-cancer research;ATAC-seq;Award;Bioinformatics;Biology;Cancer Biology;career;Cell Line;Childhood;Childhood Solid Neoplasm;chromatin isolation by RNA purification sequencing;chromatin remodeling;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Communities;computational pipelines;Computer software;computerized tools;Data Sources;Development;Drug resistance;Drug Targeting;Engineering;Enhancers;Ewings sarcoma;Funding;Genetic Transcription;Goals;Grant;high throughput analysis;Immune checkpoint inhibitor;In Vitro;in vivo Model;insight;Laboratories;Malignant neoplasm of lung;Manuscripts;Mediating;member;Mentors;Molecular;multiple omics;novel;Outcome;Pathogenesis;patient derived xenograft model;Patients;Pre-Clinical Model;programmed cell death ligand 1;Proteins;Publishing;receptor;Repression;Research;Role;Sarcoma;single-cell RNA sequencing;Site;software development;Solid Neoplasm;Specialist;Technology;Testing;Therapeutic;Tissues;tumor progression;Untranslated RNA

PROJECT_TITLE: Utilizing Multi-omics to Facilitate Cancer Biology Research


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Biotechnology;Duchenne/ Becker Muscular Dystrophy;Muscular Dystrophy;Orphan Drug;Pediatric;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Transplantation

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative There has been tremendous excitement for the therapeutic potential of iPS cells in treating genetic diseases. The intent of this grant is to perform preclinical studies with cGMP-compatible pluripotent stem cell-derived myogenic progenitors in nonhuman primates (NHPs) as well as to determine for the first time the impact of HLA mismatch in muscle engraftment through the transplantation of allogeneic and autologous cells using the NHP system. This cell therapy has the potential to provide long-term therapeutic effect in DMD, as well as other devastating types of muscular dystrophies.

PI_NAMEs: GRAHAM, MELANIE LYNN;PERLINGEIRO, RITA C. R. (contact)

PROGRAM_OFFICER_NAME: CARIFI, EMILY FORAN

PROJECT_TERMS: Address;Adverse event;Alleles;Allogenic;Animal Model;Autologous;Biochemical;Biodistribution;Biological Assay;Cell membrane;Cell Therapy;Cell Transplantation;cell type;Cells;Cessation of life;Chronic;Clinical;clinical application;clinical translation;cohort;Collaborations;Companions;Complex;Consultations;Cyclic GMP;Defect;Disease;Disparate;Dose;Duchenne muscular dystrophy;Dystrophin;effective therapy;Engraftment;Environment;experimental study;first-in-human;Future;Generations;Genetic;Genetic Diseases;Glycoproteins;Goals;Grant;Homologous Transplantation;Human;human induced pluripotent stem cells;immunosuppressed;Immunosuppression;Impairment;induced pluripotent stem cell;injured;Injury;Investigational Drugs;Knowledge;Laboratories;Lead;manufacture;manufacturing cost;Methods;MHC Class I Genes;MHC Class II Genes;Minnesota;Modeling;Mononuclear;Movement;Mus;Muscle;Muscle Cells;Muscle Fibers;muscle progenitor cell;muscle regeneration;Muscle satellite cell;Muscular Dystrophies;Myopathy;nonhuman primate;Outcome Measure;Patients;Phase;Physiological;Pluripotent Stem Cells;Positioning Attribute;pre-clinical research;preclinical study;primary outcome;progenitor;programs;proliferation potential;Protocols documentation;Regenerative Medicine;Research;Research Personnel;response;Route;Safety;skeletal;Skeletal Muscle;stem cell therapy;Surgeon;System;Technology;Therapeutic;Therapeutic Effect;Time;tissue degeneration;Transplantation;United States Food and Drug Administration;United States National Institutes of Health;Universities;virtual;Xenograft procedure

PROJECT_TITLE: Preclinical studies of pluripotent stem cell-derived myogenic progenitors in non-human primates

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Genetics;Hematology;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Revised Project Narrative This work may identify the genetic basis for the predisposition to acquire myeloproliferative neoplasm as well as develop a screening tool to identify those with this predisposition. This population at risk could then be targeted for preventative studies.

PI_NAMEs: FLEISCHMAN, ANGELA GOFFREDO (contact)

PROGRAM_OFFICER_NAME: ROY, CINDY

PROJECT_TERMS: Acceleration;Acetylcysteine;Affect;Age;aged;Aging;aging population;Agonist;Anti-Inflammatory Agents;Antioxidants;Attention;biobank;Biological Markers;Blood;Bone Marrow;Bone Marrow Stem Cell;Cell Cycle;cell type;Cells;ChIP-seq;Chronic;Clinical Trials;Clonal Hematopoietic Stem Cell;cytokine;Cytokine Receptors;Cytotoxic Chemotherapy;Data;Development;DNA Methylation;DNA sequencing;DNMT3a;Endowment;exhaustion;experimental study;Exposure to;Family;Family history of;Family member;Family-Based Registry;fitness;Gene Expression;Gene Expression Profiling;Genes;Genetic;Hematologic Neoplasms;Hematology;Hematopoiesis;Hematopoietic;hematopoietic stem cell emergence;hematopoietic stem cell quiescence;Hematopoietic stem cells;Human;Inflammation;Inflammatory;Interleukin-10;Ligands;Link;Lipopolysaccharides;Malignant - descriptor;member;Methylation;methylation pattern;Modeling;monocyte;mosaic;Mus;mutant;Mutation;Myeloproliferative disease;Oxidative Stress;Pathway interactions;Patients;peripheral blood;Persons;pharmacologic;Phenotype;Populations at Risk;Predictive Value;Predisposition;preservation;Prevalence;prevent;Prevention trial;Production;progenitor;Proliferating;Reactive Oxygen Species;Recombinant Interleukin-10;Recording of previous events;Regulation;Resistance;response;Role;Screening procedure;Signal Transduction;Sorting;stem;stem cell exhaustion;stem cell function;Stress;stressor;Testing;Therapeutic;TLR4 gene;TNF gene;Toll-like receptors;transcriptome sequencing;Translating;Transplantation;Wild Type Mouse;Work

PROJECT_TITLE: Role of IL-10R signaling in inflammation induced exhaustion of HSC and emergence of JAK2V617F clonal hematopoiesis

STUDY_SECTION: BBHV

STUDY_SECTION_NAME: Basic Biology of Blood, Heart and Vasculature Study Section [BBHV]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Esophageal Cancer;Genetics;Orphan Drug;Rare Diseases

ORG_CITY: CAMDEN

ORG_NAME: CORIELL INSTITUTE FOR MEDICAL RESEARCH

ORG_STATE: NJ

PHR: Esophageal squamous cell carcinoma (ESCC) is prevalent in the world with a 5-year survival rate around 18%. Using human cells and animal models, we will characterize the molecular consequences of NRF2 hyperactivation in ESCC, determine the mechanisms of action and efficacy of NRF2 inhibitors, and find NRF2- responsive kinases and their functions in NRF2-driven ESCC biology. If successful, this work will help develop targeted therapy of NRF2high ESCC in human patients.

PI_NAMEs: CHEN, XIAOXIN LUKE (contact);MAJOR, MICHAEL BENJAMIN

PROGRAM_OFFICER_NAME: YASSIN, RIHAB R

PROJECT_TERMS: 3-Dimensional;advanced disease;Affect;Anabolism;Animal Model;Apoptosis;Architecture;Automobile Driving;Biochemistry;Biological Models;Biology;Cancer Etiology;cancer type;CDKN2A gene;Cell Line;Cell model;Cells;Cellular biology;Cessation of life;Clinic;CUL3 gene;Data;Data Set;design;Development;Diagnosis;differential expression;Drug Metabolic Detoxication;Drug Screening;empowerment;Epithelial Cells;Epithelium;Esophageal Squamous Cell Carcinoma;Esophagus;Event;Experimental Models;experimental study;Expression Profiling;Future;Genes;Genetic;Genetic Transcription;genomic locus;glycosylation;Growth;Human;Hyperactivity;Hyperplasia;In Vitro;in vivo;inhibitor;insight;Lesion;life span;LoxP-flanked allele;Lung;Malignant Epithelial Cell;Malignant neoplasm of lung;Malignant Neoplasms;member;Metabolism;metabolomics;Modeling;Molecular;Multiomic Data;Mus;Mutate;Mutation;Neoplasm Metastasis;new therapeutic target;Normal Cell;novel;novel therapeutics;Oncogenic;Organoids;Pathway interactions;Patients;pharmacologic;Pharmacology;Pharmacology Study;Phase;Phenotype;Phosphotransferases;PI3K/AKT;PIK3CA gene;PIK3CG gene;Preventive;programs;Proliferating;Proteomics;Pyrimethamine;Pyruvate Kinase;Recurrence;Regulation;Reporting;Research;response;Signal Pathway;Signal Transduction;small molecule;small molecule inhibitor;Stains;Stress;Surveys;Survival Rate;synergism;Tamoxifen;targeted treatment;Testing;Therapeutic;Therapeutic Agents;therapeutic evaluation;Tissue Microarray;Tissues;TP53 gene;transcription factor;transcriptome sequencing;Translating;tumor progression;Tumor Promoters;United States;Validation;Work;Xenograft procedure

PROJECT_TITLE: Mechanisms and Targeted Therapy of NRF2-high Esophageal Squamous Cell Carcinoma

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunization;Precision Medicine;Prostate Cancer;Urologic Diseases

ORG_CITY: MADISON

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative There is a critical unmet need for improved models to enable more effective clinical trial design. This proposal will test the utility of a bone marrow tissue chip to identify patients with metastatic castrate resistant prostate cancer most likely to have a response to a candidate new cell- surface targeted therapeutic agent currently in Phase II/III clinical trials.

PI_NAMEs: BEEBE, DAVID J (contact);LANG, JOSHUA MICHAEL

PROGRAM_OFFICER_NAME: MCKEE, TAWNYA C

PROJECT_TERMS: androgen independent prostate cancer;Animal Model;Antibodies;Antibody Therapy;Antibody-drug conjugates;Biopsy;bone;Bone Marrow;Bone Marrow Aspiration;Bone Marrow Neoplasms;cancer cell;Cancer Patient;cancer type;Carcinoma;Cell Death;Cell Proliferation;Cell surface;Cell Therapy;cell type;Cells;chimeric antigen receptor natural killer cells;Clinic;Clinical;Clinical Trials;Clinical Trials Design;Coculture Techniques;Collagen;Complex;Coupled;cytotoxic;Data;design;Disease;Disseminated Malignant Neoplasm;Economics;effective therapy;efficacy clinical trial;Endothelial Cells;Endothelium;Environment;environmental change;Failure;Future;Human Resources;humanized antibody;Hydrogels;Immune;improved;in vitro Model;in vivo;induced pluripotent stem cell;Induction of Apoptosis;innovation;Investments;Malignant Bone Marrow Neoplasm;Malignant Neoplasms;Measures;Mediating;men;Metastatic Neoplasm to the Bone;Modeling;monocyte;multidisciplinary;Neoplasm Metastasis;neoplastic cell;novel therapeutics;Oncology;Osteoblasts;Osteoclasts;Outcome;patient population;patient stratification;Patients;peripheral blood;Pharmaceutical Preparations;Phase;Phase II Clinical Trials;phase II trial;Phase II/III Clinical Trial;phase III trial;Physiology;Play;Positioning Attribute;pre-clinical;predicting response;Prediction of Response to Therapy;Prognosis;Prostatic Neoplasms;receptor;Resistance;Resources;responders and non-responders;response;Role;Sampling;screening;Selection for Treatments;SN-38;Solid Neoplasm;spheroids;Stimulus;Stromal Cells;success;synergism;targeted treatment;Testing;Therapeutic;Therapeutic Agents;therapy development;therapy resistant;Time;Tissue Microarray;tool;Topoisomerase Inhibitors;Topoisomerase-I Inhibitor;Toxic effect;transcriptomics;Treatment Efficacy;Treatment outcome;treatment responders;treatment response;trial design;tumor;tumor growth;tumor microenvironment;Vascularization

PROJECT_TITLE: Mechanisms of microenvironment mediated resistance to cancer cell surface targeted therapeutics


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Bioengineering;Clinical Research;HIV/AIDS;Prevention;Substance Misuse

ORG_CITY: GAINESVILLE

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: NARRATIVE The majority of persons with HIV (PWH) in the US consume alcohol, despite that alcohol use is associated with lower levels of HIV care engagement and HIV viral suppression. The overarching goals of the current grant proposal are to advance understanding of the mechanisms influencing adherence to contemporary HIV therapeutic regimens, and to incorporate alcohol-related interventions into emerging clinic- and community- based strategies to achieve and maintain HIV viral suppression across diverse populations. The rich information we collect in this project will establish a solid foundation for our next step: a hybrid implementation/effectiveness trial of an integrated alcohol intervention across a large network of clinic- /community-based HIV settings in Florida.

PI_NAMEs: COOK, ROBERT L (contact);WANG, YAN

PROGRAM_OFFICER_NAME: FREEMAN, ROBERT

PROJECT_TERMS: absorption;Address;Adherence;Age;Alcohol consumption;alcohol intervention;Alcoholic beverage heavy drinker;Alcohols;Anxiety;Applications Grants;Appointment;Area;Area Under Curve;assessment application;barrier to care;Biosensor;Blood;Caring;Cellular Phone;Clinic;Clinical;cohort;Collaborations;Communities;community setting;community-level factor;Data;design;Development;drinking;Dryness;Ecological momentary assessment;Economics;effectiveness/implementation trial;Enrollment;ethnic minority;Ethnic Origin;Florida;Foundations;Gender;Goals;Health;Health system;Healthcare Systems;HIV;improved;Individual;Intervention;Life;Measures;Mental Depression;Mental Health;mHealth;mhealth interventions;Mission;mobile computing;Modeling;Monitor;multimodality;next generation;Outcome;Pain;Participant;Patient Self-Report;Pattern;peer support;Persons;Pharmaceutical Preparations;Population Heterogeneity;Postdoctoral Fellow;pre-doctoral;programs;Provider;Race;Regimen;Reporting;Research;Research Personnel;Research Support;Risk Factors;rural area;Secure;social;Solid;Spottings;Stress;success;support network;surveillance data;Surveys;syndemic;Technology;Testing;Therapeutic;Time;tool;Training;treatment as prevention;Universities;Viral;Viral Load result;Virginia;Wrist

PROJECT_TITLE: Technology-based assessments and intervention to reduce alcohol consumption and improve HIV viral suppression in the Florida Cohort


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF SOCIAL WELFARE/WORK

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Behavioral and Social Science

ORG_CITY: PORTLAND

ORG_NAME: PORTLAND STATE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Bridges to Baccalaureate in Portland Metro (B2B PDX Metro) will build on past collaborations among Portland Community College, Clackamas Community College, and Portland State University to increase the number of diverse community college students who transfer to four-year universities in biomedical science majors. To achieve this, the investigators will rely on evidence-based approaches, including hands-on learning; research experiences; and an integrated and supportive community of mentors, faculty, and peers at the institutions. This research responds to the Public Health Service Act (Section 304 (242b) by “providing for an expanded and continuing supply of individuals qualified to perform the research, evaluation, and demonstration projects” that contribute to public health.

PI_NAMEs: BLACKWELL, ERNEST ANTAR;KELLER, THOMAS E (contact);LEAVITT, ALISSA

PROGRAM_OFFICER_NAME: STEPANEK, LAURIE ELIZABETH

PROJECT_TERMS: Address;Appointment;Bachelor's Degree;Behavioral Research;Behavioral Sciences;Biomedical Research;bridge to the baccalaureate;career;career development;Clinical Research;cohort;Communities;community college;Credentialing;Data Analyses;Data Collection;Degree Completion;design;Development;Development Plans;Educational Curriculum;Effectiveness;Elements;Ensure;Environment;Evidence based practice;experience;improved;Individual;Institution;interest;Knowledge;Mentors;Mission;Modeling;Outcome;Pathway interactions;Phase;Preparation;Process;programs;recruit;Research;Research Training;scaffold;Science;Scientist;Self Efficacy;skill acquisition;skills;Structure;student mentoring;Students;success;Time;Training;Training Activity;Training Programs;undergraduate student;Underrepresented Populations;Underrepresented Students;Universities

PROJECT_TITLE: Bridges to Baccalaureate Training Program at Portland State University

STUDY_SECTION: TWD

STUDY_SECTION_NAME: Training and Workforce Development Study Section - D[TWD-D]


NIH_SPENDING_CATS: Bioengineering;Data Science;Diabetes;Digestive Diseases;Kidney Disease;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: Project Narrative The Research Educational Program in Computational Autonomic Neurobiology is being developed at the Mayo Clinic in Rochester Minnesota to train a new generation of modern biomedical scientists and physicians capable of performing, interpreting, and applying analyses of increasingly complex and large datasets. By providing participants with foundational knowledge and practical skills to apply computer-based analyses to data from impactful research experiences, the program is poised to advance understanding of diabetes and digestive and kidney diseases.

PI_NAMEs: LINDEN, DAVID R. (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Address;Biomedical Engineering;biomedical scientist;career;Clinic;Clinical;Complex;complex data;computational platform;Computational Science;Computer Analysis;computerized tools;Computers;Computing Methodologies;Data;Data Scientist;Data Set;design;Development;Diabetes Mellitus;Digestive System Disorders;direct application;Disease;Distant;Education;education research;Educational Curriculum;Educational Materials;Educational Models;Ensure;Environment;experience;Faculty;Funding;Future;Generations;graduate student;Health;Human;innovation;Institution;International;Investments;Kidney Diseases;Knowledge;Laboratories;large datasets;Lead;Learning;Medical;Medicine;Mentors;Methods;Minnesota;Modernization;Neurobiology;next generation;open data;Participant;patient engagement;Physicians;Physiological;Physiology;Postdoctoral Fellow;Productivity;Program Evaluation;programs;recruit;Research;Research Project Grants;Resources;Schools;Science;Scientist;skill acquisition;skills;skills training;Training;Training Programs

PROJECT_TITLE: Mayo Clinic Research Education Program in Computational Autonomic Neurobiology of Diabetes and Digestive and Kidney Diseases


ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: PROJECT NARRATIVE  The ability to trace, distinguish, and quantify different oxidation states of the same redox active metal ion (RAMI) simultaneously in vivo is critical in understanding the labile cellular pool, which a fundamental role in diseases arising from homeostatic imbalances. DNAzymes offer a promising method of accomplishing this, but our current gap in knowledge regarding metal ion-DNAzyme interactions precludes our ability to finely tune their sensing capabilities. This work will make significant contributions to healthcare by improving our fundamental understanding of the interactions of DNAzymes with RAMIs, specifically Fe3+, Fe2+, Cu2+, and Cu+, providing the insight necessary to develop these systems into highly sensitive and selective metal ion sensors.

PI_NAMEs: VAN STAPPEN, CASEY MICHAEL (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TERMS: absorption;Affinity;Alzheimer's Disease;analog;Autoradiography;Behavior;Binding;Biochemical;Biological Assay;biomaterial compatibility;Biomedical Research;biophysical properties;Catalysis;Catalytic DNA;Cations;Characteristics;Chemistry;Computer Models;Deoxyribose;design;Detection;Dialysis procedure;Disease;DNA;Electron Spin Resonance Spectroscopy;electronic structure;Employment;Environment;Equilibrium;Foundations;Freezing;functional improvement;Future;geometric structure;Geometry;Goals;Healthcare;High Pressure Liquid Chromatography;high reward;high risk;improved;In Vitro;in vivo;Inductively Coupled Plasma Mass Spectrometry;insight;Investigation;Ions;Isotope Labeling;Kinetics;Knowledge;Ligation;Literature;Location;Metal Binding Site;Metalloproteins;Metals;Methodology;Methods;Modeling;Modification;Molecular;Mossbauer Spectroscopy;Nature;next generation;novel;novel strategies;Oligonucleotides;oxidation;Oxidation-Reduction;Pathology;phosphodiester;Physiologic pulse;Physiological;Point Mutation;Proteins;rational design;Reaction;Research Training;Rest;Risk Factors;RNA;Role;screening;sensor;Series;Site;Solid;spatiotemporal;Specificity;Structure;Structure-Activity Relationship;System;Techniques;Therapeutic;Training;Work

PROJECT_TITLE: Spectroscopic and Mechanistic Characterization of Novel DNAzymes Selective for Redox-active Metal Ions


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

ORG_CITY: Nashville

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE RESEARCH STRATEGY Oligonucleotide agonists of the retinoic acid-inducible gene I (RIG-I) pathway hold significant promise as antiviral agents, vaccine adjuvants, and cancer immunotherapeutics. However, their biological activity and efficacy is limited by poor pharmacological properties, including nuclease degradation, inefficient cellular uptake and cytosolic delivery, and rapid clearance. This proposal aims to address these challenges through the development, optimization, and preclinical evaluation of RIG-I activating nanoparticles (RANs), a platform technology for immunopotentiation via the RIG-I pathway.

PI_NAMEs: PYLE, ANNA MARIE;WILSON, JOHN TANNER (contact)

PROGRAM_OFFICER_NAME: CHEN, JERMONT

PROJECT_TERMS: adaptive immunity;Address;Affinity;Agonist;Anti-viral Agents;antitumor effect;Artificial nanoparticles;Beds;Behavior;Biodistribution;Biological;cancer immunotherapeutics;cancer immunotherapy;Charge;Chemicals;Clinical;clinical application;combinatorial;Cytosol;cytotoxicity;Data;design;Development;Disease;Double-Stranded RNA;Drug Delivery Systems;drug development;Drug Kinetics;efficacy evaluation;Endosomes;Engineering;Foundations;Generations;Genes;Half-Life;Hydrophobicity;immune activation;Immune checkpoint inhibitor;Immune Targeting;Immunobiology;immunogenic;immunogenicity;Immunologics;Immunosuppression;Immunotherapeutic agent;improved;in vivo;in vivo evaluation;Inflammatory;Inflammatory Response;Innate Immune Response;Innate Immune System;innovation;insight;Interdisciplinary Study;Interferon Type I;Investigation;Knowledge;Lead;lead candidate;Length;Libraries;Melanoma;Modality;Modeling;Molecular;mouse model;multidisciplinary;Mus;nanocarrier;nanomedicine;nanoparticle;nanopolymer;Natural Immunity;new technology;next generation;novel;nuclease;Oligonucleotides;Organism;Outcome;Pathway interactions;Pattern recognition receptor;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacologic Substance;Phosphorylation;Polymer Chemistry;Polymers;Positioning Attribute;pre-clinical;preclinical development;preclinical evaluation;Predisposition;prevent;programs;Property;Research;response;RNA;Safety;Science;Site;stem;Structure;synergism;Technology;technology platform;Testing;Therapeutic;therapeutic RNA;Tissues;Toxic effect;Transfection;Translations;Tretinoin;tumor;tumor growth;Tumor Immunity;tumor microenvironment;uptake;Vaccine Adjuvant;Viral;Virus Diseases

PROJECT_TITLE: RIG-I Activating Nanoparticles for Immunopotentiation

STUDY_SECTION: NANO

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: In this project we are proposing comprehensive, highly synergistic, and rigorously controlled studies that will allow to address, directly in vivo, how the size and relative distribution of the HIV reservoir in CD4 T cells and macrophages govern viral persistence on ART, the extent of residual inflammation and neuropathogenesis, as well as viral rebound after ART interruption. We believe our studies will provide critical insights into the mechanisms that govern the cellular and anatomic origins of persisting and rebounding virus. We hope that these insights ultimately will inform the design of novel therapeutic strategies aimed at achieving HIV remission.

PI_NAMEs: ESTES, JACOB D;PAIARDINI, MIRKO  (contact)

PROGRAM_OFFICER_NAME: RAO, VASUDEV RAMACHANDRA

PROJECT_TERMS: Achievement;Acquired Immunodeficiency Syndrome;Address;Adherence;Age;Anatomy;animal resource;antiretroviral therapy;Autopsy;Binding;Biological Markers;Blood;Brain;brain tissue;CCR5 gene;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Central Nervous System;Clinical Trials;clinically relevant;Collection;Controlled Study;cost;Cues;CXCR4 gene;Data;design;detection limit;Development;Disease Progression;Disease remission;DNA;Enrollment;Equilibrium;Fingerprint;Genetic Fingerprintings;Genetic Transcription;Goals;HIV;HIV Infections;In Vitro;in vivo;Individual;Infection;Inflammation;insight;Interruption;Intervention;Kinetics;Life;life span;Location;Macaca mulatta;Macrophage;Mediating;memory CD4 T lymphocyte;Modeling;multidisciplinary;Nature;Neuropathogenesis;novel;novel strategies;novel therapeutic intervention;peer;Persons;Phagocytosis;Predisposition;Primates;Productivity;Recording of previous events;Regimen;Research;Research Personnel;Residual state;Resistance;Rest;Role;side effect;SIV;social stigma;Specimen;success;synergism;T-Cell Depletion;T-Lymphocyte;Time;Tissues;Variant;Viral;viral DNA;Viral Genome;Viral Load result;viral rebound;Viral reservoir;viral RNA;Virion;Virus;Virus Latency;Virus Replication;Work

PROJECT_TITLE: Determining the relative contribution of CD4 T cells and macrophages to HIV persistence and rebound

STUDY_SECTION: HVCD

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


ADMINISTERING_IC: DA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PI_NAMEs: HOWARD, TIMOTHY D;LANGEFELD, CARL D;OLIVIER, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TITLE: Integrated Omics Analysis of Pain: Omics Data Generation Center


NIH_SPENDING_CATS: Chronic Pain;Pain Research;Precision Medicine

PI_NAMEs: OLIVIER, MICHAEL  (contact)

PROJECT_TERMS: Acute;Acute Pain;biomarker identification;biomarker signature;Blood specimen;California;Charge;chronic pain;Clinical;Clinical assessments;clinical center;Clinical Data;clinical research site;Cohort Studies;Collaborations;Communication;Data;data exchange;data integration;data resource;Data Set;Development;Dimensions;Doctor of Philosophy;Ensure;Epigenetic Process;Event;experience;extracellular;Funding;Generations;Genotype;Goals;Health Sciences;Individual;Individual Adjustment;individual patient;Institution;large scale data;Leadership;lipidomics;Mediating;medical schools;metabolomics;Monitor;monocyte;Multiomic Data;multiple omics;musculoskeletal injury;neuroimaging;operation;Operative Surgical Procedures;Pain;pain chronification;Participant;performance site;precision medicine;predictive signature;programs;Proteomics;Psychosocial Assessment and Care;Research Personnel;resilience;RNA;Sampling;Sensory;success;System;Technical Expertise;Testing;timeline;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: Admin-Core

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-ETTN-P]


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Biotechnology;Cancer;Digestive Diseases;Immunization;Immunotherapy;Orphan Drug;Pancreatic Cancer;Rare Diseases;Vaccine Related

ORG_CITY: Charleston

ORG_NAME: LEUKOGENE THERAPEUTICS, INC.

ORG_STATE: SC

PHR: Narrative (Relevance) Pancreatic cancer is one of the deadliest cancers and effective therapies are lacking. We have developed a vaccine-based immunotherapy approach to target the Anterior Gradient-2 (AGR2) protein, which is highly  expressed in pancreatic tumors. Our strategy relies on utilizing AGR2 conjugated to the bacterial superantigen  (SAg) SMEZ-2 that activates a robust anti-AGR2 immune response. We anticipate that these studies will reveal  new ways of treating pancreatic cancer in preclinical models of cancer, setting the stage for clinical development  and the delivery of a new treatment regimen to patients in need.

PI_NAMEs: ROBINSON, REEDER MCNEIL (contact)

PROGRAM_OFFICER_NAME: POND, MONIQUE ADRIANNE

PROJECT_TERMS: Adenocarcinoma;Affinity;Animals;Anterior;anti-cancer;anti-CTLA4 antibodies;anti-PD-1;Antibody titer measurement;Antigen-Presenting Cells;Antigens;B-Lymphocytes;Binding;Biochemistry;Biological Markers;bioluminescence imaging;Blood;Body System;C57BL/6 Mouse;Cancer Model;cancer therapy;Cancer Vaccines;Carrier Proteins;Cell Line;Cells;checkpoint inhibition;chemotherapy;Clinic;clinical candidate;clinical development;Color;Conjugate Vaccines;CTLA4 gene;cytokine release syndrome;Dependence;Detection;Development;Diagnosis;Dose;drug candidate;Drug Metabolic Detoxication;effective therapy;Effector Cell;Enzyme-Linked Immunosorbent Assay;Exotoxins;Family;Firefly Luciferases;Flow Cytometry;Goals;Haemophilus influenzae;Head;Head of pancreas;Histocompatibility Antigens Class II;Histopathology;Human;Immune;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;Immune Targeting;immunogenic;immunogenicity;Immunohistochemistry;Immunologic Markers;Immunologics;Immunophenotyping;Immunosuppression;Immunotherapy;Implant;in vivo;innovation;Interleukin-6;KPC model;Malignant neoplasm of pancreas;Malignant Neoplasms;Maximum Tolerated Dose;Measures;Mediating;member;Modeling;Monitor;mouse model;Mus;mutant;novel;Operative Surgical Procedures;overexpression;Pancreas;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;pancreatic neoplasm;Patient-Focused Outcomes;Patients;Peptide/MHC Complex;Phase;phase 1 study;phase 2 study;pre-clinical;Pre-Clinical Model;programs;Protein Disulfide Isomerase;Proteins;Radiation therapy;receptor binding;Recombinants;Research;response;Schedule;Serum;Streptococcus;Streptococcus pyogenes;subcutaneous;success;Superantigens;Surface;Surrogate Markers;Survival Rate;synergism;T cell response;T-Cell Receptor;T-Lymphocyte;targeted treatment;Testing;theories;Therapeutic;therapeutic vaccine;Tissues;Toxic effect;Toxicology;Treatment Protocols;tumor;Tumor Antigens;tumor growth;Tumor Markers;tumor microenvironment;tumor progression;Tumor-Infiltrating Lymphocytes;tumorigenesis;Vaccinated;Vaccination;vaccine candidate;vaccine development;vaccine immunotherapy;vaccine strategy;Vaccines;Work

PROJECT_TITLE: AGR2-superantigen vaccine conjugate for the treatment of pancreaticductal adenocarcinoma


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Arthritis;Autoimmune Disease;Back Pain;Chronic Pain;Clinical Research;Disability Research;Neurosciences;Osteoarthritis;Pain Research;Physical Injury - Accidents and Adverse Effects

ORG_CITY: PALO ALTO

ORG_NAME: PALO ALTO VETERANS INSTIT FOR RESEARCH

PHR: Project Narrative The studies described in this application use translational mouse models of chronic low back pain and osteoarthritic knee pain, in conjunction with patient serum and tissue samples, to advance our understanding of the adaptive immune changes mediating the transition from tissue injury to chronic localized pain. It is anticipated that these investigations will provide foundational support for future clinical trials utilizing rituximab, avacopan, and other FDA approved treatments for autoimmune diseases. The identification of novel target specific pharmacologic treatments for these chronic musculoskeletal diseases could reduce pain and enhance the quality of life in many patients.

PI_NAMEs: CLARK, DAVID J.;KINGERY, WADE S (contact)

PROGRAM_OFFICER_NAME: GREENWELL, THOMAS

PROJECT_TERMS: adaptive immune response;adaptive immunity;Adrenergic Agents;Antibodies;Antigen-Antibody Complex;Antigens;Arthralgia;Arthritis;Autoantibodies;Autoantigens;Autoimmune;Autoimmune Diseases;Autoimmune Process;Autoimmune Responses;Autoimmunity;B-Lymphocytes;Binding;C5a anaphylatoxin receptor;Calcitonin-Gene Related Peptide Receptor;Cartilage;Cells;Chemical Sympathectomy;Chronic;Chronic disabling pain;Chronic low back pain;chronic pain;Clinical Management;Clinical Trials;Complement;Complement 5a;Complement Activation;Complex Regional Pain Syndromes;cytokine;Cytokine Signaling;Degenerative polyarthritis;Deposition;Dermis;Development;Disabilities experience;disability;economic impact;effective therapy;experimental study;FDA approved;Foundations;Fracture;Functional disorder;Future;Goals;Helper-Inducer T-Lymphocyte;Hindlimb;Immune;Immune response;Immunity;Immunoglobulin Isotypes;Immunoglobulin M;Immunoglobulins;immunoregulation;improved;Inflammatory;Injections;injured;Injury;Innate Immune Response;innovation;Interleukin-6;Intrathecal Injections;Investigation;Iodoacetates;Joints;Knee joint;Knee Osteoarthritis;knee pain;limb fracture;Low Back Pain;lymph nodes;lymphoid organ;Macrophage;Maintenance;Maps;Mediating;Mediator;Microglia;Modeling;Molecular;mouse model;Mus;Musculoskeletal Diseases;Musculoskeletal Pain;Natural Immunity;neoantigens;neural;neural initiation;Neuroimmune;Neurons;Neuropeptides;Nociception;novel;Orthopedics;osteoarthritis pain;Pain;pain chronification;Pain Free;pain patient;pain reduction;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;Plasma;Play;Positioning Attribute;Prevalence;Production;Puncture procedure;Quality of life;Reaction;receptor;response;rituximab;Rodent;Role;Sensory;Serum;Signal Pathway;Signal Transduction;Skin;Spinal;Spinal Cord;spinal disk injury;Structure of germinal center of lymph node;Substance P;System;Testing;tibia;Time;tissue injury;Tissue Sample;tissue trauma;Tissues;Trauma;Wild Type Mouse;Work

PROJECT_TITLE: Neural immunoregulation of post-traumatic autoimmunity

STUDY_SECTION: NPI

STUDY_SECTION_NAME: Neurobiology of Pain and Itch Study Section [NPI]


NIH_SPENDING_CATS: Arthritis;Autoimmune Disease;Biomedical Imaging;Clinical Research;Genetics;Lung;Pulmonary Fibrosis;Rheumatoid Arthritis

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative/Public health relevance: The mortality associated with rheumatoid arthritis associated interstitial lung disease (RA-ILD) is unacceptably high and clinicians are unable to accurately predict prognosis for a disease that is markedly heterogeneous. The overall goal of the proposed research is to identify patients with RA-ILD that are at the highest risk for progressive disease and may potentially benefit from more targeted, and potentially less harmful, treatment. Our proposed research focuses on a critical unmet public health need in RA-ILD by contributing to the fundamental understanding of identification of clinically meaningful disease phenotypes.

PI_NAMEs: LEE, JOYCE SUJIN (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: alveolar epithelium;antifibrotic treatment;Biological Markers;Blood;Cessation of life;Characteristics;chest computed tomography;Clinical;Clinical Trials;Collection;Combined Modality Therapy;comparison control;Country;Data;deep learning;detection sensitivity;Development;Diagnosis;differential expression;Disease;disease diagnosis;disease heterogeneity;disease phenotype;Disease Progression;Epithelial Cells;experience;Exposure to;Fibrosis;fibrotic interstitial lung disease;Foundations;Future;Gene Expression;Genes;genetic risk factor;Goals;Harm Reduction;Health;Heterogeneity;high risk;Histologic;idiopathic pulmonary fibrosis;Image;Imaging technology;Immunosuppression;Individual;ineffective therapies;Interstitial Lung Diseases;Intervention;Investigation;Knowledge;Length;Lung;Lung Diseases;Lung Transplantation;Measures;Methods;Molecular;Morbidity - disease rate;mortality;Natural History;novel;novel therapeutics;Outcome;participant enrollment;Pathway interactions;Patients;Pattern;peripheral blood;Peripheral Blood Mononuclear Cell;Phenotype;Physiological;precision medicine;prevent;Prognosis;Progressive Disease;prospective;proteomic signature;Public Health;public health relevance;pulmonary function;Quality of life;quantitative imaging;radiologist;Radiology Specialty;recruit;Research;Resolution;Rheumatoid Arthritis;risk stratification;Role;Sensitivity and Specificity;standard of care;Structure of parenchyma of lung;Symptom Burden;targeted treatment;telomere;Testing;Time;Tissues;transcriptome;transcriptomics;Transplantation;treatment response;Usual Interstitial Pneumonia;Work

PROJECT_TITLE: Defining the molecular and radiologic phenotype of progressive RA-ILD

STUDY_SECTION: CRD

STUDY_SECTION_NAME: Cardiovascular and Respiratory Diseases Study Section[CRD]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Infectious Diseases;Primary Health Care

ORG_CITY: Newark

ORG_DEPT: DENTISTRY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

PHR: Project Narrative Periodontitis is among the most prevalent causes of years lived with disability among adults worldwide. While antibiotics use may be part of periodontitis treatments based on empirical notions, there are currently no guidelines for periodontal treatment adjunctive antibiotics, which may lead to antibiotic misuse and lack of efficacy. This project will yield reliable clinical and patient-perceived data on the efficacy of periodontal adjunctive antibiotics, which will be translated to evidence-based clinical guidelines for their use only when they are expected to be effective.

PI_NAMEs: KOTSAKIS, GEORGIOS  (contact)

PROGRAM_OFFICER_NAME: FISCHER, DENA

PROJECT_TERMS: Academy;Adult;Adverse event;Affect;aged;American;American Dental Association;Amoxicillin;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;base;Biological;Calibration;Characteristics;Chronic;Classification;Clinical;Clinical Data;clinical practice;Clinical Practice Guideline;Clinical Trials;clinically significant;Combined Antibiotics;Comparative Study;Data;Data Collection;Data Set;Decision Making;Dental;Dental Clinics;Dental General Practice;Dental Offices;Dentistry;Dentists;Dentition;design;Development;Diagnosis;Discipline;Disease;effectiveness evaluation;efficacy evaluation;efficacy outcomes;Enrollment;Evaluation;evidence base;evidence based guidelines;Feasibility Studies;Focus Groups;Goals;Guidelines;Health;Hemorrhage;improved;Individual;Inflammatory;instrument;Investigation;Left;Link;Logistic Regressions;Manuals;Mechanics;Medical;Metronidazole;Modeling;Monitor;Morbidity - disease rate;Nested Case-Control Study;Oral cavity;Participant;pathogenic bacteria;Patient Recruitments;Patients;Pattern;Periodontal Diseases;Periodontal Infection;Periodontitis;Persons;Phase;pilot test;pilot trial;Population;Practice Guidelines;Preparation;prescription document;Procedures;prophylactic;Protocols documentation;Randomized;randomized, clinical trials;Rationalization;recruit;Reporting;Resistance development;resistant strain;response;Sampling Studies;secondary outcome;Shapes;Surveys;System;Tooth Loss;Tooth root structure;Training;Translating;translational potential;Treatment Effectiveness;treatment optimization;treatment response;trial planning;U-Series Cooperative Agreements;Update;Work;years lived with disability

PROJECT_TITLE: Shaping the Indications for Periodontal Adjunctive Antibiotics in Dental Practice: A PBRN Clinical Trial


NIH_SPENDING_CATS: Clinical Research;Data Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: Stellenbosch

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: STELLENBOSCH UNIVERSITY

PHR: PROJECT NARRATIVE Southern Africa faces numerous public health challenges due to the high prevalence of communicable and non- communicable diseases. For this reason, innovative public health research, such as data science (or ‘big data’) approaches, are crucial to promote population health and reduce health inequality. The Research for Ethical Data Science in Southern Africa (REDSSA) project will explore the ethical, legal and social implications of the Harnessing Data Science for Health Discovery and Innovation in Africa (DS-I Africa) initiative by conducting empirical, conceptual and normative research, and developing contextualized evidence-based guidance with the overall aim of enhancing the governance of data science research for health promotion in southern Africa.

PI_NAMEs: MOODLEY, KEYMANTHRI  (contact);RENNIE, STUART

PROGRAM_OFFICER_NAME: CHURCHILL, JAMES D

PROJECT_TERMS: Advisory Committees;Africa;Africa South of the Sahara;African;Artificial Intelligence;Behavioral Research;Big Data;Bioethics;Bioethics Consultants;Biomedical Research;citizen science;cloud storage;Collaborations;commune;Communication;Communities;community engagement;Competence;complex data;computerized data processing;Computing Methodologies;Consensus;Consultations;Country;Creativeness;crowdsourcing;Data;data access;Data Collection;data ecosystem;data exchange;data framework;data literacy;data management;Data Protection;Data Science;Data Set;data sharing;deep learning;Development;Devices;digital;digital data;digital phenotyping;Disease;Education;Empirical Research;empowerment;Ensure;Ethical Analysis;ethical, legal, and social implication;Ethicists;Ethics;Ethics Consultation;evidence base;experience;Face;Funding;Guidelines;Health;health care delivery;health data;health inequalities;Health Promotion;health science research;Health Sciences;Health system;Healthcare;High Prevalence;improved;Income;Individual;innovation;insight;Institution;International;Intervention;Interview;Justice;Knowledge;Laws;Life;Literature;Machine Learning;Methodology;Mission;Modeling;Morals;open data;Penetration;Phase;Policies;Population;population health;Procedures;Public Health;public health ethics;public health intervention;public health research;public trust;Recording of previous events;Records;Research;Research Ethics;Research Project Grants;Research Project Summaries;responsible research conduct;Sampling;Services;Social Sciences;solidarity;South Africa;Southern Africa;Structure;symposium;Technology;Three-Dimensional Imaging;tool;Transfer Agreement;Trust;Work


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

ORG_CITY: PROVO

ORG_DEPT: CHEMISTRY

ORG_NAME: BRIGHAM YOUNG UNIVERSITY

PHR: PROJECT NARRATIVE Single-cell proteome profiling promises to greatly benefit cancer research by providing insights into the tumor microenvironment, interactions between tumor cell types and specific responses to cancer therapies that cannot be determined using bulk measurements. While unbiased single-cell proteomics (SCP) has advanced rapidly in recent years, the sensitivity, throughput and quantitative performance of these measurements must dramatically improve to have a transformative impact on biomedical research. We will develop a novel platform for multiplexed SCP that quantifies >2000 proteins/cell at an unprecedented measurement throughput of >1000 cells/day.

PI_NAMEs: KELLY, RYAN T (contact)

PROGRAM_OFFICER_NAME: KYI, CINDY WIN

PROJECT_TERMS: Acceleration;Affect;anti-cancer research;Autophagocytosis;Biochemical;Biomedical Research;Breast Cancer Model;cancer cell;cancer therapy;Cell Physiology;Cell Separation;cell type;Cells;cost;Custom;Data;data acquisition;data standards;Development;Diagnostic;effective therapy;Exhibits;Experimental Designs;Fluorescence-Activated Cell Sorting;Heterogeneity;Immune response;immunoregulation;improved;Individual;individualized medicine;inhibition of autophagy;inhibitor;innovation;insight;instrument;instrumentation;Label;laser capture microdissection;Liquid Chromatography;liquid chromatography mass spectrometry;Malignant - descriptor;Malignant Neoplasms;mass spectrometer;Mass Spectrum Analysis;Measurement;Measures;Mediating;Molecular;nano;nanoDroplet;nanolitre;neoplastic cell;new technology;next generation;novel;novel strategies;Nucleic acid sequencing;Peptides;Performance;Phenotype;Pilot Projects;Population;Predisposition;Preparation;pressure;Process;protein expression;protein profiling;Proteins;Proteome;Proteomics;Reagent;Reporting;Reproducibility;Resistance;resistance mechanism;Resolution;response;RNA;Sampling;single cell sequencing;single-cell RNA sequencing;System;targeted treatment;Technology;Therapeutic;Time;Tissues;treatment group;triple-negative invasive breast carcinoma;tumor microenvironment

PROJECT_TITLE: Advanced Sample Preparation, Separation and Multiplexed Analysis for In-Depth Proteome Profiling of >1000 Single Cells Per Day


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Diabetes;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Nutrition;Racial and Ethnic Minority Health Research;Vascular Contributions to Cognitive Impairment and Dementia (VCID);Women's Health Research

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Persons with pre-diabetes and type 2 diabetes, females, and Hispanics are important risk groups for Alzheimer’s disease (AD) addressed in this proposal. Our proposal addresses several focus areas and milestones of the National Institute on Aging (NIA) AD + AD and related dementias (ADRD) Research Implementation Milestones including Population Studies, Precision Medicine and Health Disparities (milestones 1A,1C), Disease Mechanisms (2D, 2S), and Biomarkers and Diagnosis (9G).

PI_NAMEs: LUCHSINGER, JOSE ALEJANDRO (contact)

PROGRAM_OFFICER_NAME: ANDERSON, DALLAS

PROJECT_TERMS: Address;adjudication;Age;Age Years;aged;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer’s disease biomarker;Amyloid;Amyloid beta-Protein;Anatomy;apolipoprotein E-4;Applications Grants;Area;Atrophic;Biological Markers;Biological Specimen Banks;blood oxygen level dependent;Brain;Brain imaging;brain magnetic resonance imaging;Categories;Cephalic;cerebral atrophy;Cerebrovascular Disorders;Cognitive;cognitive performance;cohort;Communities;Cross-Sectional Studies;data repository;Dementia;Diabetes Mellitus;Diagnosis;Diffusion Magnetic Resonance Imaging;Discipline of obstetrics;Disease;Dyslipidemias;Education;Elements;executive function;Female;glucose tolerance;Goals;Gynecologic;health disparity;hispanic community;Hispanic Populations;Hormonal;Hypertension;Impaired cognition;improved;in vivo;Infarction;Inferior;Insulin;Life;longitudinal analysis;Magnetic Resonance Imaging;male;Medial;Mediating;Memory;Metabolic syndrome;middle age;mild cognitive impairment;National Institute on Aging;Nerve Degeneration;neuropathology;New York City;Non-Insulin-Dependent Diabetes Mellitus;Obesity;Outcome;Participant;Performance;Persons;Pharmaceutical Preparations;Plasma;Population Study;Positron-Emission Tomography;Precision Health;precision medicine;Prediabetes syndrome;primary outcome;Recording of previous events;recruit;Regional Disease;Research;Rest;Risk;Role;secondary outcome;sex;Sex Differences;Standardization;Structure;tau Proteins;Temporal Lobe;Testing;Thick;Time;uptake;vascular risk factor;verbal;Verbal Learning;White Matter Hyperintensity;Woman;women versus men

PROJECT_TITLE: Diabetes and brain amyloid in middle aged Hispanics

STUDY_SECTION: APDA

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


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Lyme Disease;Microbiome;Tickborne Diseases;Vector-Borne Diseases

ORG_CITY: KINGSTON

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF RHODE ISLAND

ORG_STATE: RI

PHR: The study of Bb transmission dynamics has been foundational for understanding the emergence of LD and other tick-borne diseases. This work will comprehensively expand this foundation by incorporating myriad effects of the tick microbiome to improve understanding of the Bb enzootic transmission cycle, which, in turn, directly informs LD risk. The conceptual and quantitative frameworks developed will be foundational for microbiome-informed vector-borne disease modeling in the future.

PI_NAMEs: COURET, JANNELLE  (contact);LORD, CYNTHIA C;NARASIMHAN, SUKANYA ;TSAO, JEAN

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: analog;Arthropods;Behavior;Behavioral;Black-legged Tick;Borrelia burgdorferi;Borrelia burgdorferi Group;Complex;cost;Costs and Benefits;Data;Development;differential expression;Disease;disease model;disorder risk;endosymbiont;Environment;enzootic;Etiology;experimental study;Fertility;Foundations;Future;Gene Expression;Gene Expression Profiling;Genes;Heritability;Horizontal Disease Transmission;Hydration status;improved;Incidence;Individual;Infection;Insecta;Investigation;laboratory experiment;Larva;Life Cycle Stages;life history;Lyme Disease;Measures;Mediating;metabolic rate;Metabolism;Microbe;microbial;microbiome;Modeling;mutualism;North America;Nutritional;Nymph;pathogen;Phenotype;Population;Prevalence;Public Health;Respiration;Rest;Rickettsia;RNA, Ribosomal, 16S;Role;Salivary Glands;Seasons;Sterility;success;symbiont;System;Testing;tick feeding;Tick-Borne Diseases;Ticks;Time;trait;transcriptome;transmission process;Variant;Vector-transmitted infectious disease;Vectorial capacity;Work

PROJECT_TITLE: Investigations of Lyme spirochete transmission as a complex network of microbial and ecological interactions


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Relevance Cytotoxic lymphocytes, which are critical for immune responses against viruses and cancer, kill infected or transformed target cells via specialized cell-cell contacts known as cytolytic immune synapses. This proposal seeks to understand how the dynamic physical activity of the cytolytic synapse and the mechanical properties of the lymphocyte and target cell contribute to the killing response. Understanding the biophysical basis of cytotoxic lymphocyte function could aid immunotherapeutic efforts to fight cancer and other diseases.

PI_NAMEs: HUSE, MORGAN A (contact)

PROGRAM_OFFICER_NAME: MALLIA, CONRAD M

PROJECT_TERMS: Actins;Address;Adhesions;Atomic Force Microscopy;Automobile Driving;base;Biochemical;Biological Models;Biomedical Engineering;biophysical techniques;Biophysics;cancer cell;cancer immunotherapy;Cell Communication;Cell Death Induction;cell killing;Cell membrane;Cell Physiology;Cell-Mediated Cytolysis;Cells;Cellular biology;Clinic;Clinical Data;Collaborations;Coupling;Cytoplasm;cytotoxic;Cytotoxic T-Lymphocytes;cytotoxicity;Data;Dimensions;Disease;Disseminated Malignant Neoplasm;Exertion;Extracellular Space;fighting;Genetic;Granzyme;Health;high resolution imaging;Human;Image;Immune;immune activation;immune function;Immune response;Immune Targeting;Immunity;Immunologic Surveillance;Immunological Models;immunological synapse;Immunotherapeutic agent;Immunotherapy;immunotherapy clinical trials;improved;In Vitro;in vivo;innovation;Integrins;intercellular communication;Intercellular Junctions;interdisciplinary approach;Invaded;Knowledge;Licensing;light microscopy;loss of function;Lymphocyte;Lymphocyte Activation;Lymphocyte Function;Lymphocyte Subset;Malignant Neoplasms;materials science;mechanical force;mechanical properties;mechanical signal;Mechanics;mechanotransduction;Mediating;Methods;Mission;Modeling;Molecular;mouse model;Mus;myocardin;Neoplasm Metastasis;novel;Output;pathogen;Peptide Hydrolases;perforin;Physical activity;Physiological;Positioning Attribute;Process;Property;Puncture procedure;Resolution;response;Role;Scientist;Shapes;Sorting;Specific qualifier value;Specificity;Stereotyping;superresolution imaging;Surface;Synapses;synaptic function;synergism;T-Lymphocyte and Natural Killer Cell;Time;transcription factor;transmission process;tumor;Tumor Immunity;United States National Institutes of Health;VDAC1 gene;Virus;Work

PROJECT_TITLE: Mechanoregulation of cytotoxic lymphocyte function


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Cannabinoid Research;Endocannabinoid System Research;Mental Health;Neurosciences;Substance Misuse;Therapeutic Cannabinoid Research

ORG_CITY: BOSTON

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: NORTHEASTERN UNIVERSITY

ORG_STATE: MA

PHR: PROJECT NARRATIVE The safe and effective treatment of alcohol abuse disorder (AUD), for which less effective FDA-approved medications currently exist, poses a major public health challenge in the United States. AM6527 is a CB1 neutral antagonist that has displayed its therapeutic value in relevant animal models, with a markedly reduced side-effect profile compared to previously known CB1 receptor inverse agonists. We now propose to advance AM6527 using the U01 mechanism toward IND-enabling studies for treating AUD.

PI_NAMEs: MAKRIYANNIS, ALEXANDROS  (contact)

PROGRAM_OFFICER_NAME: SENEVIRATNE, CHAMINDI

PROJECT_TERMS: 3-Dimensional;acamprosate;ADME Study;Adverse effects;Affect;Agonist;alcohol abuse therapy;Alcohol consumption;alcohol effect;alcohol intervention;alcohol reward;alcohol use disorder;Alcohols;analytical method;Anhedonia;Animal Model;antagonist;Behavioral;behavioral pharmacology;Biological Sciences;Canis familiaris;capsule;Cardiovascular system;Chemistry;Chromosome abnormality;Chronic;clinical development;Clinical Protocols;Clinical Research;clinical research site;CNR1 gene;Complement;Conduct Clinical Trials;Consent Forms;Cyclic GMP;Data;design;Development;Development Plans;Disease;Disulfiram;Dose;Drug Controls;drug of abuse;economic impact;Economics;effective therapy;Effectiveness;endogenous cannabinoid system;Epidemiology;FDA approved;Feeling suicidal;first-in-human;Formulation;genotoxicity;Goals;Heavy Drinking;High Pressure Liquid Chromatography;In Vitro;in vitro Assay;Intervention;Letters;manufacture;Measurement;Mediation;Mental Depression;Methods;micronucleus;Modeling;Mus;Naltrexone;Nausea;neurochemistry;nonhuman primate;novel;Oral;patient population;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacologic Substance;Pharmacology;Pharmacology and Toxicology;Population;pre-clinical;pre-Investigational New Drug meeting;preclinical safety;preclinical study;Preparation;product development;prototype;Public Health;Published Comment;Rattus;Reference Standards;relapse prevention;Reporting;Research;Residual state;respiratory;response;Rewards;rimonabant;Rodent;Safety;safety study;scale up;Self Administration;side effect;Societies;socioeconomics;Solvents;Specific qualifier value;Stress;Tablets;Therapeutic;Therapeutic Effect;Toxicokinetics;United States;Validation;verification and validation;Work

PROJECT_TITLE: CB1 Neutral Antagonists for Alcohol Use Disorder


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

ORG_CITY: LA JOLLA

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Blood-forming stem cells in the bone marrow regenerate blood and immune cells throughout life. Defects in stem cell maintenance lead to anemia, impaired immunity and leukemia, but the underlying cause of these defects in some human blood disorders are unknown. This proposal will examine if blood-forming stem cell maintenance and function are impaired by mutations in tRNAs, which are key molecules that support protein production.

PI_NAMEs: ACKERMAN, SUSAN L (contact);SIGNER, ROBERT A.J.

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Adult;Age;Amino Acids;analog;Anemia;Anticodon;Arginine;Arginine Specific tRNA;Biological Assay;Blood;Blood Cells;Bone Marrow;Bone marrow failure;Buffers;Cell Count;Cell Differentiation process;Cell Maintenance;Cell Physiology;cell type;Cells;ChIP-seq;chromatin immunoprecipitation;Codon Nucleotides;Data;Defect;Development;differential expression;Disease;Epitopes;Eukaryota;Failure;Family;fetal;fetal stem cell;fitness;Flow Cytometry;Gene Expression;Gene Mutation;Genes;Genetic;Genetic Transcription;Grant;Health;Hematological Disease;Hematopoiesis;Hematopoietic;Hematopoietic Neoplasms;hematopoietic stem cell self-renewal;Hematopoietic stem cells;Hematopoietic System;Hemorrhage;Heterogeneity;Housekeeping Gene;Human;Immune;Immunity;Immunologics;Impairment;Individual;Knock-in Mouse;Lead;leukemia;Life;Maintenance;Malignant - descriptor;Malignant Neoplasms;mammalian genome;member;Messenger RNA;mRNA Translation;Multigene Family;Mus;Mutation;Natural regeneration;Nature;Neonatal;Neurons;Non-Malignant;novel;Nuclear;Pancytopenia;Phenotype;polypeptide;Population;Production;progenitor;programs;Proliferating;Protein Biosynthesis;Proteins;Puromycin;reconstitution;Regulation;response;Ribosomal RNA;ribosome profiling;Ribosomes;RNA;RNA Polymerase III;Role;self-renewal;Signal Pathway;stem cell exhaustion;stem cell function;stem cell homeostasis;stem cell self renewal;stem cells;Stress;Testing;Tissues;transcriptome;transcriptome sequencing;Transfer RNA;Translations;Untranslated RNA;virtual;Work;young adult

PROJECT_TITLE: Transfer RNAs in Hematopoietic Stem Cell Function


NIH_SPENDING_CATS: Aging;Nutrition

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative Altered mitochondrial networking and energetics contributes to age-related diseases. Maintenance of mitochondrial networking is a function of the balance between rates of mitochondrial fission and fusion, which is, in turn, regulated by proteins localized at endoplasmic reticulum-mitochondria contacts or MAMs. Studies in this application will advance our understanding of the interplay between mTORC2 kinase and its downstream targets at MAMs in preventing age-related decline in mitochondrial fission and energetics.

PI_NAMEs: MARTINEZ-LOPEZ, NURIA ;SINGH, RAJAT  (contact)

PROGRAM_OFFICER_NAME: FU, YI-PING

PROJECT_TERMS: Age;age effect;age related;age related decline;age-related disease;aged;Area;Cell Culture System;Chronic;Clinical;Coupled;Data;dietary;Endoplasmic Reticulum;Equilibrium;Event;Exhibits;experimental study;extend lifespan;Failure;Fasting;Fatty Acids;Guanosine Triphosphate;hallmarks of aging;healthspan;Hydrolysis;Impairment;In Vitro;interest;Lead;life span;Liver;Maintenance;Membrane;mimetics;Mitochondria;mitochondrial dysfunction;mTOR inhibition;mTOR Inhibitor;Mus;mutant;NDRG1 gene;novel;Nutrient;Pathway interactions;phosphoproteomics;Phosphorylation;Phosphotransferases;prevent;Printing;Process;Protein Dephosphorylation;Proteins;Regulation;Respiration;Role;Signal Transduction;Sirolimus;Stress;System;Testing;Work

PROJECT_TITLE: Nutrient signaling at ER-Mitochondrial contacts and age-related mitochondrial dysfunction

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BN-Z(52)]


NIH_SPENDING_CATS: Autoimmune Disease;Diabetes;Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: NEW HAVEN

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative Epigenetic modifiers may affect the susceptibility of beta cells to immunologic damage. This proposal will test the role of one modifier, Tet2, which we have found can affect beta cell killing and may be modified to improve beta cell survival.

PI_NAMEs: HEROLD, KEVAN C (contact)

PROGRAM_OFFICER_NAME: AKOLKAR, BEENA

PROJECT_TERMS: Acceleration;Adoptive Transfer;Affect;Antigens;Appearance;assault;ATAC-seq;Attenuated;Autoantibodies;Autoimmune;Autoimmune Diabetes;autoimmune pancreatitis;autoimmune pathogenesis;Autoimmune Responses;Autoimmunity;Beta Cell;Biological Models;Bone Marrow Transplantation;Breeding;Cell Communication;cell killing;Cell Survival;Cells;chronic autoimmune disease;Clinical;clinical diagnosis;CRISPR/Cas technology;cytokine;Data;Development;Diabetes Mellitus;diabetogenic;Diagnosis;Dioxygenases;Disease;DNA Binding;DNMT3a;embryonic stem cell;Enzymes;Epigenetic Process;epigenome;epigenomics;Exposure to;Follow-Up Studies;Gene Expression;Genes;Glucose;Goals;Human;human embryonic stem cell;Hyperglycemia;Immune;immune activation;immunogenicity;Immunologics;Immunotherapy;improved;In Vitro;in vivo;Inbred NOD Mice;Individual;Inflammation;Inflammatory;inhibitor;Insulin;Insulin-Dependent Diabetes Mellitus;Investigation;islet;Islet Cell;Laboratories;Mediating;Methylation;Modification;mouse model;Mus;novel;novel strategies;Onset of illness;Pathogenicity;Pathway interactions;Patients;permissiveness;Play;Prediabetes syndrome;Predisposition;prevent;Production;programmed cell death ligand 1;Residual state;Resistance;response;Risk;RNA analysis;Role;Sampling;Signal Transduction;single cell analysis;Site;stem;T-Lymphocyte;Testing;Time;Tissues;transcription factor;transcriptome;transcriptomics;Transplantation;Work

PROJECT_TITLE: Adaptive epigenetic mechanisms of beta and immune cells in autoimmune diabetes

STUDY_SECTION: BMDM

STUDY_SECTION_NAME: Basic Mechanisms of Diabetes and Metabolism Study Section[BMDM]


ORG_CITY: PHILADELPHIA

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: Project Narrative This proposal focuses on developing a comprehensive understanding of the mechanism by which miR-21, an miRNA that is strongly associated with mouse and human SLE but yet poorly characterized, drives autoimmune responses and lupus nephritis. We will learn how an interplay of miR-21 and TLR7 signaling regulates B cell activation and metabolism in TLR7-promoted SLE. Finally, we will learn whether miR-21 or miR-21 regulated pathway(s) can be a therapeutic target for SLE.

PI_NAMEs: RAHMAN, ZIAUR  (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Affect;American;Antibodies;Asthma;Attenuated;Autoantibodies;Autoimmune;Autoimmune Responses;Autoimmunity;autoreactive B cell;B-Cell Activation;B-Lymphocytes;Binding Sites;Bone Marrow;Cells;Cellular Metabolic Process;comparison control;Cre lox recombination system;Data;Development;Disease;Disease Progression;Exhibits;Experimental Autoimmune Encephalomyelitis;extracellular;FRAP1 gene;Gene Expression;Genes;Grant;Helper-Inducer T-Lymphocyte;Human;human model;Immune;Immunity;inducible Cre;Inflammatory;Interferon Type I;Knowledge;Learning;Ligands;Lupus Nephritis;Malignant Neoplasms;Mediating;Metabolic;Metabolic Pathway;Metabolism;MicroRNAs;Modeling;mouse model;Mus;mutant;NF-kappa B;Oligonucleotides;Onset of illness;overexpression;Oxygen Consumption;Pathway interactions;Patients;Persons;Phenotype;PIK3CG gene;Plasma Cells;posttranscriptional;Production;Promoter Regions;Regulation;Regulator Genes;response;Role;Signal Pathway;Signal Transduction;Structure of germinal center of lymph node;systemic autoimmunity;Systemic Lupus Erythematosus;Tamoxifen;targeted treatment;Testing;therapeutic target;TLR7 gene;transcription factor;transcriptome sequencing

PROJECT_TITLE: miR-21 regulation of autoreactive B cell and lupus nephritis development

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


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Dental, Oral, and Craniofacial Disease;Genetics;Hematology;Human Genome;Infectious Diseases;Lymphatic Research;Lymphoma;Rare Diseases

ORG_NAME: TUFTS UNIVERSITY BOSTON

PHR: Narrative: As an orally transmitted pathogen, EBV translocates across the tonsillar epithelium and infects B cells, whereupon reaching the memory B-cell compartment, it silences nearly all of viral protein-coding genes to avoid immune detection. Here, we will investigate how lymphocyte metabolism pathways are subverted to cloak EBV’s presence, and how interventions such as restriction of the amino acid methionine can be used to reverse this silencing mechanism. The research promises to provide new directions in treatment of EBV-driven disease.

PI_NAMEs: GUO, RUI  (contact)

PROGRAM_OFFICER_NAME: MCNEALY, TAMARA L

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adult;Amino Acids;Antigens;Area;B-Lymphocytes;Biology;Burkitt Lymphoma;Carcinoma;career development;CD8-Positive T-Lymphocytes;Cell Compartmentation;Cells;Cellular Metabolic Process;chemical genetics;chronic infection;Clustered Regularly Interspaced Short Palindromic Repeats;Code;CRISPR screen;Data;derepression;Detection;Development;Development Plans;dietary restriction;Disease;DNA;DNA Methylation;DNA Modification Process;Double Stranded DNA Virus;Enzyme Inhibitor Drugs;Enzymes;Epigenetic Process;epigenetic regulation;epigenome;Episome;Epithelium;Epstein-Barr Virus latency;experimental study;Face;Folic Acid;folic acid metabolism;gene product;Genes;genetic approach;Genetic Transcription;Genome;genome-wide;Hairy Leukoplakia;histone methylation;histone modification;Human;Human Genome;Human Herpesvirus 4;Hypermethylation;Immune;immunogenic;Immunotherapy;infected B cell;Infection;Infectious Mononucleosis;insight;interdisciplinary approach;Intervention;Invaded;Jaw;Learning;Lymphocyte;Lymphoma;Lymphoma cell;Lymphoproliferative Disorders;Lytic Phase;Malignant Neoplasms;Membrane Proteins;Memory B-Lymphocyte;Mentors;Metabolic;Metabolic Control;Metabolic Pathway;Metabolism;metabolomics;Methionine;Methionine Metabolism Pathway;methyl group;Methylation;Nasopharynx Carcinoma;neoplastic cell;novel therapeutic intervention;Nuclear Antigens;Ocular orbit;Oncoproteins;Oral;Oropharyngeal;pathogen;Pathway interactions;Patients;Phase;post-transplant;Postdoctoral Fellow;programs;Proteins;Regimen;Research;Research Personnel;SA01;SA02;SA03;Saliva;small molecule;T cell response;T-Lymphocyte;Tongue;Tonsil;transmission process;tumor;Tumor Escape;Viral;Viral Antigens;Viral Genome;Viral Proteins;Virus

PROJECT_TITLE: Exploiting Metabolism to Uncloak Epstein-Barr Virus Immunogens in Latently Infected B-cells

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Infectious Diseases;Pediatric;Prevention

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Fluoridated drinking water has been praised as one of the 10 great public health achievements of the 20th century, but its growth has stalled, leaving over 100 million Americans with drinking water that is not fluoridated, and which probably never will be. Fluoridated bottled water represents a publicly-acceptable and potent strategy for dental caries prevention in underserved communities. To provide scientific evidence to justify the strategy, this study will undertake the first ever randomized controlled trial to evaluate dental caries preventive effects of fluoridated bottled drinking water in 3-year-old children.

PI_NAMEs: SLADE, GARY DOUGLAS (contact)

PROJECT_TERMS: 3 year old;4 year old;acceptability and feasibility;Achievement;Affect;Age;aged;American;Area;Biological Markers;biomarker validation;Caries prevention;Child;Clip;cohort;Communities;community advisory board;community intervention;Confidence Intervals;consumer demand;Consumer Preferences;Consumption;Data;Decayed, Missing, and Filled Teeth;deciduous tooth;Dental;Dental Anesthesia;Dental caries;Diffusion;Disease;distrust;drinking water;efficacy evaluation;Enrollment;experience;Family;Fluorides;follow-up;Future;General Anesthesia;group intervention;Growth;Health Benefit;Home;Household;improved;Income;indexing;Inequality;infancy;Infant;Ingestion;Intake;Intervention;intervention delivery;intervention effect;Intervention Studies;Label;Masks;Measures;Mediation;Medicaid eligibility;Method Acceptability;Methods;Modeling;Monitor;novel strategies;Nutritional;Observational Study;Oral health;Participant;Phase;phase 2 study;phase II trial;Placebo Control;Population;premature;Prevalence;prevent;Preventive;Primary Prevention;Probability;Public Health;Randomized;Randomized, Controlled Trials;Recommendation;recruit;Reporting;Research Design;Research Personnel;Safety;Sample Size;Sampling;sex as a biological variable;Site;Statistical Data Interpretation;Structure of nail of finger;Sum;System;systematic review;Testing;tooth surface;Treatment Efficacy;trial design;Uncertainty;underserved community;Water;Water consumption;Water fluoridation;Water Supply;Work;Writing

PROJECT_TITLE: Phase II, proof-of-concept randomized controlled trial to evaluate dental caries preventive effects of fluoridated bottle water


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Building Research Capacity at Institutions with Limited NIH Funding;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: SAN JOSE

ORG_NAME: SAN JOSE STATE UNIVERSITY

PHR: PROJECT NARRATIVE Diseases such as cancer and its development and progression, the pathogenesis of commensal microbes, and emergence of antimicrobial drug resistance are analogous to the process of adaptive evolution. Accordingly, the adaptation of biological systems poses a challenge to public health. A deeper understanding of how fungal pathogens respond and adapt to environmental stressors in biofilm states will lead to new treatment strategies and therapeutics.

PI_NAMEs: KAO, KATY C (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Adhesions;anti-fungal agents;anti-microbial drug;Biological Adaptation;biological systems;Candida;candida biofilm;Candida glabrata;Candidiasis;causal variant;Cells;Clinical;Color;combat;commensal microbes;Development;Disease;Drug resistance;emerging pathogen;Environment;environmental stressor;Essential Genes;Event;Evolution;Exhibits;experience;Fluconazole;Frequencies;Funding;Fungal Drug Resistance;Future;Gene Deletion;Genetic Determinism;genome sequencing;Genotype;Goals;Growth;Heterogeneity;High-Throughput Nucleotide Sequencing;Host Defense;Immunocompromised Host;In Vitro;in vivo;Individual;Kinetics;Knowledge;Laboratories;Lead;Libraries;Maize;Malignant Neoplasms;Maps;Mentorship;Methods;Microbe;Microbial Biofilms;Microbial Drug Resistance;minority trainee;Molecular;Monitor;Mutagenesis;mutant;Mutation;Mycoses;North America;novel therapeutic intervention;pathogen;Pathogenesis;pathogenic fungus;pathogenic microbe;Pharmaceutical Preparations;Phase;Phenotype;Population;Population Dynamics;Procedures;Process;Property;Public Health;Real-Time Systems;Research;Resistance;resistance gene;resistance mechanism;Sampling;Stress;stressor;Structure;Surface;System;Therapeutic;therapeutic development;therapeutically effective;Time;Training;Transposase;transposon sequencing;undergraduate student;Underrepresented Minority;underrepresented minority student;Universities;Visualization;Work

PROJECT_TITLE: Adaptive Evolution of Candida Biofilms


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: PROGRAM NARRATIVE  The CTSA Predoctoral T32 Program at The University of Texas Health Science Center at San Antonio will operate in collaboration with the Institute for Integration of Medicine and Science (IIMS), home for our CTSA. Predoctoral Trainees will be selected for an innovative 2-year program and trained to become the next- generation of translational scientists. The training in rigorous research, process innovation, systems thinking, and boundary crossing, along with team science and cultural diversity, will accelerate transformative breakthroughs and facilitate work in highly skilled, multidisciplinary teams that address threats to human health.

PI_NAMEs: CHUN, YONG-HEE PATRICIA (contact);FREI, CHRISTOPHER R.

PROGRAM_OFFICER_NAME: DIBELLO, ANTHONY THOMAS

PROJECT_TITLE: CTSA Predoctoral T32 at The University of Texas Health Science Center at San Antonio


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: Project Narrative: The proposed research improves public health because it will define factors that modulate DNA repair that directly control the outcome of genome editing therapies. Identifying factors that manipulate DNA repair pathways has the potential to advance these therapies for rare and common genetic diseases. This research addresses fundamental questions about mammalian DNA repair, which is relevant to the NIH’s mission of improving human health.

PI_NAMEs: HESS, GAELEN T (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Acceleration;Address;Cell Physiology;cell type;Cells;CRISPR/Cas technology;Dependence;DNA Repair;DNA Repair Pathway;Double Strand Break Repair;Equilibrium;Genetic Diseases;genome editing;Goals;Health;histone modification;Histones;Human;improved;Individual;innovation;Laboratories;Methods;Mission;Outcome;Pattern;Peptides;Process;Property;protein protein interaction;Proteome;Public Health;rare genetic disorder;recruit;Research;Role;screening;Site;Therapeutic;therapeutic development;therapeutic genome editing;Transcriptional Regulation;United States National Institutes of Health;Work

PROJECT_TITLE: Elucidating factors that modulate mammalian DNA repair to improve genome editing

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MGG-C(55)R]