NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Orphan Drug;Precision Medicine;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

PHR: Narrative Overexpression of FGFR1 is the driver abnormality in AML associated with the Stem Cell leukemia/lymphoma syndrome, an aggressive disease with very poor survival. Recent studies demonstrate a transcription factor function for FGFR1 and that genes it regulated allows escape from immune recognition. These studies will define genes responsible for these events with a view to developing novel therapeutic strategies for this disease.

PI_NAMEs: COWELL, JOHN K (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Affect;Apoptosis;B-Cell Lymphomas;bcr-abl Fusion Proteins;Binding;Bone Marrow Transplantation;cancer cell;Cell Compartmentation;Cell Maintenance;Cell Nucleus;Cell Proliferation;cell transformation;Cells;Chimeric Proteins;ChIP-seq;Chromosomal translocation;Chromosome abnormality;clinical remission;cofactor;Complex;Consensus;Cytogenetics;Cytoplasm;Cytotoxic agent;design;Development;Developmental Process;Disease;Disease remission;DNA Binding;Drug usage;Etiology;Event;experimental study;FGFR1 gene;Fibroblast Growth Factor Receptor 1;Frequencies;Gene Activation;Gene Expression;Genes;Genetic;genetic analysis;Genomics;Gleevec;Granzyme;Hematopoietic stem cells;Heterogeneity;Human;human disease;Imatinib;Immune;Immune Evasion;Immune system;Immune Tolerance;immunogenic;Immunosuppression;in vivo;in vivo Model;individualized medicine;insight;Length;leukemia;leukemia/lymphoma;Leukemic Cell;leukemic stem cell;Ligands;Maintenance;Malignant Neoplasms;Mass Spectrum Analysis;MicroRNAs;Modeling;Molecular;molecular subtypes;Molecular Target;mouse model;Mus;Myeloproliferative disease;Neoplasms;neoplastic cell;novel therapeutic intervention;Nuclear Proteins;Oncogenic;overexpression;partial response;Pathway interactions;Patients;personalized approach;Pharmaceutical Preparations;Phenotype;Phosphorylation;Phosphotransferases;Play;prevent;Process;Proliferating;protein activation;Protein Truncation;Proteins;Proteomics;Rare Diseases;rational design;Reporting;response;retroviral transduction;Role;Series;Signal Transduction;Stem Cell Development;stem cell expansion;stem cells;Survivors;Syndrome;System;T-Lymphocyte;targeted treatment;Thinking;Time;transcription factor;transcriptome sequencing;Transplantation;tumor;Tyrosine Kinase Domain;Up-Regulation

PROJECT_TITLE: Genetic Analysis of Myeloproliferative Disease

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ADMINISTERING_IC: EY

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Genetics;Human Genome;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: NEW YORK

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OPHTHALMOLOGY

ORG_FIPS: US

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: Keratoconus (KC) is a common vision-debilitating corneal dystrophy with an ill-defined polygenic basis and a complex etiopathology. We identified poor protective antioxidant responses and gene networks that regulate matrix and cellular functions in KC. Based on these premises, the current study will identify antioxidant biomarkers, disease-predisposing DNA variants by next generation sequencing, and establish patient-derived cell culture models to probe disease mechanisms and therapeutic agents.

PI_NAMEs: CHAKRAVARTI, SHUKTI  (contact)

PROGRAM_OFFICER_NAME: MCKIE, GEORGE ANN

PROJECT_TERMS: Abbreviations;Address;Adherent Culture;Adhesions;Adolescent;Affect;alternative treatment;Animal Model;Antioxidants;biobank;Biological;Biological Assay;Biological Markers;biomarker identification;Biomechanics;Blindness;Blood Cells;Candidate Disease Gene;Cell Culture Techniques;Cell Differentiation process;Cell Physiology;Cell Survival;Cells;Cellular Stress;CENPF gene;Cicatrix;Classification;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Collagen;comparison control;Complex;Cornea;Corneal dystrophy;corneal epithelium;CRISPR/Cas technology;crosslink;Cytoskeleton;Data;Databases;Defect;Development;Diagnosis;Disease;disease model;Disease susceptibility;disease-causing mutation;DNA;driving force;Early Diagnosis;Early treatment;Epithelial Cells;Etiology;exome;exome sequencing;Extracellular Matrix;Extracellular Matrix Proteins;Eye diseases;Family;Foundations;Functional impairment;Future;Gene Frequency;gene network;Genes;Genetic;genetic architecture;Genetic Predisposition to Disease;genome sequencing;genome wide association study;genome-wide;Goals;high risk;human induced pluripotent stem cells;improved;Individual;induced pluripotent stem cell;insight;Keratoconus;Keratoplasty;Lead;Liquid substance;Measurable;Measures;Mediating;migration;Minor;Modeling;Mutate;Mutation;next generation sequencing;Organoids;oxidative damage;Oxidative Stress;Pathogenesis;Pathogenicity;Patients;Penetrance;Peripheral Blood Mononuclear Cell;Persons;Physiological;Predisposition;Production;programs;Protein Secretion;Proteomics;Publishing;Regulation;response;Risk;Shapes;Sorting;Stratification;Stromal Cells;Testing;Therapeutic Agents;Thick;Thinness;Tissues;transcriptomics;translational impact;treatment strategy;Untranslated RNA;Variant;Vision;whole genome;Work

PROJECT_TITLE: Cellular and Genetic Defects in Keratoconus

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 2 Study Section[PED2]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Patient Safety

ORG_CITY: Aurora

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative As an NCI-designated comprehensive cancer center since 1997, the University of Colorado Cancer Center (UCCC) continues to provide significant leadership in the development and conduct of important translational and therapeutic clinical trials for cancer patients that improve the standard of care and extend the quality and quantity of life. As a stated goal of UCCC, mentorship and training of the next generation of investigators is part of our mission. In 2013, with the newly incorporated University of Colorado Health Systems (UCHealth), we integrated our flagship hospital (University of Colorado Hospital (UCH) with the Poudre Valley Hospital system and the Memorial Hospital system as the components of the LAPS institution (since 2014), and have been able to extend integrated clinical care and clinical research to a much larger segment of the Colorado and Wyoming population. This grant will benefit from the integrated electronic medical records, clinical management trial system, regulatory and fiscal management of clinical trials, and bring important clinical trials hours closer to cancer patients.

PI_NAMEs: ELIAS, ANTHONY D (contact)

PROGRAM_OFFICER_NAME: MOONEY, MARGARET M

PROJECT_TERMS: Adult;Award;Cancer Center;cancer clinical trial;Cancer Patient;Caring;Catchment Area;Clinical;clinical care;Clinical Management;Clinical Research;clinical research site;Clinical Trials;clinically relevant;Colorado;Communication;Comprehensive Cancer Center;Computerized Medical Record;Conduct Clinical Trials;Data;data management;Databases;Development;Disease;Ensure;Fostering;Goals;Grant;Gynecologic Oncology Group;Health system;Hospitals;Hour;improved;Infrastructure;Institution;Laboratory Scientists;Lead;Leadership;Life;Malignant Neoplasms;meetings;member;Mentorship;Mission;Modality;Molecular;Monitor;National Clinical Trials Network;National Surgical Adjuvant Breast and Bowel Project;next generation;Participant;patient safety;Patients;Pediatric Hospitals;Population;Positioning Attribute;Process;programs;Radiation Therapy Oncology Group;Reporting;Research;Research Personnel;Scientist;Side;Site;Southwest Oncology Group;standard of care;System;The University of Colorado Cancer Center;Therapeutic Clinical Trial;Therapeutic Trials;Training;translational clinical trial;Translational Research;Travel;Treatment Protocols;tumor;Universities;Wyoming

PROJECT_TITLE: NCI National Clinical Trials Network - Lead Academic Participant Sites


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Mental Health;Neurosciences

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE  Despite the significance of neurotransmitters norepinephrine (NE) and epinephrine (Epi) in a large number of physiological and pathological conditions, adrenergic transmission remains poorly understood, due primarily to limitations of available tools for monitoring NE/Epi. We propose to employ our newly developed high-performance GRABNE sensors (and sensor-based superresolution and deconvolution microscopic analysis algorithms) to define the unusual synaptic properties and functional role for adrenergic transmission, and thus build the baseline for the future translational and clinical NE research.

PI_NAMEs: BEENHAKKER, MARK  (contact)

PROGRAM_OFFICER_NAME: MATOS GALICIA, HEIDI YANICE

PROJECT_TERMS: Adrenergic Agents;Adrenergic Receptor;Algorithmic Analysis;Alzheimer's Disease;Arousal;Attention;Attentional deficit;autism spectrum disorder;Behavior;Biological Process;Brain;Cardiovascular Diseases;Cell Nucleus;Central Nervous System;Clinical;Cognition;cognitive function;Complex;Coupling;Data;Depressive disorder;Diffusion;Engineering;Epinephrine;Event;experimental study;Family;Future;G-Protein-Coupled Receptors;Gold;Green Fluorescent Proteins;Health;Heart;Human;Image Analysis;immunodeficiency;improved;Individual;Investigation;Link;locus ceruleus structure;Mental disorders;Microscopic;Monitor;monoamine;Mus;Nervous System Disorder;Neurons;neurotransmission;Neurotransmitters;Norepinephrine;novel;Organ;Output;Pancreas;Parkinson Disease;Pathologic;Performance;Peripheral;Peripheral Nervous System;Physiological;Physiological Processes;Play;Pontine structure;Preparation;Probability;Property;Receptor Activation;Regulation;Research;Resolution;Role;Scheme;Schizophrenia;sensor;Sensory;Signal Transduction;Site;Sleep;Sleep Disorders;Spleen;Synapses;Testing;Tissues;tool;transmission process;tumorigenesis;ultra high resolution;Visualization;Wood material

PROJECT_TITLE: Adrenergic transmission properties and implication

STUDY_SECTION: NC

STUDY_SECTION_NAME: Neuronal Communications Study Section[NC]


ADMINISTERING_IC: OD

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

ORG_CITY: WINSTON-SALEM

ORG_DEPT: PATHOLOGY

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: This application seeks continued support for a long-standing mentored research-training program for veterinarians. The program focuses on cardiovascular disease/diabetes, cancer biology, radiation effects, women’s health, microbiology and immunology, and regenerative medicine. Training typically leads to a PhD degree and provides the ability to conduct independent, investigator-initiated research.

PI_NAMEs: CLINE, J. MARK (contact)

PROGRAM_OFFICER_NAME: TANDON, RITESH

PROJECT_TITLE: Laboratory Animal & Comparative Medicine Training


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Hematology;Radiation Oncology;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: PROJECT NARRATIVE An effective National Cancer Clinical Trials (NCTN) must be led by centers with commitment to, and expertise in, the collaborative clinical trials process. The Medical College of Wisconsin (MCW) has a 45-year tradition of such commitment as demonstrated by scientific leadership in development and conduct of clinical trials in association with NRG Oncology, Alliance for Clinical Trials in Oncology, ECOG-ACRIN, and SWOG, in addition to leadership and substantial accrual to other National Cancer Institute (NCI)-funded trials networks.

PI_NAMEs: BRADLEY, WILLIAM H;GORE, ELIZABETH M;HAMADANI, MEHDI HUSSAIN;KURZROCK, RAZELLE ;WONG, STUART J (contact);YEN, TINA WF

PROJECT_TERMS: Address;Adult;American College of Radiology Imaging Network;Biometry;Blood;Bone Marrow Transplantation;cancer care;Cancer Center;cancer clinical trial;cancer diagnosis;cancer imaging;Cancer Patient;cancer prevention;cancer therapy;Clinical Research;Clinical Sciences;Clinical Trials;Clinical Trials Network;Conduct Clinical Trials;Dedications;Development;Discipline;Disease;Eastern Cooperative Oncology Group;empowerment;Ensure;experience;Faculty;Funding;Grant;Growth;Health;Hematology;Hematopoietic Stem Cell Transplantation;Human Resources;Individual;Information Technology;Informed Consent;Infrastructure;interdisciplinary approach;Intervention;Investments;Lead;Leadership;Logistics;Malignant Neoplasms;Master of Science;Medical Oncology;medical schools;member;Mentors;Methodology;Methods;Mission;Multi-Institutional Clinical Trial;Multicenter Trials;National Cancer Institute;National Clinical Trials Network;next generation;Oncology;operation;Outcome;Outcome Assessment;Phase;Physician Executives;Play;Positioning Attribute;pre-clinical;Process;programs;Publications;Radiation Oncology;Radiation therapy;Recording of previous events;recruit;Research;Research Personnel;Research Support;Resources;Role;Scientist;senior faculty;Site;skills training;Solid;Southwest Oncology Group;Standardization;Statistical Methods;Surgical Oncology;Technology;Training;Translational Research;treatment center;trial design;Wisconsin;Work;Writing

PROJECT_TITLE: MCW NCTN Lead Academic Participating Site


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: CORAL GABLES

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Project Narrative Despite the high risk for sleep-related morbidity, there is a paucity of data on sleep-disrupting psychosocial and environmental stressors associated with sleep deficiency (poor sleep, sleep apnea, and/or circadian misalignment) among older blacks. Our multi-disciplinary team will use novel mHealth devices recording sleep/activity cycles, light, noise, air quality, temperature, and greenspace exposure; novel brain biomarkers; and geospatial analytics to assess effects on sleep deficiency and delineate their role in explaining disparities in the brain and cognitive health of older blacks.

PI_NAMEs: JEAN-LOUIS, GIRARDIN  (contact)

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: Activity Cycles;Address;Adult;age related;Aging;Air;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease risk;Amyloid beta-Protein;Aphorisms;Area;Attention;Attitude;Award;Bayesian learning;Biological Markers;Biological Models;Black Populations;Blood Vessels;Brain;brain health;Brain Injuries;built environment;career;circadian;Circadian desynchrony;Circadian Dysregulation;Cognitive;cognitive function;Communities;Data;density;Devices;digital;Discrimination;Disparity;disparity reduction;dynamic system;Emotional;Enrollment;environmental change;Environmental Risk Factor;environmental stressor;ethnic minority;executive function;Exhibits;experience;Exposure to;Genetic;Glial Fibrillary Acidic Protein;Glucose;Glycosylated hemoglobin A;Goals;Green space;Health;health disparity;High Prevalence;high risk;Home;Household;Impaired cognition;indexing;Inflammation;innovation;interest;Interleukin-10;Interleukin-6;Intervention;Language;Leadership;Light;Link;Lipids;machine learning model;Memory;mHealth;Modeling;Moods;Morbidity - disease rate;multidisciplinary;Neighborhoods;Nerve Degeneration;Neurocognitive;Neurocognitive Deficit;neuropathology;Noise;novel;Obesity;Outcome;Pathogenesis;personalized intervention;Physiological;poor sleep;Population;pre-clinical;Prevention;psychosocial;Psychosocial Factor;psychosocial stressors;Public Health;racial minority;Research;Research Personnel;Risk;Role;Science;Shoulder;Sleep;Sleep Apnea Syndromes;Sleep Deprivation;Sleep Disorders;Sleep disturbances;social;social capital;Socioeconomic Status;Strategic Planning;success;tau Proteins;Temperature;Time;TNF gene;tool;Trail Making Test;Translational Research;translational study;United States National Institutes of Health;vascular contributions

PROJECT_TITLE: Mechanisms of sleep deficiency and effects on brain injury and neurocognitive functions among older blacks


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Cancer Genomics;Genetics;Human Genome

ORG_CITY: DURHAM

ORG_DEPT: SURGERY

ORG_NAME: DUKE UNIVERSITY

PHR: PROJECT NARRATIVE Millions of dollars are being expended to build single-cell maps of the cellular, genetic, and proteomic heterogeneity in human cancers. Easy-to-use and off-the-shelf models for visualizing extreme heterogeneity in genetically tractable systems will be necessary for translating the human cancer atlas into biological mechanisms of cancer progression and therapeutic resistance. This proposal is relevant to public health because it will provide first-of-kind technology, termed “MousePaint”, for visualizing massive tissue heterogeneity and experimentally mapping cancer evolution in genetically tractable animal models.

PI_NAMEs: SNYDER, JOSHUA CLAIR (contact)

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: 3-Dimensional;Animal Model;anti-cancer research;Atlas of Cancer Mortality in the United States;Atlases;Benchmarking;Big Data;Biological;Cancer Biology;cancer imaging;cancer invasiveness;Cancer Model;Cell Lineage;cell type;Cells;Color;combinatorial;Data Analyses;Developmental Biology;Elements;Engineering;Epithelium;Evolution;falls;Feasibility Studies;fitness;Fluorescence Microscopy;Future;Genetic;Genetic Research;Genetically Engineered Mouse;Genome;Genomic approach;Green Fluorescent Proteins;Growth;Heterogeneity;high reward;high risk;Histopathology;Human;human data;Image;Imaging Device;In Situ;In Vitro;in vivo;in vivo imaging;interest;Label;Laboratories;LacZ Genes;logarithm;Malignant - descriptor;Malignant Neoplasms;Maps;Measurement;Measures;Methods;Modeling;molecular pathology;mouse model;Mus;Natural History;Neoplasm Metastasis;neoplastic cell;Organ;Output;Paint;Pathologist;Performance;Phase;premalignant;programs;Proteins;Proteomics;Public Health;Reagent;Recurrence;Registries;Reproducibility;Research Personnel;Resistance;Resolution;single-cell RNA sequencing;stem cell biology;System;Techniques;Technology;Testing;Therapeutic;therapy resistant;Tissue Model;Tissues;tool;Training;transcriptomics;Transgenic Organisms;Translating;tumor;tumor heterogeneity;tumor progression;tumor-immune system interactions;tumorigenesis;Visualization;Visualization software

PROJECT_TITLE: Mouse Paint: A massively combinatorial approach for illuminating tumor heterogeneity in True Color


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Lung;Orphan Drug;Pulmonary Fibrosis;Rare Diseases

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

ORG_STATE: CA

PHR: NARRATIVE Our laboratory has been focused on elucidating the molecular mechanisms that regulate progressive pulmonary fibrosis for over two decades. The goals of this R35 application are to identify the epithelial- mesenchymal interactions that lead to unremitting fibrosis. Augmenting scientific knowledge in understanding the underlying mechanisms and the mode of actions of these interactions in lung fibrosis could significantly aid therapeutic development for patients with progressive pulmonary fibrosis.

PI_NAMEs: NOBLE, PAUL WESLEY (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Alveolar;Award;Awareness;Belief;beta-arrestin;Biology;CD44 Antigens;CD44 gene;Cells;Drug Targeting;Epithelium;Fibroblasts;Fibrosis;Freedom;Funding;Glues;Goals;Hyaluronan;idiopathic pulmonary fibrosis;Impairment;interest;Journals;Knowledge;Laboratories;Lung;man;Mesenchymal;Modeling;Molecular;Mus;next generation;Pathogenicity;Patients;Pharmaceutical Preparations;Phenotype;Publishing;Pulmonary Fibrosis;Pulmonary Inflammation;Regenerative capacity;Regulation;Research;Role;Science;Scientist;stem cell division;stem cell self renewal;therapeutic development;Therapeutic Intervention;Time;Training;Universities;Work

PROJECT_TITLE: Molecular Regulation of Progressive Pulmonary Fibrosis


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunization;Immunotherapy;Skin Cancer;Vaccine Related

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative In melanoma, PD-1 blockade has transformed the management of advanced and high-risk resectable disease with unprecedented improvements in progression-free and overall survival. However, non-response remains a pressing issue. Although still early in clinical development, agonists of Toll-like receptor 9 (TLR9) have demonstrated potential for the treatment of cancer. TLR9 agonists directly induce activation and maturation of plasmacytoid dendritic cells and enhance differentiation of B cells into antibody-secreting plasma cells. This project aims to investigate mechanisms of response and resistance to a novel clinical trial testing neoadjuvant immunotherapy with intra-tumoral CMP- 001 and nivolumab in high-risk resectable melanoma.

PI_NAMEs: DAVAR, DIWAKAR ;ZAROUR, HASSANE M (contact)

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: Adjuvant;Adjuvant Study;Adverse event;Affect;Agonist;anti-PD-1;anti-PD1 antibodies;Antibodies;Antigen Presentation;antigen-specific T cells;B cell differentiation;B-Lymphocytes;Binding;Biological;cancer infiltrating T cells;cancer therapy;Cancer Vaccines;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Death;Cell Maturation;Clinic;Clinical;clinical development;clinical efficacy;Clinical Trials;Combination immunotherapy;combinatorial;Consensus;CTLA4 blockade;Cytosine;Defect;Dendritic cell activation;Dendritic Cells;Disease;efficacy evaluation;Evaluation;exhaust;Exhibits;Experimental Models;Exposure to;first-in-human;Flow Cytometry;Guanosine;high risk;Human;immune checkpoint blockade;immunogenicity;Immunologics;Immunotherapy;immunotherapy trials;Impairment;improved;In complete remission;Interferon alpha;Interferon Type I;Interferons;Interleukin-10;Mediating;Melanoma;Melanoma Cell;Melanoma patient;Mus;Neoadjuvant Therapy;neoantigens;Neoplasm Metastasis;Nivolumab;novel;Pathologic;Patients;PD-1 blockade;Peptide Vaccines;phase III trial;Plasma Cells;primary endpoint;Production;programmed cell death protein 1;Property;randomized trial;recruit;Refractory;Relapse;relapse risk;Resectable;Resected;Resistance;response;RIPK3 gene;Signal Transduction;single-cell RNA sequencing;spectrograph;T cell infiltration;T cell receptor repertoire sequencing;T cell response;T-Lymphocyte;Testing;Therapeutic;Therapeutic Agents;TLR9 gene;Toxic effect;Translations;tumor;Tumor Antigens;Tumor Expansion;tumor microenvironment;Tumor Promotion;Vaccines

PROJECT_TITLE: Neoadjuvant Immunotherapy with Intratumoral CPG and PD-1 Blockade in Melanoma

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


ORG_CITY: PHILADELPHIA

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Healthy brain aging is key to extend the healthspan and glia play an important role but the molecular pathways involved are poorly understood. We have discovered that changes in social status in Harpegnathos ants induce an expansion in neuroprotective phagocytic glia, which is linked to a 5-fold extension of lifespan. Here, I will define the molecular pathways that regulate these remarkable events of glia plasticity and how they impact healthy brain aging and longevity.

PI_NAMEs: BONASIO, ROBERTO  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: Adult;Age;age related;age related neurodegeneration;aged;Aging;aging brain;aging related;Antibodies;Ants;Apoptosis;Behavior;Biological;Biological Assay;Biological Models;Brain;brain health;Brain Injuries;Brain region;Candidate Disease Gene;Castes;Cells;Data;defined contribution;Drosophila genus;epigenetic aging;Event;experimental study;extend lifespan;Family;Fluorescence Microscopy;Gene Expression Profile;Genes;Genetic;genetic manipulation;Genetic Transcription;Genome;Goals;healthspan;healthy aging;Homeostasis;Housekeeping;human old age (65+);Impaired cognition;In Vitro;in vivo;Insecta;knock-down;Life;life span;Ligands;Link;Longevity;Low-Density Lipoproteins;Mammals;Measures;Modeling;Molecular;Nerve Degeneration;Neuroglia;Neuronal Injury;Neurons;Neuropil;neuroprotection;Pathway interactions;Phagocytes;Phenotype;Physiology;Play;Population;Process;Proliferating;Property;receptor;Recombinants;Regulation;Reproduction;reproductive;response;response to brain injury;Role;Signal Transduction;single-cell RNA sequencing;social;Social Controls;Social status;Sorting;Testing;tool;Visualization;Vitellogenins;Work

PROJECT_TITLE: Social control of lifespan regulation via glial plasticity in ants


NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Macular Degeneration;Neurodegenerative

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Evidence suggests a role for pro-angiogenic macrophages in neovascular age-related macular degeneration pathogenesis, which is the leading cause of vision loss in the developed world. Our preliminary data demonstrates that macrophages are heterogeneous in experimental choroidal neovascularization (CNV) and that interleukin-7 receptor (IL7R) expressing macrophages are pro- angiogenic. In this proposal, we will determine the origin and function of IL7R+ macrophages during experimental CNV; these experiments will set the stage for potential cell-based therapies to simultaneously target multiple pro-angiogenic pathways via inhibiting IL7R+ macrophages.

PI_NAMEs: LAVINE, JEREMY A (contact)

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: Ablation;angiogenesis;Angiogenesis Pathway;Annexins;Area;Atrophic;Basement membrane;Blindness;Blood Vessels;Bone Marrow;Breeding;Cell Therapy;Cells;Choroid;choroidal angiogenesis;Choroidal Neovascularization;Classification;Complement;complement pathway;Complement Receptor;Confocal Microscopy;cytokine;Data;Dendritic Cells;diphtheria toxin receptor;Drusen;Endothelial Cells;experimental study;Exudative age-related macular degeneration;Eye;Fibronectins;Flow Cytometry;Fluorescence-Activated Cell Sorting;Genes;Heterogeneity;Homeostasis;Human;Immune;Inflammatory;Interleukin 7 Receptor;Interleukin-1 beta;intravitreal injection;Knock-out;Laser injury;Lasers;Lesion;LoxP-flanked allele;Lymphocyte;Macrophage;Maps;Matrix Metalloproteinases;Measures;Modeling;monocyte;Mus;novel;novel therapeutics;Ontology;Operative Surgical Procedures;osteopontin;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Patients;prevent;PTPRC gene;recruit;Resistance;Role;scaffold;single-cell RNA sequencing;System;T-Lymphocyte;Tamoxifen;targeted treatment;Testing;Therapeutic;transcriptome;Vascular Endothelial Growth Factors;Vision;Wild Type Mouse

PROJECT_TITLE: Investigating the function and mechanism of interleukin 7 receptor-expressing pro-angiogenic macrophages during experimental choroidal neovascularization


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Precision Medicine;Prostate Cancer;Urologic Diseases

PHR: Project Narrative Large chromosomal deletions are a hallmark of the cancer genome, but the role of such lesions in tumorigenesis has been significantly understudied due to the challenge of generating mouse models that accurately mimic such deletions. Our proposed work boldly aims to overcome this obstacle, and will contribute greatly to the implementation of precision oncology research, open new opportunities for modelling human diseases associated with large chromosomal deletions, and lead to novel insights into the biology of cancer-associated large deletions in prostate cancer, which will facilitate the identification of deletion-specific vulnerabilities that can be exploited for cancer treatment.

PI_NAMEs: CHEN, MING  (contact)

PROGRAM_OFFICER_NAME: BENAVIDEZ, JUSTIN MICHAEL

PROJECT_TERMS: Affect;Animal Model;arm;Biological;Cancer Biology;cancer genome;cancer initiation;cancer therapy;Characteristics;Chromosome Deletion;Chromosomes;Cloning;Code;conditional knockout;Credentialing;CRISPR/Cas technology;Data Set;Development;driving force;Embryo;Engineering;Epithelium;Event;Gene Targeting;Genes;Genetic;Genetically Engineered Mouse;Genome;genome editing;Genomic Segment;Goals;Grant;homologous recombination;Human;Human Chromosomes;human disease;human model;Impairment;in vivo;innovation;insight;Investigation;Knockout Mice;Lesion;LoxP-flanked allele;Malignant neoplasm of prostate;Malignant Neoplasms;Modeling;Mouse Embryonic Stem Cells;mouse model;Mus;Mutate;novel;Phenotype;precision oncology;pressure;Prevalence;probasin;Prostate;prostate cancer model;prostate carcinogenesis;Proteins;PTEN gene;Recurrence;Research;Research Personnel;Role;Sampling;Sequence Deletion;stem;Technology;Therapeutic;tool;Translational Research;Tumor Biology;tumor progression;Tumor Suppressor Genes;tumorigenesis;vector;Work

PROJECT_TITLE: Engineering Large Chromosomal Deletions in Mice to Advance Precision Oncology


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Hematology;Hodgkin's Disease;Human Genome;Lymphatic Research;Lymphoma;Orphan Drug;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE PIs: Ash Alizadeh, M.D./Ph.D. & Maximilian Diehn, M.D./Ph.D. In this study, we will use liquid biopsy to identify genetic subtypes in classical Hodgkin lymphoma. We will combine serial liquid biopsy measurements and imaging methods to refine prediction of how patients with classical Hodgkin lymphoma will respond to treatment. This work is relevant to public health because precision medicine has the potential to improve clinical outcomes of cancer patients and reduce sequelae.

PI_NAMEs: ALIZADEH, ASH ARASH (contact);DIEHN, MAXIMILIAN

PROGRAM_OFFICER_NAME: AGRAWAL, LOKESH

PROJECT_TERMS: Antibody-drug conjugates;Biological Assay;biological heterogeneity;Biological Markers;Biotechnology;Blood;cancer cell;cancer imaging;Cancer Patient;Cells;Clinical;clinical biomarkers;clinical heterogeneity;cohort;cytokine;Cytotoxic Chemotherapy;Dependence;Development;Diagnosis;Disease;Disease remission;disorder risk;DNA Sequence Alteration;Doctor of Medicine;Doctor of Philosophy;Event;exome;experimental study;Failure;Frequencies;gain of function;Genetic;genetic variant;Genomics;Genotype;Goals;Heterogeneity;high risk;Hodgkin Disease;Human;Human Herpesvirus 4;IL4 gene;Image;imaging modality;imaging study;immune checkpoint blockade;improved;indexing;Individual;induced pluripotent stem cell;innovation;insight;integration site;Interleukin 4 Receptor;liquid biopsy;Malignant Neoplasms;Measurable;Measurement;Measures;Metabolic;Methods;Modeling;Molecular;molecular marker;Monitor;Mutation;Nature;neoplastic cell;novel;novel therapeutic intervention;Outcome;outcome prediction;Pathologic;Pathway interactions;Patients;personalized medicine;personalized risk prediction;Phenotype;Plasma;Positron-Emission Tomography;pre-clinical;precision medicine;Precision therapeutics;Prediction of Response to Therapy;prognostication;Property;Public Health;Recurrence;Regimen;response;response biomarker;Risk;Risk Factors;risk prediction;risk prediction model;Signal Transduction;Somatic Mutation;STAT6 gene;Stereotyping;targeted treatment;Techniques;Testing;Therapeutic;therapeutic target;Therapeutically Targetable;therapy outcome;Toxic effect;Toxicity due to chemotherapy;Treatment Efficacy;Treatment Failure;Treatment outcome;tumor;tumor DNA;Tumor Tissue;Tumor Volume;Variant;Viral Genome;Work

PROJECT_TITLE: Circulating Genomic Determinants of Treatment Failure in Hodgkin Lymphoma

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


NIH_SPENDING_CATS: Breast Cancer;Cancer;Estrogen;Women's Health Research

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Narrative Estrogen receptor gene (ESR1) plays a major role in development, tissue homeostasis, and human cancer. The main goal of this proposal is to investigate the functional cross talk between ESR1 and the Hippo pathway, which is known to play a major role in organ size control and tumorigenesis. Completion of this project will not only address fundamental questions in ESR1 gene regulation and its role in Hippo biology, but also provide scientific basis for therapeutic intervention of the Hippo pathway for ESR1 expressing cancers, such as breast cancer.

PI_NAMEs: YANG, JING  (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: Address;Biology;Breast Cancer Cell;Breast Cancer therapy;Breast Cancer Treatment;cancer cell;cell growth;Development;drug resistance development;ESR1 gene;Estrogen decline;Estrogen receptor positive;Estrogen Receptors;Gene Expression Regulation;Goals;Growth;Homeostasis;hormone therapy;Human;immunogenicity;Immunotherapy;Laboratories;LATS1 gene;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Gland Parenchyma;Mediating;Medical;Molecular;novel;novel therapeutics;Nuclear;Organ Size;Pathway interactions;Phosphotransferases;Play;Receptor Gene;Regulation;Role;Signal Transduction;Therapeutic Intervention;therapy resistant;Tissues;transcription factor;Transcriptional Regulation;tumorigenesis

PROJECT_TITLE: Functional interplay between Hippo and estrogen receptor ESR1

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


NIH_SPENDING_CATS: Clinical Research;Lung;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Relevance Chronic respiratory disease is a leading cause of death in the U.S. and worldwide and the morbidity and mortality are closely linked to excess production of airway mucus. Despite the scope of this problem, there are no specific and effective therapies for prevention or reversal of this abnormality. The proposed studies aim to define and control the pathways leading to airway disease and thereby address a previously unmet need for treatment of a major public health problem.

PI_NAMEs: HOLTZMAN, MICHAEL J (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: 3-Dimensional;Address;Airway Disease;airway epithelium;airway repair;Asthma;Attenuated;Back;career development;Cause of Death;cell behavior;Cell Differentiation process;Cell Physiology;Cell Proliferation;Cell Reprogramming;Cell Separation;Cells;Cellular biology;cellular targeting;Charge;Chromatin;Chronic Obstructive Pulmonary Disease;chronic respiratory disease;Data;Disease;Drug Design;effective therapy;Environment;Epithelial Cells;epithelial stem cell;Extramural Activities;Functional disorder;Genomics;Goals;Homeostasis;Human;Immune;Immune response;Individual;Infection;innovation;Interruption;Link;Lung;lung development;Medical Research;Mentors;Mission;Mitotic;Molecular;Molecular Target;Morbidity - disease rate;mortality;mouse model;Mucous body substance;multidisciplinary;National Heart, Lung, and Blood Institute;novel strategies;Pathogenesis;Pathway interactions;Phosphotransferases;Population;porcine model;Prevention therapy;Production;programs;Proteomics;Public Health;Research;Research Personnel;Resources;respiratory virus;response to injury;Role;Scientist;stem cells;Structure;Technology;Therapeutic Intervention;Tissues;Training;translational impact;Transplantation;Universities;Validation;Viral;water channel;Work

PROJECT_TITLE: Defining and Controlling Airway Disease


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Patient Safety

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: PROJECT NARRATIVE In FY16, with clinical trials being an integral part of MDACC’s mission, we were able to treat more than 9,000 patients on approximately 1,000 interventional trials making significate contributions to the National Clinical Trial Network (NCTN). Not only were we able to enroll > 215 patients per year, but we were also able to provide robust trial enrollment, scientific and administrative leadership, and mentorship of early career faculty to participate in these important national trials. With the newly proposed NCTN LAPS UG1 grant, we will continue working towards our mission of eliminating cancer in Texas, nationally, and globally.

PI_NAMEs: HUNT, KELLY K;PINNIX, CHELSEA CAMILLE;TSAO, ANNE S (contact)

PROJECT_TERMS: Administrator;Adult;Advisory Committees;Area;Authorship;Blood;Blood specimen;Cancer Center;cancer therapy;Caring;Clinical Investigator;Clinical Research;Clinical Trials;Clinical Trials Cooperative Group;Clinical Trials Network;Communication;Data;data quality;Dedications;Development;Diagnostic Imaging;Discipline;early-career faculty;Education;Enrollment;Ensure;experience;Faculty;Funding;General Hospitals;Goals;Grant;Group Meetings;Gynecologic Oncology;imaging approach;Immunotherapy;Indigent;innovation;Institution;Intervention Studies;Intervention Trial;Lead;Leadership;Location;Malignant Neoplasms;Medical Oncology;member;Mentors;Mentorship;minority patient;Mission;multidisciplinary;National Clinical Trials Network;novel;operation;Operative Surgical Procedures;Pathology;Patient Care;Patients;Peer Review Grants;Pharmacology;Phase;Play;Prevention;Principal Investigator;programs;protocol development;Protocols documentation;Publications;Radiation Oncology;Rare Diseases;Reporting;Research;Research Design;research faculty;Research Personnel;Resolution;Role;Services;Site;skills;success;Surgical Oncology;Talents;Texas;Therapeutic;tissue biomarkers;Tissues;Translational Research;translational scientist;treatment trial;trial enrollment;Underinsured;Uninsured

PROJECT_TITLE: UT MD Anderson Cancer Center Network Lead Academic Participating Site (LAP) UG1


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Liver Cancer;Liver Disease;Nutrition;Rare Diseases

ORG_CITY: SAN ANTONIO

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: Project Narratives The pathogenesis of nonalcoholic steatohepatitis (NASH), a leading cause of cirrhosis and liver cancer, is poorly understood. Our recent study found that AMPK regulates caspase-6 activity to control NASH-associated liver injury. The proposed study will investigate the regulation and functions of a novel AMPK-caspase-6-BID axis in the development of NASH and dissect the underlying molecular mechanism.

PI_NAMEs: ZHAO, PENG  (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: 5'-AMP-activated protein kinase;Adopted;Affect;Alcoholic steatohepatitis;Amino Acids;Apoptosis;Apoptotic;Attenuated;BCL2 gene;BID protein;CASP3 gene;CASP6 gene;CASP8 gene;Caspase;Cell Death;Cell Line;Cells;Cessation of life;Choline Deficiency;Cirrhosis;Classification;conditional knockout;cytochrome c;Data;Development;Diet;Disease;drug development;effective therapy;Energy Metabolism;Enzyme Precursors;Equilibrium;Event;Family member;Fatty Liver;FDA approved;fibrogenesis;Fibrosis;Foundations;Functional disorder;Goals;Health;Hepatic Stellate Cell;Hepatocyte;HepG2;High Fat Diet;Homeostasis;Human;In Vitro;in vivo;Inflammation;islet amyloid polypeptide;knock-down;Knock-out;Knockout Mice;Lead;Liver;liver biopsy;Liver Fibrosis;liver injury;liver transplantation;Malignant neoplasm of liver;Mediating;Metabolic;Metabolic Control;metabolic phenotype;Metabolic stress;Molecular;mouse model;Mus;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;novel therapeutics;nutrition;Obesity;Overnutrition;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Phosphorylation;Physiology;Play;Prevalence;prevent;Primary carcinoma of the liver cells;Protein Family;Regulation;Repression;Research;Risk;Role;Science;sensor;Signal Transduction;stellate cell;Therapeutic;therapeutic development;therapeutic target;Transgenic Mice;Virulence Factors

PROJECT_TITLE: A novel pathway controls liver injury in NASH

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

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

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE Loss of all or part of chromosome 7 is among the most common chromosomal abnormalities in high-risk myeloid diseases, yet the precise genetic and mechanistic contributions of these deletions remain unknown. There are many purported myeloid regulators and tumor suppressor genes on 7q, suggesting 7q may be a contiguous gene syndrome region in which the loss of multiple neighboring genes contributes to disease. This proposal aims to leverage CRISPR/Cas9 gene editing to model 7q deletions in vivo and identify combinatorial gene deficiencies that drive myeloid disease, and define the mechanisms by which dosage imbalances contribute to disease development.

PI_NAMEs: JOTTE, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: GILLASPY, ALLISON

PROJECT_TERMS: Abnormal Karyotype;Acceleration;Acute leukemia;Adult;Anemia;animal model development;Apoptosis;Automobile Driving;Bioinformatics;Blood;career;CD34 gene;cell growth;Cell Proliferation;Cells;Chromatin;Chromosome 7;chromosome 7q loss;Chromosome abnormality;Cleavage Under Targets and Release Using Nuclease;Clonal Expansion;combinatorial;CRISPR/Cas technology;Cytogenetics;cytopenia;Data;data integration;derepression;Development;Diploidy;Disease;dosage;Dose;Doxycycline;druggable target;Dysmyelopoietic Syndromes;Dysplasia;Electroporation;Engineering;Environment;Epigenetic Process;Erythropoiesis;Etiology;experimental study;EZH2 gene;Gene Combinations;Gene Deletion;Gene Dosage;Genes;Genetic;Genetic Transcription;Genomics;Hematopoiesis;Hematopoietic stem cells;high risk;Histones;Homeobox;Human;In Vitro;in vivo;Ineffective Hematopoiesis;K-562;K562 Cells;Karyotype;knock-down;Knock-out;knockout gene;Knowledge;Lead;Leukemic Cell;Maintenance;Malignant Neoplasms;Methodology;Methyltransferase;Modeling;Molecular;Molecular Abnormality;Monosomy 7;mouse model;Mus;Mutation;Myelogenous;Myeloid Cells;Myelopoiesis;Myeloproliferative disease;Neoplasms;new therapeutic target;novel therapeutics;Onset of illness;Outcome;Pathogenesis;Pathogenicity;pediatric myelodysplastic syndrome;Peripheral;Physicians;Population;Prognosis;Recurrence;Research Personnel;Risk;Role;Scientist;Series;skills;small hairpin RNA;stemness;Syndrome;Synteny;Technical Expertise;Techniques;Training;Transcription Alteration;transcription factor;transcriptome sequencing;Transplantation;Treatment Efficacy;Tumor Suppressor Genes;Work

PROJECT_TITLE: Defining the Pathogenesis of Del(7q) in Hematopoietic Stem Cells


NIH_SPENDING_CATS: Clinical Research;Congenital Structural Anomalies;Kidney Disease;Pediatric;Polycystic Kidney Disease

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Vasopressin is a hormone that regulates water balance, blood pressure and contributes to progression of non-diabetic, diabetic, and polycystic kidney disease (PKD), through mechanisms that are still unclear. Vasopressin production was thought to be limited to the brain, but we have evidence that it is also made in the kidney. This project aims to understand the role that kidney-derived vasopressin plays in health and disease using cells and transgenic mouse models with a targeted deletion of vasopressin in the kidney.

PI_NAMEs: ARROYO ORNELAS, JUAN PABLO (contact)

PROGRAM_OFFICER_NAME: RANKIN, TRACY L

PROJECT_TERMS: absorption;Academic Medical Centers;Adult;Affect;Amino Acids;Antibodies;aquaporin-2;Award;Binding;Blood Pressure;Body Weight decreased;Brain;career development;Cell Polarity;Cell Proliferation;Cells;Chronic Kidney Failure;Cyst;Cyst Fluid;Data;Development;Development Plans;Diabetic Nephropathy;Disease;Distal;Duct (organ) structure;Ductal Epithelial Cell;Educational workshop;Epithelial Cell Proliferation;Equilibrium;Extracellular Fluid;Financial Support;Fluids and Secretions;Functional disorder;G-Protein-Coupled Receptors;Growth;Health;Hormones;Human;Hypotension;Hypothalamic structure;In Vitro;Institution;Kidney;Kidney Diseases;kidney epithelial cell;Knockout Mice;Measures;Mediating;Medical Faculty;Medicine;Mentorship;Modeling;mortality;mouse model;Mus;Nephrology;Nephrons;new therapeutic target;non-diabetic;novel;Patients;Phosphorylation;Physiological;Physiology;Plasma;Play;Polycystic Kidney Diseases;Population;prevent;pro-vasopressin;Production;Proliferating;Rattus;Receptor Activation;Receptor Signaling;Regulation;Renal function;Reproducibility;Research Personnel;Role;Signal Transduction;Stimulation of Cell Proliferation;Stimulus;Stress;Teacher Professional Development;Testing;Transgenic Mice;V2 Receptors;Vasopressins;Water;water channel;Work

PROJECT_TITLE: Understanding the physiology and pathophysiology of kidney-derived vasopressin


NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Genetics;Human Genome;Neurodegenerative;Neurosciences;Opioids

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: NARRATIVE In glaucoma, retinal ganglion cells (RGCs) slowly and progressively degenerate leading to visual impairment. We have shown hypoacetylation, decline in neurotrophic factors, and an increase in DNA methylation in ocular hypertensive animals. These changes were reversed by δ-opioid-receptor activation and subsequently provides RGCs neuroprotection.

PI_NAMEs: HUSAIN, SHAHID  (contact)

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: Acetylation;Acute;Affect;Agonist;Animals;Apoptotic;Appearance;Astrocytes;ATAC-seq;Attenuated;Binding;Biomechanics;Blindness;Brain-Derived Neurotrophic Factor;Cataract;Cell Death;Cell Physiology;Characteristics;Chromatin Structure;Chronic;Clinical Treatment;Complex;CpG Islands;CREB1 gene;cytokine;Data;Decitabine;delta opioid receptor;Dependence;deprivation;DNA Methylation;DNA Modification Methylases;DNMT3a;DNMT3B gene;Epigenetic Process;Etiology;Event;Exhibits;Eye;Gene Expression;Genes;genome-wide;Glaucoma;Glial Fibrillary Acidic Protein;Goals;Histone Acetylation;Histone Deacetylase;Histones;Homeostasis;Hypermethylation;Immunohistochemistry;Inflammatory;inhibitor;Injury;innovation;Laboratories;Lead;Measures;Mediating;Methylation;Modeling;Modification;mRNA Expression;Mus;Nerve Degeneration;Neurodegenerative Disorders;neuroprotection;neurotrophic factor;novel;novel strategies;novel therapeutics;Ocular Hypertension;Opioid;Optic Disk;Optic Nerve;optic nerve disorder;Outcome;Pain management;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;Physiologic Intraocular Pressure;Physiological;prevent;Primary Open Angle Glaucoma;Promoter Regions;protein expression;Rattus;Rattus norvegicus;Receptor Activation;Regulation;response;Retina;Retinal Ganglion Cells;Retinoblastoma;Risk Factors;Role;STAT3 gene;Stress;Testing;Therapeutic;transcription factor;Transcription Initiation Site;transcriptome sequencing;Visual impairment;Work

PROJECT_TITLE: Opioid-Induced Epigenetic Mechanisms in Glaucoma


NIH_SPENDING_CATS: Diabetes;Maternal Health;Nutrition;Obesity;Pediatric;Pregnancy;Prevention;Women's Health Research

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Pregnancy conditions such as prediabetes, obesity, and gestational diabetes mellitus can exacerbate maternal insulin levels causing changes in placental function, altering nutrient availability to fetal metabolic tissues and predisposing the offspring to metabolic disease in childhood and adulthood. Yet, very little information is known about the role of insulin signaling in placental function and the mechanistic link between maternal hyperinsulinemia and the programming of metabolic disease in the offspring. We expect that the results from the proposed work will ultimately lead to new understanding of the effects of high maternal insulin during pregnancy on placental nutrient delivery to the fetus that may cause programming of metabolic disease, and this new knowledge could improve clinical management of patients, and thus improve women's reproductive health and pregnancy outcomes.

PI_NAMEs: ALEJANDRO, EMILYN  (contact)

PROGRAM_OFFICER_NAME: SILVA, CORINNE M

PROJECT_TERMS: Address;Adult;Amino Acid Transporter;Amino Acids;Beta Cell;Binding;Cell membrane;Cell Physiology;Childhood;Circulation;Clinical;Clinical Management;Data;detection of nutrient;Development;Environmental Risk Factor;experience;fetal;Fetal Development;Fetal Growth;Fetus;FRAP1 gene;Genetic;Genetic Models;Gestational Diabetes;Glucose;Glucose Intolerance;glucose tolerance;Glucose Transporter;GLUT 4 protein;Grant;Growth Factor;Health;Hormones;Hyperinsulinism;improved;in utero;in vivo;innovation;Insulin;Insulin Receptor;Insulin Resistance;insulin secretion;insulin signaling;Insulin-Like-Growth Factor I Receptor;Knowledge;Leucine;Life;Link;Longitudinal cohort;Mediating;Metabolic;Metabolic Diseases;Modeling;Molecular;Mothers;mTOR protein;Non-Insulin-Dependent Diabetes Mellitus;Nutrient;Nutrient availability;Obesity;offspring;Outcome;parous;Patients;Phosphotransferases;Physiological;Placenta;pre-clinical;Pre-Clinical Model;Prediabetes syndrome;Pregnancy;Pregnancy Outcome;Pregnant Women;prevent;Process;Radiolabeled;receptor;Receptor Signaling;Risk;Role;Signal Transduction;SLC2A1 gene;Structure of beta Cell of islet;success;Testing;Tissues;trafficking;Weight Gain;women's reproductive health;Work

PROJECT_TITLE: Placental Insulin Signaling and mTOR Nutrient-Sensing Programming of Offspring Metabolic Health

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA MEDICAL RESEARCH FOUNDATION

ORG_STATE: OK

PHR: NARRATIVE This project aims to establish a powerful tracking system for studying cells generated in the thymus. This system is necessary for supporting the new hypothesis that thymus can produce innate lymphoid cells. It will also help the isolation of these cells and determining their functions, as well as other studies of T cell biology.

PI_NAMEs: SUN, XIAO-HONG  (contact)

PROGRAM_OFFICER_NAME: PRABHUDAS, MERCY R

PROJECT_TERMS: Biological;Biological Assay;Blood;Bone Marrow;Bone Marrow Cells;Bone Marrow Transplantation;Brain;CD3 Antigens;Cell Lineage;Cell Ontogeny;Cell Physiology;Cell Separation;cell type;Cells;Cellular biology;Common Lymphoid Progenitor;Complex;Data;Dependence;detection platform;Enterobacteria phage P1 Cre recombinase;Exhibits;experimental study;field study;Future;Generations;Genes;Growth;Heterozygote;IL7R gene;Internal Ribosome Entry Site;Knock-in Mouse;Label;Laboratories;Lung;Lymphoid;Lymphoid Cell;lymphoid organ;Monitor;Mouse Strains;Mus;novel;Nude Mice;Organ;Pattern;Peripheral;polypeptide;Population;Production;Proteins;PTPRC gene;Reagent;Reporter;Reporter Genes;Research;response;Series;single-cell RNA sequencing;Small Intestines;Source;Specificity;stem cells;Surface;System;T-Cell Development;T-Lymphocyte;Testing;Thymus Gland;Tissues;tool;Transcript;transcriptome;Transgenes;Translating;Transplantation;Validation

PROJECT_TITLE: Establishing a lineage tracing system for studying thymus-derived innate lymphoid cells

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: SAN FRANCISCO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Recent theoretical models and empirical studies have highlighted glutamate as a key neurotransmitter in the pathophysiology of depression that may be an important target for novel fast-acting antidepressants. However, given the dynamic nature of the metabolism of glutamate (which can be metabolized as part of the Krebs cycle in neurons or converted to glutamine in astrocytes via mitochondrial enzymes), it is critical to develop novel imaging methods that will clarify which aspects of glutamatergic metabolism is altered by depression. Thus, the goal of the present study is to establish the reliable detection of dynamic glutamate metabolism in depressed individuals using proton and deuterium magnetic resonance spectroscopy at ultrahigh magnetic fields (7 Tesla) combined with oral intake of deuterated glucose and to develop novel metabolic metrics that will provide insight into this debilitating condition.

PI_NAMEs: HO, TIFFANY CHEING;LI, YAN  (contact)

PROGRAM_OFFICER_NAME: WIJTENBURG, SARAH ANDREA

PROJECT_TERMS: Adult;Affect;Age;Agreement;Anterior;anti-depressive agents;Astrocytes;Benchmarking;Blood Glucose;Brain;brain based;Carbon;cingulate cortex;Citric Acid Cycle;clinical application;Data;Depressed mood;depressed patient;Detection;Deuterium;Disease;Dose;Enzymes;Exhibits;Functional disorder;Future;gamma-Aminobutyric Acid;Glucose;Glutamate Metabolism Pathway;Glutamates;Glutamine;Goals;Image;imaging modality;Individual;innovation;insight;Intake;Isotopes;Ketamine;Kinetics;Label;magnetic field;Magnetic Resonance Spectroscopy;Magnetism;Major Depressive Disorder;Measures;Mental Depression;Metabolic;metabolic imaging;metabolic rate;Metabolism;Methodology;Methods;Mitochondria;mitochondrial dysfunction;Modeling;Nature;Neurons;neurotransmission;Neurotransmitters;Noise;novel;Oral;Oral Administration;Patients;Persons;Protocols documentation;Protons;recruit;Reproducibility;Research;Resolution;Sampling;Scanning;sex;Signal Transduction;Spectrum Analysis;Techniques;temporal measurement;Testing;Theoretical model;Time;tool;Tricarboxylic Acids

PROJECT_TITLE: Integrating 1H MRS with 2H-Labeled Glucose to Characterize Dynamic Glutamate Metabolism in Major Depressive Disorder

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CN-M(90)S]


NIH_SPENDING_CATS: Cancer;Genetics

PHR: PROJECT NARRATIVE Alkylation damage is one of the most commonly encountered types of DNA damage induced by environmental agents as well as by cancer chemotherapeutics. Our group recently discovered a new signaling pathway by which human cells sense such damage. We now have evidence that the cell senses alkylation damage initially on RNA, which in turn is used to activate a signal to promote DNA repair. This proposal seeks to understand this novel paradigm in maintaining genomic integrity and its role in cancer treatment.

PI_NAMEs: MOSAMMAPARAST, NIMA  (contact)

PROGRAM_OFFICER_NAME: OKANO, PAUL

PROJECT_TERMS: Alkylating Agents;Alkylating Antineoplastic Agents;Alkylation;Biochemical;BRCA1 gene;cancer therapy;Cell Nucleus;Cell Survival;Cells;Chemoresistance;Chemosensitization;chemotherapy;Chemotherapy-Oncologic Procedure;Coal;Common Neoplasm;Complex;Data;Dealkylation;DNA;DNA Alkylation;DNA Damage;DNA Repair;environmental agent;Event;Evolution;Excision;Exposure to;Funding;gene repression;genetic approach;Genetic Transcription;Genome;genome integrity;Glioblastoma;Grant;helicase;Human;Hybrids;improved;in vitro activity;inhibitor;innovation;kinase inhibitor;Lesion;Maintenance;Malignant Neoplasms;Mediating;Mediator;Methyltransferase;Modality;Modeling;Nature;novel;Nuclear;Nucleic Acids;Organism;overexpression;p53-binding protein 1;Pathway interactions;patient derived xenograft model;Phosphorylation;Phosphotransferases;Play;prevent;reconstitution;recruit;Repair Complex;repaired;Resistance;response;RNA;RNA methylation;Role;Serinus;Signal Pathway;Signal Transduction;small molecule;small molecule inhibitor;Testing;Therapeutic;tool;treatment response;tumor;Ubiquitin;ubiquitin-protein ligase;upstream kinase;virtual;Work

PROJECT_TITLE: Damaged RNA as a mediator of alkylation responses

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


NIH_SPENDING_CATS: Clinical Research;Immunotherapy;Kidney Disease;Organ Transplantation;Regenerative Medicine;Transplantation

ORG_DEPT: PEDIATRICS

PHR: PROJECT NARRATIVE Kidney disease is a growing health problem worldwide, but the development of new treatments to stop or reverse kidney damage has remained limited. The present application uses patient-derived, adult kidney organoids to enable a new way to study kidney disease in the laboratory, in particular how different cells in the kidney interact with one another. This approach will enhance our understanding of kidney diseases and enable the creation of new targeted therapies to treat them.

PI_NAMEs: SUTHA, KEN  (contact)

PROJECT_TERMS: 3-Dimensional;Acute;Acute Renal Failure with Renal Papillary Necrosis;Adult;Affect;Air;allograft rejection;Allografting;Architecture;Basic Science;Bioinformatics;Biopsy;Biopsy Specimen;career;CD3 Antigens;Cell Death;Cell Survival;Cells;Childhood;Chronic Kidney Failure;Cisplatin;collaborative environment;Complex;Culture Techniques;cytokine;Data;Development;Disease;Doctor of Philosophy;drug development;Environment;Epithelial Cells;Epithelial-Stromal Communication;Epithelium;Equilibrium;experience;Experimental Models;Feasibility Studies;Fibroblasts;Fibrosis;Functional disorder;Future;gene panel;Goals;Graft Rejection;Growth;Health;Heterogeneity;Human;Immune;immune activation;immune cell infiltrate;immunological diversity;Immunosuppression;Immunotherapy;improved;In Vitro;in vitro Model;indexing;induced pluripotent stem cell;Infiltration;Injury;injury and repair;Injury to Kidney;innovation;insight;Intervention;Kidney;kidney allograft;kidney cell;Kidney Diseases;Kidney Transplantation;Knowledge;Laboratories;Ligands;Liquid substance;loss of function;Mediating;Mentors;Mentorship;Modeling;Morphology;multiplexed imaging;Muromonab-CD3;nano-string;Natural regeneration;nephrogenesis;Nephrology;nephrotoxicity;new therapeutic target;novel;novel strategies;novel therapeutics;Organ Transplantation;organoid transplantation;Organoids;Pathogenesis;Patients;pediatric department;Persons;Phenotype;Physicians;Platelet-Derived Growth Factor;Population;preservation;Process;Prospective Studies;receptor;reconstitution;renal damage;repaired;Research;Resolution;Resources;response;Sampling;Scientist;Signal Transduction;single cell analysis;single-cell RNA sequencing;skills;Structure;T-Lymphocyte;targeted treatment;Techniques;Testing;Therapeutic;therapeutic development;Tissues;Training;transcriptomics;Transforming Growth Factor beta;Translating;Translational Research;transplant model;Transplantation;Transplantation Immunology;transplantation therapy;treatment response;Tubular formation;tumor;tumor-immune system interactions;Universities;Work

PROJECT_TITLE: Patient-Derived Kidney Organoids For Modeling Kidney Injury

STUDY_SECTION: DDK

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


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Caregiving Research;Clinical Research;Dissemination and Implementation Research;Patient Safety;Pediatric;Prevention

ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE Children with medical complexity (CMC) have a high risk of experiencing medication related harm but can benefit from interventions that involve their caregivers as co-designers. This award will support the candidate’s (1) training in participatory, human centered design and (2) skill development in implementation and evaluation research to design and test interventions fit for unique needs of CMC.

PI_NAMEs: ABEBE, EPHREM  (contact)

PROGRAM_OFFICER_NAME: PATEL, ANURADHA DIPAK

PROJECT_TERMS: Academy;Address;Admission activity;Adopted;Adult;American;Award;Behavior Therapy;Behavioral Model;care coordination;career development;Caregivers;Caring;Child;Child health care;Complex;Consolidated Framework for Implementation Research;Continuity of Patient Care;cost;Data;design;Discharge Plannings;Effectiveness;effectiveness/implementation hybrid;Engineering;Ensure;Evaluation Research;evidence base;experience;Failure;Family;Family Caregiver;Future;future implementation;Goals;Health Personnel;Healthcare;Healthcare Systems;high risk;Home;Hospitals;Human;human centered design;implementation research;improved;Individual;Inpatients;Intervention;Interview;Joints;Knowledge;Laws;Literature;Maps;Measures;Medicaid;Medical;Medication Management;medication safety;Modeling;Output;Participant;patient oriented;patient population;patient safety;Patient Self-Report;Patients;pediatric patients;Pediatrics;Performance;Persons;Pharmaceutical Preparations;Phase;prevent;Professional Role;prototype;Randomized, Controlled Trials;Recommendation;Regimen;Reporting;Research;Research Personnel;Resources;Risk;Role;Safety;Schedule;skill acquisition;Solid;Specific qualifier value;Statutes and Laws;success;successful intervention;System;Technology;Testing;text searching;therapy design;therapy development;tool;Training;United States National Institutes of Health;usability;Visual;Work

PROJECT_TITLE: A Systems Approach to Improve Safe Medication Management for Children with Medical Complexity


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Infant Mortality;Patient Safety;Pediatric;Precision Medicine;Rare Diseases;Transplantation

ORG_CITY: CLEVELAND

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: Project Narrative  The proposed research is relevant to public health because patients with tetralogy of Fallot, the most common cyanotic congenital heart disease affecting ~1:2500 babies, have increased risk of heart failure and premature death despite excellent initial surgery. Development of non-invasive, easily obtained, and rapidly implemented metrics of ventricular mechanics are needed to improve prediction of death and allow optimization of pulmonary valve replacement timing. This project is relevant to the NHLBI’s mission because the tools developed here, and the skills learned, could then be applied to other forms of congenital and structural heart disease, and promote longer and more fulfilling lives for patients.

PI_NAMEs: TANDON, ANIMESH  (contact)

PROGRAM_OFFICER_NAME: COADY, SEAN

PROJECT_TERMS: Address;Adult;Adverse event;adverse outcome;Affect;Age;Apical;Arrhythmia;Biomedical Engineering;Cardiac;cardiac magnetic resonance imaging;Cardiology;Cardiovascular system;career;Cessation of life;Characteristics;Clinical;clinical practice;Clinical Research;cohort;Computer Models;computer science;congenital heart abnormality;Cyanotic heart disease;Data;Data Analytics;Data Set;Death Rate;Dedications;design;Development;early experience;EFRAC;Environment;Excess Mortality;experience;Failure;Funding;Geometry;Goals;Guidelines;Heart Diseases;Heart failure;human old age (65+);Image;image processing;improved;improved outcome;Interdisciplinary Study;Intervention;kinematics;Lead;Learning;Learning Skill;Left;Left Ventricular Ejection Fraction;Left Ventricular Function;Machine Learning;Magnetic Resonance Imaging;Measures;Mechanics;Mentors;Mission;Modeling;Morbidity - disease rate;Motion;multidisciplinary;National Heart, Lung, and Blood Institute;novel;Obstruction;Operative Surgical Procedures;Outcome;outcome prediction;Patient-Focused Outcomes;Patients;Pediatric cardiology;Performance;Population;Positioning Attribute;predict clinical outcome;predicting response;Predictive Value;premature;prospective;Prospective cohort;Prospective Studies;Public Health;Pulmonary Valve Insufficiency;pulmonary valve replacement;Randomized, Controlled Trials;Recording of previous events;repaired;Research;Research Design;Research Personnel;responders and non-responders;response;Right Ventricular Hypertrophy;Risk;Shapes;standard of care;structural heart disease;Techniques;Testing;Tetralogy of Fallot;Time;tool;Training;vector;Ventricular;Ventricular Fibrillation;Ventricular Tachycardia;Work

PROJECT_TITLE: Novel Cardiac MRI-Based Predictors for Tetralogy of Fallot: Deformation, Kinematic, and Geometric Analyses

STUDY_SECTION: MPOR

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


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Aging;Bioengineering;Cardiovascular;Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Heart Disease - Coronary Heart Disease;Maternal Health;Pediatric;Pregnancy;Social Determinants of Health;Women's Health Research

ORG_CITY: NEW DELHI

ORG_COUNTRY: INDIA

ORG_FIPS: IN

ORG_NAME: CENTRE FOR CHRONIC DISEASE CONTROL

PHR: Project Narrative The current proposal titled, “1/2-GEOHealth Health Effects of Selected Environmental Exposomes Across the Life CourSe (HEALS)-India”, aims to study effect of environmental exposomes: PM2.5, NO2, O3, and extremes of temperature, on multiple health outcomes using a modified life course approach to inform policy interventions.

PI_NAMEs: PRABHAKARAN, DORAIRAJ  (contact);REDDY, SRINATH K;SCHWARTZ, JOEL D;SIEBER, NANCY CAROL L.

PROGRAM_OFFICER_NAME: JESSUP, CHRISTINE

PROJECT_TERMS: Acceleration;Address;Adolescence;Adolescent;Adult;adverse birth outcomes;Advisory Committees;Affect;age related;Aging;Air Pollutants;Air Pollution;Anthropometry;Area;arterial stiffness;Birth;Blood Pressure;Carbon;Cardiovascular Diseases;Cardiovascular system;Child;Childhood;Chronic;Chronic Disease;cognitive development;cohort;Complex;Country;Cross-Sectional Studies;Data;Development;Diameter;Disease;DNA Methylation;early childhood;Education;Elements;Environmental Exposure;Environmental Health;Epigenetic Process;epigenome;experience;extreme temperature;frailty;Future;Gender;Genomic Segment;Gestational Diabetes;Glucose;Grant;Growth;Health;human old age (65+);Human Resources;Hypertension;Impaired cognition;improved;Incidence;Income;indexing;India;Individual;Inequality;infancy;Infrastructure;infrastructure development;Insulin;Intervention;Joints;land use;Level of Evidence;Life;Life Cycle Stages;life span;Link;Location;Long-Term Effects;low and middle-income countries;Low Birth Weight Infant;machine learning prediction;Measurement;Measures;Mediating;Mentors;Metabolism;Metals;Meteorology;methylation pattern;Modeling;Modification;Monitor;mortality;muscle strength;Myocardial Infarction;Nerve Degeneration;Nitrogen Dioxide;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;older adult;Outcome;Ozone;Participant;Particulate Matter;Pattern;Physical Performance;Policies;Pollution;Population;Populations at Risk;Pre-Eclampsia;predictive modeling;Predisposition;Pregnancy;Pregnancy Complications;Premature Birth;programs;Public Health;Research;Research Support;Research Training;Resolution;Retrospective Studies;Risk;Role;Rural;Sampling;Scanning;Science;Scientist;sex;Socioeconomic Status;socioeconomics;spatiotemporal;Temperature;Testing;therapy design;Time;Training;urban setting;Vulnerable Populations;Work

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-Q(70)R]


ED_INST_TYPE: SCHOOLS OF PHARMACY

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

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: Project Narrative In modern sanitary conditions, humans (and laboratory rodents) no longer encounter entire classes of environmental and commensal microorganisms that can shape effective and appropriate immunoregulatory circuits. This reduction in microbial input may drive development of hyperactive pathological neuroinflammatory responses and associated behavioral deficits (cognitive impairments, depression, etc.). Here we will reveal in rats whether a microbial-based treatment strategy, that is approved for use in humans (Mycobacterium vaccae immunotherapy; NCTC 11659), prevents age-associated neuroinflammation and postoperative cognitive decline.

PI_NAMEs: FONKEN, LAURA K (contact)

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: Address;Adult;Age;age related;age related neuroinflammation;aged;Aging;aging brain;aging population;aging related;Alzheimer's Disease;animal old age;Anti-Inflammatory Agents;Bacteria;Behavioral;Brain;Cells;Central Nervous System;Clinical;Cognitive deficits;commensal microbes;Communication;Dementia;Development;Elderly;Environment;Exposure to;Genus Mycobacterium;Goals;Human;Hygiene;Hyperactivity;Hypersensitivity;Immune;immune function;Immune response;Immune system;immunoregulation;Immunotherapy;Impaired cognition;improved;Infection;Inflammation;Inflammation Mediators;Inflammatory;inflammatory milieu;Inflammatory Response;innovation;Interleukin-1 beta;Interleukin-10;Interleukin-4;Laboratories;Malignant Neoplasms;Mediating;Meningeal;Mental Depression;Microbe;microbial;microbial based therapy;Microglia;microorganism;Modeling;Modernization;Molecular;Morbidity - disease rate;mortality;neural;Neuroimmune;neuroinflammation;novel;older patient;Operative Surgical Procedures;Pathologic;patient subsets;Patients;Peripheral;Pharmaceutical Preparations;pharmacologic;Population;post-operative cognitive dysfunction;Postoperative Period;pre-clinical;prevent;Process;protective effect;Quality of life;Rattus;Research;response;Risk;Risk Factors;Rodent;Role;Shapes;Signal Pathway;Signal Transduction;Societies;Soil;Sterility;Stimulus;Stress;Subcutaneous Injections;T-Lymphocyte;Therapeutic;Therapeutic Uses;Toxic effect;transcriptomics;transmission process;treatment strategy;virtual;Work

PROJECT_TITLE: Targeting age-related neuroinflammation and postoperative cognitive decline: a microbial-based approach

STUDY_SECTION: NNRS

STUDY_SECTION_NAME: Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section[NNRS]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Gene Therapy;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Prevention

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE With recent advances in disease modeling and therapeutic genome editing, there is now the opportunity to tackle two distinct but interrelated challenges in cardiovascular care. First, how to interpret clinical sequencing data to better determine who is at risk for cardiovascular diseases. Second, how to prevent vulnerable patients from developing these diseases. My laboratory is seeking to address both of these challenges in the coming years.

PI_NAMEs: MUSUNURU, KIRAN  (contact)

PROGRAM_OFFICER_NAME: HASAN, AHMED A  K

PROJECT_TERMS: Address;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;Caring;Cause of Death;clinical sequencing;Coronary heart disease;Data;Diabetes Mellitus;Diagnosis;Disease;disease model;DNA;empowerment;functional genomics;gene function;Genes;genome editing;human genomics;insight;Laboratories;lipid metabolism;novel;novel strategies;Patients;Play;prevent;Prevention;Research;Role;Technology;therapeutic genome editing;Therapeutic Uses;Untranslated RNA;Variant;variant of unknown significance

PROJECT_TITLE: Diagnosis, Prevention, And Treatment Of Cardiovascular Diseases With Genome Editing


NIH_SPENDING_CATS: Biotechnology;Digestive Diseases;Foodborne Illness;Immunization;Immunotherapy;Infectious Diseases;Vaccine Related

PHR: PROJECT NARRATIVE Astroviruses are a global cause of gastroenteritis, commonly known as stomach flu, but currently there are no vaccines or treatments available to protect against these viruses. Cytotoxic T cells are immune cells important for killing infected cells and preventing future infections, and while these cells are critical to combat astroviruses, little is known about how they specifically engage astrovirus-infected cells. Understanding the specific aspects of the virus that T cells target and characterizing how protective T cell responses develop are both critical to advance astrovirus vaccines and therapies.

PI_NAMEs: BALDRIDGE, MEGAN T (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Acute;adaptive immunity;Adoptive Transfer;Age;Alleles;Animal Model;Anti-viral Agents;anti-viral efficacy;Antibody Response;Astrovirus;B-Lymphocytes;Blood;Bone Marrow Transplantation;Cattle;CD3 Antigens;CD8-Positive T-Lymphocytes;Cell Physiology;Cell Therapy;Cells;Cellular Tropism;Childhood;Chronic;chronic infection;Clinical;combat;Cytotoxic T-Lymphocytes;Data;Development;Diarrhea;Elements;Encephalitis;Enteral;Epithelial Cells;Epitopes;Family suidae;flu;Foundations;Future;Gastroenteritis;Genetic Recombination;Genomics;Goals;Grant;High Prevalence;Human;Immune;Immune response;Immunity;Immunocompetent;Immunocompromised Host;immunodeficiency;Immunodeficient Mouse;Immunodominant Epitopes;Immunologics;immunoregulation;Impairment;in vivo;Individual;Infant;Infection;Innate Immune Response;insight;Interferons;intestinal epithelium;Intestines;Investigation;Memory;Meningitis;mesenteric lymph node;Methods;MHC Class I Genes;Modeling;mouse model;Mucosal Immune Responses;Mus;Norovirus;older patient;Organ;pathogen;Pathogenesis;pathogenic virus;peptide I;Peptide Library;Peripheral Blood Mononuclear Cell;Phenotype;Phylogenetic Analysis;prevent;Protocols documentation;Reagent;Reporting;Research;Resolution;Risk;RNA Viruses;Role;Sampling;screening;Seroprevalences;Small Intestines;Spleen;Splenocyte;Stomach;T cell response;T cell therapy;T-Lymphocyte;T-Lymphocyte Epitopes;Therapeutic;Tissues;tool;Tropism;Turkey bird;Vaccination;Vaccine Design;Vaccine Therapy;Vaccines;Viral;Virus;virus development;Virus Diseases;virus tropism;Wild Type Mouse;Work;Zoonoses

PROJECT_TITLE: Defining astrovirus-specific T cell responses

STUDY_SECTION: CMIA

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Radiation Oncology

PHR: PROJECT NARRATIVE Understanding how tumors respond to radiotherapy is critical to producing new molecularly targeted treatments that overcome radiation resistance and improve survival for cancer patients. Based on our preliminary data, we predict that p21 activated kinases cause resistance to radiotherapy and that by targeting these kinases we can sensitize tumors to radiotherapy. In this proposal, we will investigate the mechanisms though which p21 activated kinases produce resistance to radiotherapy which will allow us to develop biomarker driven treatment approaches to increase radiotherapy's ability to destroy tumors while decreasing side effects.

PI_NAMEs: ADVANI, SUNIL J (contact)

PROGRAM_OFFICER_NAME: PRASANNA, PAT G

PROJECT_TERMS: Address;Affect;Antibody-drug conjugates;Attention;biomarker driven;Biosensor;cancer cell;Cancer Histology;Cancer Patient;cancer survival;cancer therapy;Categories;cell killing;Cells;chemotherapy;Chemotherapy and/or radiation;Clinical;clinical translation;clinically relevant;curative treatments;cytotoxic;Cytotoxic Chemotherapy;Data;delivery vehicle;Diagnosis;DNA Damage;DNA Repair;Drug Delivery Systems;Drug Sensitization;Drug usage;extracellular;Family;flexibility;Foundations;Frustration;genetic approach;Goals;Heterogeneity;homologous recombination;Human;improved;improved outcome;inhibitor;innovation;insight;Ionizing radiation;kinase inhibitor;Label;Link;Malignant Neoplasms;Mediating;MEKs;Methods;Modeling;Molecular;Molecular Target;molecular targeted therapies;Morbidity - disease rate;Mus;neoplastic cell;Nonmetastatic;Normal tissue morphology;novel;novel therapeutics;Oncogenes;Organ;p21 activated kinase;p21-activated kinase 1;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Penetration;peptide drug;Peptide Hydrolases;Peptides;Pharmaceutical Preparations;pharmacologic;Phosphorylation;Phosphotransferases;Play;Process;Prodrugs;radiation resistance;Radiation therapy;Radiation Tolerance;Radiation-Sensitizing Agents;radioresistant;Radiosensitization;Resistance;response;Role;Schedule;Serine;side effect;Signal Pathway;Signal Transduction;small molecule;subcutaneous;Techniques;Technology;Testing;Therapeutic;Therapeutic Index;tool;Toxic effect;Translating;Treatment Efficacy;tumor;Tumor Cell Line;tumor microenvironment;Tumor Tissue;tumor xenograft;tumorigenesis;tumorigenic;Unresectable;Work

PROJECT_TITLE: Elucidation and therapeutic exploitation of PAK mediated radioresistance

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Dissemination and Implementation Research;Drug Abuse (NIDA only);HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Opioid Misuse and Addiction;Opioids;Patient Safety;Prevention;Substance Misuse

ORG_CITY: PROVIDENCE

ORG_NAME: RHODE ISLAND HOSPITAL

ORG_STATE: RI

PHR: PROJECT NARRATIVE  Long-acting injectable medications for both HIV and Opioid Use Disorder have the potential to dramatically improve adherence by eliminating the need for daily pill-taking. While treating these two conditions concurrently with long-acting injectables holds promise, currently little is known about whether offering this integrated treatment approach is feasible, acceptable, or effective for this population. This study seeks to address this limitation by developing and pilot testing a clinical protocol to guide the delivery of combined long-acting injectable treatment for HIV and Opioid Use Disorder.

PI_NAMEs: LANGDON, KIRSTEN JOHNSON (contact);RICH, JOSIAH D

PROGRAM_OFFICER_NAME: WEBB, CANDACE KARONDELETTE

PROJECT_TERMS: addiction;Address;Adherence;Adverse event;AIDS prevention;antiretroviral therapy;Attitude;Behavior;behavior change;Buprenorphine;Caring;Clinic;Clinical;Clinical Protocols;community reentry;Criminal Justice;Death Rate;Development;Diagnosis;Disease Progression;disorder risk;Drug usage;Drug user;Effectiveness;effectiveness/implementation study;evidence base;Face;future implementation;Goals;Guidelines;Health;high risk;HIV;HIV Infections;HIV risk;Hybrids;implementation barriers;improved;Incidence;Individual;Injectable;injection drug use;integrated care;interest;Intervention;Interview;Jail;Knowledge;life span;Measures;medication compliance;medication for opioid use disorder;Medicine;Modeling;multiple chronic conditions;novel;opioid agonist therapy;opioid use;opioid use disorder;Oral;Outcome;Outpatients;Participant;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacy facility;Phase;pill;pilot test;point of care;Population;Prevention;Prisons;prospective;Provider;Quality of life;Research;Research Design;resistant strain;Risk;Risk Taking;Safety;safety and feasibility;Sampling;satisfaction;secondary outcome;service utilization;Services;substance use;Substance Use Disorder;System;Target Populations;Testing;therapy adherence;therapy development;transmission process;treatment services;uptake;Viral;Viral Load result;viral resistance

PROJECT_TITLE: Integrating Long-Acting Injectable Treatment to Improve Medication Adherence among Persons Living with HIV and Opioid Use Disorder

STUDY_SECTION: HIBI

STUDY_SECTION_NAME: HIV/AIDS Intra- and Inter-personal Determinants and Behavioral Interventions Study Section[HIBI]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE This study examines the function of MYCT1, a gene that is dysregulated in cultured human HSCs, in the control of endocytosis, a crucial regulatory step that multiple signaling pathways need to execute cell fate decisions. Our work will illuminate the mechanisms by which MYCT1 controls stemness and cell fate in HSCs by integrating extracellular signaling cues, which will provide new insight to the culture- associated HSC dysfunction. These studies may provide new strategies to restore compromised transplantability of ex vivo expanded human HSCs, and ultimately help expand clinical applications of human HSCs.

PI_NAMEs: MIKKOLA, HANNA KATRI ANNIKKI (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Address;Affect;Biological Assay;Blood;Blood Cells;Cell Cycle Progression;Cell division;Cell Line;Cell Physiology;Cells;Clinical;clinical application;Cues;Data;Endocytosis;Endosomes;Endothelial Cells;Engraftment;Environment;Equilibrium;ethnic bias;ethnic minority;expression vector;extracellular;Functional disorder;functional improvement;gain of function;Gene Expression;Genes;Hematologic Neoplasms;Hematological Disease;Hematopoiesis;Hematopoietic Cell Production;hematopoietic stem cell expansion;hematopoietic stem cell niche;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Human;improved;Inherited;insight;Kinetics;knock-down;Life;Link;loss of function;Mediating;MLLT3 gene;Modeling;Molecular;Mus;mutant;Natural regeneration;novel;novel strategies;overexpression;Patients;prevent;process improvement;programs;Proteins;Receptor Signaling;Regulation;response;self-renewal;Signal Pathway;Signal Transduction;stem cell division;stem cell function;stemness;TGFBR1 gene;TGFBR2 gene;Therapeutic;Transforming Growth Factor beta;Transplantation;transplantation therapy;Vesicle;Work

PROJECT_TITLE: MYCT1 as a moderator for signaling between human HSC and their niche

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


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases

ORG_CITY: TUCSON

ORG_NAME: LUCEOME BIOTECHNOLOGIES, LLC

ORG_STATE: AZ

PHR: Project Narrative Toxoplasma gondii is the causative agent of toxoplasmosis, a debilitating disease in immunocompromised individuals, and current treatments have been shown to have severe side effects. Development of assays against new targets will help advance the discovery of new and effective therapies for this deadly disease. The purpose of our application is to develop low-cost assays for the Toxoplasma gondii kinome and chemical probes to inform upon the biology of the parasite.

PI_NAMEs: ZUTSHI, REENA  (contact)

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: Acceleration;acute infection;Anti-malarials;asexual;assay development;Binding;Biological Assay;Biology;Bioluminescence;Biotechnology;Cells;chemical conjugate;Chemicals;chronic infection;Communities;contaminated water;cost;Cost of Illness;Data;design;Development;Dimerization;Disease;drug development;drug discovery;Drug Targeting;effective therapy;Encephalitis;Eye diseases;Genome;Goals;Growth;high throughput screening;Human;human disease;Hybrids;Immunocompetent;Immunocompromised Host;In Vitro;in vivo;Individual;Infection;Ingestion;inhibitor;innovation;Intervention;Invaded;kinase inhibitor;Letters;Libraries;Life Cycle Stages;Light;Luciferases;luminescence;Malaria;Meat;Motility;novel therapeutics;Parasites;Pathology;pharmacophore;Phase;Phosphotransferases;Plasmodium falciparum;Population;Pregnant Women;prevent;Production;Publications;Pyrimethamine;Reporting;Research;research and development;Scaffolding Protein;screening;side effect;Signal Pathway;success;Sulfadiazine;System;Technology;Toxoplasma;Toxoplasma gondii;Toxoplasmosis;transmission process;Treatment Protocols;uncooked;United States;Vertical Disease Transmission;Virulence;women patients

PROJECT_TITLE: Enabling Toxoplasma gondii Kinome Directed Drug Discovery


NIH_SPENDING_CATS: Diabetes;Obesity

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Plasminogen activator inhibitor type 1 (PAI-1/ SerpinE1) and type 2 (PAI-2/ SerpinB2) are serine protease inhibitors of tissue plasminogen activator and urokinase. In contrast to well-known pathologic role of PAI-1 in metabolic syndrome, our preliminary data indicate that PAI-2/ SerpinB2 plays a protective role in obesity- induced insulin resistance. Understanding the mechanisms involved in maintaining glucose tolerance by PAI-2/ SerpinB2 will significantly improve our knowledge on drug development to treat insulin resistance.

PI_NAMEs: DUTTA, PARTHA  (contact)

PROGRAM_OFFICER_NAME: BASU, RAJATAVA

PROJECT_TERMS: Adipose tissue;Age;Alteplase;Anti-Inflammatory Agents;Apoptosis;Apoptotic;Binding;Body mass index;Caspase;Cells;cytokine;Data;Diabetes Mellitus;diabetic patient;Disease;drug development;Exhibits;experimental study;extracellular signal-regulated kinase 4;Frequencies;Genetic Transcription;GKLF protein;Glucose Clamp;glucose tolerance;Hematopoietic;Human;Hyperinsulinism;impaired glucose tolerance;improved;In Vitro;in vivo;Individual;Inflammation;Inflammatory;inhibitor;Insulin Resistance;insulin sensitivity;Interferon Gamma Receptor Complex;Interferon Type II;Interleukin-1 beta;Interleukin-13;Interleukin-4;Knowledge;Macrophage;Malignant Neoplasms;MAPK3 gene;Measures;Mediating;Metabolic syndrome;Mitogen-Activated Protein Kinases;Molecular;monocyte;Mus;nanoparticle;Nematode infections;non-diabetic;Obese Mice;Obesity;overexpression;Pathogenesis;Pathologic;Patients;Plasminogen Activator Inhibitor 1;Plasminogen Activator Inhibitor 2;Play;Prevention;Process;Production;promoter;Proteins;receptor;Role;Serine Proteinase Inhibitors;Small Interfering RNA;Source;T-Lymphocyte;Testing;Thinness;Tissues;TNF gene;transcription factor;transcriptome;transglutaminase 2;Urokinase;Visceral;Wild Type Mouse

PROJECT_TITLE: The role of SerpinB2 in insulin resistance and inflammation

STUDY_SECTION: BMDM

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


ORG_CITY: LITTLE ROCK

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: PROJECT NARRATIVE Inverse hemodynamic response (IHR), an inappropriate reduction of cerebral blood flow in response to increased neuronal activity, is a shared pathological event in seizure, traumatic brain injury, and other neurological disorders, and is an emerging significant contributor to the pathophysiology of these neurological diseases. Using combined pharmacological and genetic approaches, this project will test a novel hypothesis that the seizure-induced IHR is mediated by the NPYR1-TRPC3-ET1 signaling axis in cerebrovascular endothelial cells, and demonstrate that disruption of this signaling axis can reduce the susceptibility to seizures and their deleterious consequences. Results from this study will reveal new mechanistic insights regarding IHR and may lead to new treatments for epilepsy and other neurological diseases.

PI_NAMEs: ZHENG, FANG  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Acute;Address;Adrenergic Agents;Aging;Agonist;antagonist;Anticonvulsants;Area;arteriole;Astrocytes;awake;Binding;Blood flow;Blood Glucose;Blood Vessels;Brain;Brain Injuries;Cations;cell type;Cells;Cephalic;cerebral artery;cerebrovascular;Cerebrovascular Circulation;cerebrovascular reactivity;Cerebrum;Clinical;constriction;Consumption;Core-Binding Factor;Coupling;Data;Electroencephalography;Endothelial Cells;Endothelin A Receptor;Endothelin Receptor;Endothelin-1;Endothelium;Epilepsy;Event;experimental study;Functional disorder;Functional impairment;gamma-Aminobutyric Acid;genetic approach;Harvest;hemodynamics;improved;in vivo;inhibitor;insight;Interneurons;Knock-out;Knockout Mice;Laser Speckle Imaging;Mediating;Modeling;Molecular Target;Monitor;Mus;Muscle Cells;Nerve Degeneration;Nervous System Disorder;neuroinflammation;Neurological outcome;neuronal metabolism;Neurons;neuropeptide Y;Neuropeptide Y Receptor;neurovascular coupling;neurovascular unit;novel;Oxygen;parenchymal arterioles;Pathogenicity;Pathologic;Pharmaceutical Preparations;pharmacologic;Pilocarpine;Play;Predisposition;Preparation;Process;receptor;Regional Blood Flow;Research;response;Role;Seizures;Signal Pathway;Signal Transduction;Smooth Muscle Myocytes;Status Epilepticus;Testing;Tissues;Traumatic Brain Injury;TRP channel;Vascular Smooth Muscle;vasoconstriction;Vasoconstrictor Agents;Vasodilation;Vasodilator Agents

PROJECT_TITLE: The role of the endothelial NPYR1-TRPC3-ET1 signaling axis in neurovascular coupling dysfunction

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


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

ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: NARRATIVE This application investigates the feasibility of a new way to interrupt an intracellular infection, using a chemical that damages the bacterial inner membrane. The larger significance of these efforts is their potential to reveal new approach(es) for addressing the growing problem of untreatable bacterial infections.

PI_NAMEs: DETWEILER, CORRELLA S (contact)

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: Address;Affect;Animals;Bacteria;Bacterial Infections;Binding;Biological;biological adaptation to stress;Cell Culture Techniques;cell injury;Cell membrane;Cell Membrane Permeability;Cells;Cellular biology;Chemicals;Cholesterol;Colony-forming units;CRISPR interference;Cytolysis;Data;Dose;efflux pump;Escherichia coli;experimental study;Female;Future;Genes;Genetic;Gram-Negative Bacteria;Growth;high reward;high risk;in vivo evaluation;Infection;inhibitor;innovation;Interruption;Ions;knock-down;Lead;Lipid Bilayers;Lipids;Liver;Macrophage;Macrophage Cell Biology;male;Mammalian Cell;Membrane;Membrane Proteins;Methods;Microscopy;Modification;Mus;mutant;nanomolar;Natural Immunity;Nature;novel strategies;pathogen;Pathogenesis;Pathogenicity;Pathway interactions;Peptides;Permeability;Phagosomes;Polymyxin B;Process;Propidium Diiodide;Proteins;Protons;Publishing;Resistance;Salmonella;Salmonella typhimurium;sex;small molecule;Spleen;Testing;tool;Toxic effect;transcriptomics;Vesicle;Virulence;voltage;Work

PROJECT_TITLE: Using Salmonella Pathogenesis and Cell Biology as a Discovery Tool

STUDY_SECTION: DDR

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


NIH_SPENDING_CATS: Asthma;Genetics;Human Genome;Lung

ORG_CITY: DENVER

ORG_NAME: NATIONAL JEWISH HEALTH

PHR: Asthma afflicts over 10 million people in the USA in association with greater than $25 billion in yearly health care costs. Inhaled glucocorticoids fail to control symptoms in some patients. By exploring the molecular pathways induced by glucocorticoids, we will uncover newer and safer targets for better treatment of asthma.

PI_NAMEs: GERBER, ANTHONY N (contact)

PROGRAM_OFFICER_NAME: LU, JINING

PROJECT_TERMS: Address;Advanced Development;American;analysis pipeline;Anti-Inflammatory Agents;Applications Grants;Asthma;asthma exacerbation;asthmatic patient;Binding;Biochemical;Bioinformatics;Biological Assay;cell type;Cells;ChIP-seq;Chromatin;Chromatin Loop;chromosome conformation capture;Clinical;Complex;cytokine;Data;Data Set;Disease;DNA;DNA Sequence;Enhancers;Exhibits;Family;Functional disorder;Gene Expression;Gene Expression Regulation;gene induction;Genes;Genetic;genetic association;genetic signature;Genetic Transcription;genome-wide;Genomic approach;genomic signature;Genomics;Glucocorticoid Receptor;Glucocorticoids;glycosyltransferase;Goals;Health Care Costs;Human;Immune;Immunomodulators;improved;Infection;Inflammation;Inflammatory;Inhalation;knock-down;Knowledge;Ligand Binding;Ligands;Link;Lung;Maps;Mediating;member;Methods;Modeling;Molecular;Molecular Conformation;Muscle function;NF-kappa B;novel;novel therapeutics;Odds Ratio;Pathogenesis;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Pharmacogenomics;pharmacologic;promoter;receptor;receptor binding;Receptor Signaling;Regulation;Reporter;Repression;Research;respiratory smooth muscle;response;Response Elements;Risk;RNA;side effect;Signal Pathway;Signal Transduction;Single Nucleotide Polymorphism;Site;Slice;Small Interfering RNA;Steroids;Symptoms;Systemic Therapy;Testing;Therapeutic;Therapeutic Effect;therapeutic evaluation;Tissues;Transcript;transcription factor;Transcriptional Regulation;translational approach;translational model;Viral;virtual

PROJECT_TITLE: Mechanisms and Consequences of Gene Induction by Glucocorticoids in Airway Smooth Muscle

STUDY_SECTION: LCMI

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


ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: PROJECT NARARATIVE Many tumors have been sequenced, providing lists of mutations that commonly occur and likely drive disease. However, the precise role of most mutations is unknown, and some may play different roles according to the cell type they occur in or the presence of other mutations. We present BEAT-seq, a technology for engineering many mutations in parallel into cells and observing how gene expression is altered in response. Their effects can therefore be compared, for example enabling function to be assigned to mutations with unknown roles.

PI_NAMEs: LOWE, SCOTT W.;NORMAN, THOMAS MAXWELL (contact)

PROGRAM_OFFICER_NAME: LI, JERRY

PROJECT_TERMS: Address;Affect;Alleles;Attention;base editing;base editor;Bayesian Method;Behavior;behavior change;Biological;Biological Assay;Calibration;cancer genetics;Catalogs;Cell Line;Cell Transplantation;cell type;Cells;clinical phenotype;clinical sequencing;Clustered Regularly Interspaced Short Palindromic Repeats;Credentialing;CRISPR screen;Data;design;Development;Disease;Engineering;Environment;Epithelial Cells;Evolution;Exhibits;Experimental Designs;experimental study;fitness;flexibility;functional genomics;Gene Expression;Genes;Genetic;Genetic Diseases;genetic variant;Germ-Line Mutation;Goals;Immune system;improved;In Vitro;in vivo;insight;KRAS2 gene;Learning;Libraries;Lung;Malignant Neoplasms;Measures;Mediating;Methods;Modeling;molecular phenotype;Morphologic artifacts;Mus;mutant;Mutation;Oncogenic;Pancreas;parallelization;Phenotype;Play;Population;Procedures;Protocols documentation;rare variant;Recurrence;Reproducibility;response;Role;sensor;single-cell RNA sequencing;Somatic Mutation;Statistical Models;Tail;targeted sequencing;Techniques;Technology;Tissues;tool;TP53 gene;transcriptome;transcriptome sequencing;Transplantation;treatment response;tumor;tumor microenvironment;Variant;variant detection;variant of unknown significance;Work

PROJECT_TITLE: Systematic characterization of cancer variants using single-cell functional genomics


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Dissemination and Implementation Research;Health Services;Neurodegenerative;Neurosciences;Palliative Care;Primary Health Care

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: PROJECT NARRATIVE The ENgaging in Advance Care planning Talks (ENACT) Group Visits intervention is a theory-based and practical primary care model that uses the strengths of group visits to promote advance care planning discussions and documentation. This effectiveness study will provide evidence for use of this advance care planning intervention among older adults with and without early Alzheimer's dementia. Specifically, ENACT Group Visits intervention may improve patient-centered care by increasing advance care planning documentation, advance care planning readiness, decision self-efficacy, and quality of communication related to decision making about care preferences.

PI_NAMEs: LUM, HILLARY  (contact)

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: acceptability and feasibility;Address;Advance Care Planning;advanced directive;Affect;Age;Age Years;Alzheimer's Disease;Alzheimer's disease related dementia;Anxiety;arm;care preference;Caring;Characteristics;Clinic;cognitive function;cognitive load;Communication;Communities;comparison control;Data;Decision Making;decision-making capacity;Dementia;design;Diagnosis;Disease Management;Documentation;Effectiveness;effectiveness evaluation;effectiveness study;effectiveness testing;effectiveness trial;end of life care;evidence base;experience;family support;Focus Groups;Future;Goals;Health Promotion;Hospitalization;Impaired cognition;Impairment;implementation measures;implementation outcomes;implementation strategy;implementation study;improved;Individual;Intervention;intervention effect;Interview;Learning;Life;Measures;Mechanical ventilation;Medical;Methods;mild cognitive impairment;Modeling;nutrition;older adult;Outcome;Patient Preferences;Patient-Centered Care;Patients;Persons;Physicians;Pilot Projects;pragmatic implementation;preference;Prevalence;Primary Care;primary care clinic;primary care patient;primary care setting;primary outcome;Process;programs;Provider;Quality of life;Randomized;randomized trial;Readiness;Reporting;Research Proposals;Sampling;secondary outcome;Self Efficacy;Social Workers;Testing;theories;therapy design;Time;Translational Research;treatment arm;United States National Institutes of Health;Video Recording;Visit

PROJECT_TITLE: Effectiveness of Engaging in Advance Care Planning Talks (ENACT) Group Visits Intervention in Primary Care for Older Adults with and without Alzheimer's Dementia

STUDY_SECTION: CMPC

STUDY_SECTION_NAME: Clinical Management of Patients in Community-based Settings Study Section[CMPC]