NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE The proposed research project is aimed at elucidating the role of RNA and RNA-binding proteins (RBPs) in regulating histone deacetylase (HDAC) recruitment to gene targets. This molecular understanding has the potential to identify highly precise therapeutic targets for inhibition of HDACs in cancers where HDACs are overrepresented. Thus, the proposed work is relevant to the NIH mission of health as it could lead to improved cancer treatments with fewer side effects.

PI_NAMEs: GUO, JAMES KANG (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Affinity Chromatography;Anti-sense RNA;Binding;Binding Proteins;Binding Sites;cancer therapy;cancer type;Cancerous;Cell Cycle;Cell Nucleus;Cells;Chromatin;chromatin modification;Complex;crosslink;Data;DNA Binding;DNA-Binding Proteins;effective therapy;Enzymes;experimental study;Future;Gene Expression;Gene Expression Regulation;gene repression;Gene Silencing;Gene Targeting;Genes;Genetic;genetic manipulation;genetic regulatory protein;Genome;genomic locus;Guide RNA;HDAC1 gene;HDAC3 gene;Health;Histone Deacetylase;Histone Deacetylase Inhibitor;Histone Deacetylation;Human;Immunoprecipitation;improved;in vivo;inhibitor;Knock-out;Link;link protein;Malignant Neoplasms;Mass Spectrum Analysis;Measures;Mediating;Methods;Mission;Molecular;mRNA Precursor;Multiprotein Complexes;Mutate;novel;Nuclear;Pathology;Patients;Pharmaceutical Preparations;pharmacologic;protein complex;Protein Isoforms;Proteins;public database;recruit;Repression;Research;Research Project Grants;RNA;RNA Binding;RNA-Binding Proteins;Role;side effect;Site;Specificity;Suppressor-Effector T-Lymphocytes;Testing;Therapeutic;therapeutic target;Time;Toxic effect;transcription factor;tumor;Tumor Suppressor Genes;United States National Institutes of Health;Untranslated RNA;Work;X Chromosome

PROJECT_TITLE: Characterizing the RNA-mediated recruitment of histone deacetylases to chromatin

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


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Aging;Cancer;Cancer Genomics;Genetics;Human Genome;Prostate Cancer;Urologic Diseases

ORG_CITY: NEW YORK

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative  The Administrative and Data Management Core will provide coordination and oversight of all activities of the Projects and Cores in this Program, will maximize interactions and potential synergies among Project Leaders, Core Leaders, and the laboratories, and will foster the sharing of data and resources among Project investigators and with the external community.

PI_NAMEs: SHEN, MICHAEL M. (contact)

PROJECT_TERMS: Abate;Area;Bass;Biometry;Budgets;Cancer Center;Cells;Collaborations;Communication;Communities;Complex;conflict resolution;Dana-Farber Cancer Institute;Data;data management;data sharing;Ensure;Equity;Evaluation;experience;Feedback;Fostering;Future;Genetically Engineered Mouse;genomic data;Genomics;Health;Human Resources;Individual;Infrastructure;Institution;Laboratories;laboratory experiment;Laboratory Personnel;Leadership;Malignant neoplasm of prostate;Medical center;Medicine;meetings;member;Memorial Sloan-Kettering Cancer Center;Mission;Modeling;Molecular Analysis;Monitor;Mouse Strains;Office of Administrative Management;operation;Oregon;Organization administrative structures;Organoids;Participant;Pharmacologic Substance;Preparation;Program Reviews;programs;Progress Reports;recruit;Research;Research Personnel;Resolution;Resource Sharing;Resources;Science;Scientist;single cell sequencing;Structure;success;synergism;The Jackson Laboratory;Time;Universities

PROJECT_TITLE: Core B: Administrative and Data Management Core


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Cardiovascular;Clinical Research;Genetics;Heart Disease;Immunotherapy

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Narrative Immune checkpoint inhibitors (ICI) have transformed cancer treatment, but may cause cardiac inflammation (or myocarditis) which may lead be serious and even fatal. We propose to study the underlying mechanisms of ICI-associated heart damage, specifically studying the role that specific immune cell populations play in driving this fulminant complication. This study will provide significant insights into the biological basis of ICI- cardiovascular toxicities and enable more effective screening and treatment strategies.

PI_NAMEs: BALKO, JUSTIN M (contact);MOSLEHI, JAVID J

PROGRAM_OFFICER_NAME: DESVIGNE-NICKENS, PATRICE

PROJECT_TERMS: Ablation;Adoptive Transfer;Affect;Aftercare;Antigen Targeting;Antigens;Arrhythmia;Attenuated;Autoimmune;Autoimmunity;Automobile Driving;Benefits and Risks;Biological;Biological Markers;Blocking Antibodies;Body System;cancer immunotherapy;cancer therapy;cancer type;Cardiac;Cardiology;Cardiovascular Diseases;Cardiovascular system;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Line;Cells;Cessation of life;checkpoint therapy;Clinical;Complication;CTLA4 blockade;CTLA4 gene;cytotoxic CD8 T cells;Data;Death Rate;Development;early onset;effective therapy;Etiology;Event;experience;experimental study;Fatality rate;Functional disorder;Genes;Genetic;Grant;Heart;heart damage;Human;human tissue;Immune;immune cell infiltrate;Immune checkpoint inhibitor;Immune system;Immune Targeting;immune-related adverse events;Immunologics;Immunologist;Immunology;Immunotherapy;improved;Infiltration;Inflammatory;insight;International;Interruption;Lead;Ligands;Macrophage;Malignant Neoplasms;Modeling;Monoclonal Antibodies;mouse model;Mus;Muscle;Muscle Cells;Myelogenous;Myocardial;Myocarditis;Myocardium;Myositis;new technology;Oncologist;Oncology;Pathogenesis;Pathogenicity;Pathologic;Pathology;Patients;PDL1 pathway;peripheral tolerance;Phenocopy;Phenotype;Play;Population;pre-clinical;Pre-Clinical Model;Prevention strategy;programmed cell death ligand 1;programmed cell death protein 1;receptor;Receptor Activation;reconstitution;response;restraint;Risk Management;Role;Sampling;Scientist;screening;Self Tolerance;side effect;single cell technology;single-cell RNA sequencing;Skeletal Muscle;Specimen;Striated Muscles;success;systemic autoimmunity;T cell infiltration;T-Lymphocyte;Testing;Therapeutic;Thymus Gland;Tissue Banks;Toxic effect;Transcript;Translating;treatment strategy;Wild Type Mouse

PROJECT_TITLE: Immunologic and Antigenic Drivers of Immune Checkpoint Inhibitor-Associated Myocarditis

STUDY_SECTION: AICS

STUDY_SECTION_NAME: Atherosclerosis and Inflammation of the Cardiovascular System Study Section[AICS]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Clinical Research;Genetics;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Pediatric;Pediatric - AIDS;Social Determinants of Health

ORG_CITY: PROVIDENCE

ORG_NAME: MIRIAM HOSPITAL

ORG_STATE: RI

PHR: PROJECT NARRATIVE This study will investigate existing knowledge gaps related to the development of drug resistance to common medications for HIV among a large, well-characterized cohort of children and adolescents living with HIV in western Kenya. The proposed research is highly relevant to public health since it will fill knowledge gaps in the scientific literature, which will lead to better interpretation of drug resistance tests in this population, improve clinical management and reduce HIV-related sickness and death. The long-term goal of this research is to provide evidence to improve clinical guidelines and disease management for children and adolescents living with HIV in resource-limited settings.

PI_NAMEs: KANTOR, RAMI  (contact);VREEMAN, RACHEL CHRISTINE

PROGRAM_OFFICER_NAME: CRAWFORD, KEITH W

PROJECT_TERMS: acquired drug resistance;Address;Adherence;Adolescent;Adult;Affect;Africa South of the Sahara;Anti-Retroviral Agents;antiretroviral therapy;Archives;Biological Assay;Blood specimen;Cessation of life;Child;Clinical;Clinical Management;clinically significant;cohort;Cohort Studies;Collaborations;design;Developed Countries;Disease Management;DNA;Drug resistance;drug resistance development;eligible participant;Enrollment;Etiology;Evaluation;Failure;Formulation;Funding;Genetic Polymorphism;Genotype;Goals;Guidelines;health care availability;HIV;HIV drug resistance;HIV Genome;HIV-1;HIV-1 drug resistance;HIV-infected adolescents;improved;In Vitro;innovation;Investigation;Kenya;Knowledge;Length;Literature;Minority;Modeling;Monitor;Morbidity - disease rate;mortality;Mutation;next generation sequencing;novel;Outcome;Participant;Patient Care;Perinatal;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Population;Positioning Attribute;Predisposition;programs;Public Health;Recommendation;Regimen;Research;Research Design;Resistance;resistance mechanism;Resource-limited setting;Resources;RNA;Sampling;success;Testing;Therapeutic;therapy adherence;therapy resistant;transmission process;Treatment Failure;treatment optimization;Treatment outcome;United States National Institutes of Health;Variant;Vulnerable Populations;Work

PROJECT_TITLE: Addressing HIV drug resistance research gaps in a cohort of perinatally infected Kenyan children and adolescents


NIH_SPENDING_CATS: Aging;Bioengineering;Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Prostate Cancer;Urologic Diseases

PHR: Project Narrative  The Pathobiology Core A will provide all Program investigators multiple pathology services. Core A is essential for the success of all projects via the expertise provided in pathological characterization of mouse and annotated human tissue. Further, Core A will provide expertise in generation and use of 3-dimensional organotypic and organoid models, performing scRNASeq experiments in highly annotated human tissue and sophisticated imaging for in situ localization of antibodies and genes discovered.

PI_NAMEs: LODA, MASSIMO  (contact)

PROJECT_TERMS: 3-Dimensional;Antibodies;arm;Biological Assay;Biopsy Specimen;bone;Castration;Cells;cellular imaging;Clinical;Collaborations;Collection;Complex;Computing Methodologies;Data;Development;Disease;Disease Resistance;Epithelium;Evaluation;experimental study;Freezing;gene discovery;Generations;Genetic;Genetic Recombination;Genetically Engineered Mouse;Genotype;Goals;Human;human tissue;Image;imaging platform;Immune;Immunofluorescence Immunologic;improved;In Situ;in situ imaging;Inflammatory Infiltrate;innovation;laser capture microdissection;Link;Malignant neoplasm of prostate;Malignant Neoplasms;Metastatic Neoplasm to the Bone;Microscopic;Modality;Modeling;Molecular;Molecular Analysis;molecular pathology;mouse model;multidisciplinary;Mus;Neoplasm Metastasis;neoplastic cell;Neuroendocrine Tumors;new technology;novel;novel strategies;nucleic acid quantitation;Organoids;Outcome;Paraffin Tissue;Pathologic;Pathology;Patients;Performance;Phenotype;programs;Prostate;Prostatic;Proteins;Radical Prostatectomy;Research Personnel;Research Project Grants;Resistance;Resources;Role;Sampling;Series;Services;Signal Transduction;single cell analysis;single cell sequencing;single-cell RNA sequencing;Slice;Specimen;Stains;success;Systems Analysis;Techniques;Technology;therapy resistant;Tissue imaging;Tissue Microarray;Tissue Sample;Tissues;tool;transcriptomics;tumor;tumor heterogeneity;tumor progression;Validation

PROJECT_TITLE: Core A: Pathobiology Core


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Clinical Research;Genetics;Human Genome

ORG_CITY: LA JOLLA

ORG_NAME: LA JOLLA INSTITUTE FOR IMMUNOLOGY

ORG_STATE: CA

PHR: Narrative We need to understand how differences in our genomes, coupled with environmental factors, translate into changes in specific biological processes to explain the vastly different outcomes among individuals when faced with an infection or in terms of their disease risk for having autoimmune conditions or cancer. However, human genome is complex even when studied as a linear DNA sequence and its three-dimensional folding, which itself is impacted by differences in this sequence, adds another layer of complexity to interpreting how cells utilize over a million different control switches to orchestrate a specific gene expression program that is precise yet flexible. This project uses human immune cells to study how differences in genome sequence lead to changes in genome function, and in turn disease risk and outcome, through calibrating genome’s three-dimensional organization.

PI_NAMEs: AY, FERHAT  (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: 3-Dimensional;Address;Alleles;Autoimmune Diseases;Biological;Biological Assay;Biological Process;Calibration;causal variant;cell type;Cells;Chromatin Loop;comparative;Complex;Computer Analysis;Computing Methodologies;Coupled;Data;Dimensions;Disease;Disease Outcome;disorder risk;DNA Sequence;Environmental Risk Factor;flexibility;Gene Expression;Gene Expression Regulation;genetic variant;Genetic Variation;Genome;genome wide association study;genome-wide analysis;Genomic Segment;Genotype;Goals;Human;Human Genetics;Human Genome;Immune;Individual;Infection;Knowledge;Lead;Malignant Neoplasms;Maps;Measurable;method development;Methods;Mind;Modality;Molecular;Molecular Conformation;Outcome;Phenotype;programs;Regulatory Element;Rejuvenation;Research Personnel;Resolution;Role;Specificity;Techniques;Translating;Variant

PROJECT_TITLE: Studying the function of human genetic variation in the light of 3D genome organization

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


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: CAMBRIDGE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: PROJECT NARRATIVE Chromatin - the physiological form of our genomes - is composed of histone proteins and DNA. Chemical modifications of histones and the factors that do so play essential roles in the cell. This project focuses on how chromatin adaptor proteins help decode this chemical language and how they regulate gene expression. These studies will improve our understanding of how protein complexes assemble on chromatin and how disruption of these basic mechanisms lead to disease.

PI_NAMEs: SOTO-FELICIANO, YADIRA M (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Adaptor Signaling Protein;Affect;Alleles;Autoimmunity;Award;Bar Codes;Binding;Biochemical;Biochemistry;Biological;Biological Assay;Biology;career;Cell Physiology;Cells;Chemicals;ChIP-seq;Chromatin;chromatin protein;Chromatin Remodeling Factor;Chromatin Structure;Clustered Regularly Interspaced Short Palindromic Repeats;combinatorial;Communities;Complex;Data;Development;Disease;Distal;DNA;DNA Binding;DNA Integration;Endocrine;Enhancers;Environment;Epigenetic Process;epigenomics;Event;Exclusion;Functional disorder;functional genomics;Future;Gene Expression;Gene Expression Profiling;Genes;genetic approach;Genetic Transcription;Genome;genome-wide;Genomic approach;genomic locus;Genomics;histone methyltransferase;histone modification;Histones;human disease;Impairment;improved;In Situ;innovation;insight;Intellectual functioning disability;Intercistronic Region;interest;Knowledge;Label;Language;Lead;leukemia;Libraries;Malignant Neoplasms;Mediating;Menin;Mentors;Methods;Methyltransferase;MLL gene;Modification;Molecular;Motivation;mutant;Mutation;novel;Nucleosomes;Oncogenic;Output;Phase;Phenotype;Physiological;Physiology;Play;pleiotropism;Positioning Attribute;Post-Translational Protein Processing;Process;Proliferating;promoter;protein complex;protein structure;Proteins;Proteomics;Reader;Reading;recruit;Recurrence;Regulation;Regulatory Element;Research;Resources;Role;scaffold;Scaffolding Protein;Shapes;Signal Transduction;Site;structural biology;Surface;Testing;Tissues;Training;transcription factor;Transcriptional Regulation;tumor;Work

PROJECT_TITLE: Understanding mechanisms of transcriptional regulation by chromatin adaptor proteins

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ED_INST_TYPE: SCHOOLS OF MEDICINE

ORG_CITY: MINNEAPOLIS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE This proposal will determine the importance of hybrid peptide specific T cells for the breakdown of immunological tolerance and initiation of autoimmune type 1 diabetes. The goals of this proposal are to determine if HP-specific CD4+ T cells initiate T1D and if targeting them can lead to tolerance as a prevention or cure for T1D. The second goal of the grant is to develop a gene signature from known pathogenic cells in NOD mice and identify the same subset in human T1D patients. Completion of this project could lead to better biomarkers to predict T1D risk and disease progression.

PI_NAMEs: FIFE, BRIAN T (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: anergy;Antibodies;antigen test;antigen-specific T cells;Antigens;Autoantibodies;Autoimmune;Autoimmune Diabetes;Autoimmune Diseases;autoreactivity;B-Lymphocytes;Beta Cell;Biological Markers;Blocking Antibodies;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Death;Cell Separation;Cells;central tolerance;chimeric antigen receptor;Coupled;Development;Diabetes Mellitus;Diabetes prevention;diabetes risk;diabetic;Diabetic mouse;Disease Progression;Early Diagnosis;effective therapy;Fingerprint;Frequencies;Functional disorder;Gene Expression Profile;genetic signature;Genetic Transcription;Goals;Grant;Human;Hybrids;Immune Tolerance;In Vitro;Inbred NOD Mice;Individual;Insulin;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;islet;islet cell antibody;Knowledge;Mediating;memory CD4 T lymphocyte;Modeling;mouse model;Mouse Strains;Mus;neoantigens;Non obese;novel therapeutic intervention;Onset of illness;Pancreas;Pathogenesis;Pathogenicity;Pathway Analysis;Patients;Peptides;Peripheral;Population;Predisposition;prevent;Prevention;Preventive therapy;Production;programs;Property;Proteins;Protocols documentation;Reagent;Regulatory T-Lymphocyte;Research;Risk;Role;screening;single-cell RNA sequencing;T cell differentiation;T cell regulation;T-Cell Receptor;T-Lymphocyte;targeted treatment;Testing;trafficking;transcriptome;type I diabetic

PROJECT_TITLE: Identifying and preventing antigen specific T cells in diabetes

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Cardiovascular;Clinical Research;Estrogen;Hematology;Mental Health;Suicide;Women's Health Research

ORG_CITY: ATLANTA

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE The purpose of this study is to determine whether transgender people have higher or lower risk of certain diseases than men and women in the general population. Many transgender people require extensive treatment of hormones. The study will also compare results of different hormone treatments with regards to complications and other health problems.

PI_NAMEs: GOODMAN, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Acute;age group;age related;American;Androgen Antagonists;Area;Benefits and Risks;Birth;Blood;Blood Pressure;Body mass index;Bone Density;California;Cardiovascular Diseases;Cardiovascular system;cis-female;cis-male;cisgender;Clinical;clinical practice;cohort;Cohort Studies;Computerized Medical Record;Data;Data Analyses;Data Collection;Dementia;Development;Diagnosis;Disease;dosage;Dose;Drug Combinations;Electronics;Endocrine;Endocrinology;Enrollment;Enzymes;Epidemiology;Estrogens;Ethnic Origin;Event;experience;Feeling suicidal;Female;follow-up;Gender;gender affirming care;gender affirming hormone therapy;gender affirming therapy;gender nonconforming;General Population;Geography;Goals;Gonadal Steroid Hormones;Guidelines;Health;Health Status;Healthcare;Hematocrit procedure;Hematology;High Prevalence;hormone therapy;Hormones;Hospitalization;Incidence;indexing;Individual;Integrated Health Care Systems;Internal Medicine;Ischemic Stroke;Journals;Knowledge;Laboratories;Lipids;Liver;Longitudinal cohort;Longitudinal Studies;male;Measures;member;men;Mental Health;Metabolic;Methods;Monitor;Neurosciences;NIH Program Announcements;Oral;Outcome;Participant;Pattern;Persons;Pharmaceutical Preparations;Pharmacoepidemiology;Polypharmacy;Population;Preventive Medicine;Progesterone;Publications;Publishing;Race;Recommendation;Recording of previous events;Reference Values;Reporting;Research;Resources;Risk;Route;Schedule;Self-Injurious Behavior;Serum;Site;Societies;Suicide attempt;Testosterone;transfeminine;transgender;transmasculine;venous thromboembolism;Woman

PROJECT_TITLE: An expanded national cohort study of transgender people

STUDY_SECTION: CHSB

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology B Study Section[CHSB]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Neurosciences;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SALT LAKE CITY

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Much of human perception and behavior is governed by functioning brain networks. This project will develop a method for generating human cortico-striatal organoids from stem cells and demonstrate that these organoids can be used to model the development of human cortico-striatal networks. The ability to create patient-specific cortico-striatal organoids for use in a variety of laboratory analyses will provide a new approach to enable patient-specific diagnostics and treatments associated with disorders of cortico-striatal connectivity, including autism, schizophrenia, epilepsy, and mood disorders.

PI_NAMEs: SHCHEGLOVITOV, OLEKSANDR  (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: 3-Dimensional;Action Potentials;Address;Affect;Anatomy;Animal Model;Astrocytes;autism spectrum disorder;Behavior;Brain;Brain Diseases;Brain region;brain tissue;Cells;Chronic;Coculture Techniques;Communication;Complex;Corpus striatum structure;Development;Diagnostic;Disease;disease model;drug discovery;Electrodes;Electrophysiology (science);Epilepsy;excitatory neuron;Exhibits;experimental study;Functional impairment;Genetic Materials;Human;human model;human stem cell-derived;human stem cells;Huntington Disease;Immunohistochemistry;Implant;inhibitory neuron;innovation;insight;Laboratories;Major Depressive Disorder;Mental disorders;Methods;model development;Modeling;Molecular;Molecular Abnormality;Mood Disorders;Morphology;multi-electrode arrays;nerve stem cell;Nervous System;Nervous System Disorder;neural;neural network;Neurons;novel;novel strategies;novel therapeutics;Oligodendroglia;optogenetics;Organoids;Parkinson Disease;patch clamp;Pathologic;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Perception;Phelan-McDermid syndrome;Phenotype;Physiological;Physiology;Population;precision drugs;prevent;Property;Protocols documentation;Quantitative Reverse Transcriptase PCR;rabies viral tracing;Reproducibility;Schizophrenia;Science;self organization;single cell mRNA sequencing;single-cell RNA sequencing;Slice;stem cell organoids;Synapses;System;system architecture;Techniques;Testing;Time;With laterality;Work

PROJECT_TITLE: Assembly and characterization of human cortico-striatal neural networks


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: BOSTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project narrative Influenza A virus (IAV) is one of the major causes of seasonal influenza, being responsible for an average of 36,000 deaths in the US each year. Despite the fact that variation in glycosylation is a major mechanism whereby the virus escapes immune surveillance, there has been no systematic effort to correlate site-specific IAV glycosylation with viral immunogenicity. In this proposal we will use state-of-the-art mass spectrometry, antigenic cartography, and computer modeling of glycosylated surface antigens from multiple strains of IAV to elucidate this understanding, with the expectation that it will facilitate the development of more effective vaccines.

PI_NAMEs: WAN, XIUFENG HENRY;WOODS, ROBERT J;ZAIA, JOSEPH  (contact)

PROGRAM_OFFICER_NAME: GORDON, JENNIFER L

PROJECT_TERMS: Adaptive Immune System;Address;Affect;Allosteric Site;Amino Acids;Antibodies;Antigenic Variation;Antigens;Appearance;Attenuated;Avidity;Binding;Binding Sites;Biological Assay;Cessation of life;Communities;Complex;Computer Models;Consensus Sequence;Data;Development;Epitopes;Escape Mutant;Evolution;expectation;fitness;Genes;Genetic;Genomics;Glycoproteins;glycoproteomics;glycosylation;Goals;Head;Hemagglutinin;Human;Hybrids;Immune;Immune response;Immunity;Immunodominant Epitopes;immunogenic;immunogenicity;Immunologic Surveillance;improved;Influenza A virus;Influenza A Virus, H1N1 Subtype;influenza virus strain;influenza virus vaccine;influenzavirus;Knowledge;Lectin;Link;Mannose;Mass Spectrum Analysis;Measures;Membrane Glycoproteins;model building;Modeling;molecular dynamics;molecular modeling;Mus;mutant;Mutation;Natural History;Natural Immunity;Neuraminidase;neutralizing antibody;neutralizing vaccine;Outcome;pandemic disease;Pattern;Polymerase;Polysaccharides;Population;population based;Population Heterogeneity;Positioning Attribute;Preparation;Property;Proteins;Proteome;Proteomics;rational design;receptor;receptor binding;Recombinant Vaccines;Recombinants;Research;response;seasonal influenza;Seasons;sialic acid receptor;Site;Specificity;stem;Structure;Surface Antigens;universal influenza vaccine;Use Effectiveness;Vaccine Design;vaccine effectiveness;vaccine response;Vaccines;Variant;Viral;viral fitness;Virus;Work

PROJECT_TITLE: Selecting HA glycosylation for improved vaccine responses

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


ADMINISTERING_IC: DK

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Crohn's Disease;Digestive Diseases;Infectious Diseases;Inflammatory Bowel Disease

ORG_CITY: CLEVELAND

ORG_DEPT: PATHOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE Some patients with Crohn Disease have a yeast called Debaryomyces hansenii present within their ulcers, and mouse models of intestinal injury show that this yeast impairs intestinal healing. The research described here will help understand the mechanisms through which this yeast persists within the intestine and how it blocks injury repair. This project will increase our understanding of how microbes that are associated with Crohn Disease can affect disease course, with the goal of identifying new targets for future therapeutic development to benefit Crohn Disease patients with D. hansenii infection.

PI_NAMEs: NEWHALL, KEVIN PRESCOTT (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: Adopted;Affect;antagonist;Automobile Driving;Biopsy;Bone Marrow;Candida albicans;Cell Line;cell type;Cells;Chemicals;Chronic;chronic infection;chronic inflammatory disease;Colon;Crohn's disease;cytokine;Cytology;Data;data visualization;Disease;Disparity;Effector Cell;Event;fitness;Food Additives;Future;Genetic Screening;Germination;Goals;gut microbiome;healing;Histoplasmosis;Hyphae;Immune Evasion;Immune response;immunopathology;Impaired wound healing;Impairment;In Vitro;in vivo;in vivo Model;Individual;Infection;Inflammatory;Injury;injury and repair;Interferon Type I;intestinal injury;Intestines;Macrophage;Macrophage Activation;Mechanics;member;Methods;Microbe;microbial;microorganism;Modeling;Molecular;Morphology;mouse model;Mucous Membrane;Mus;mutant;Mycoses;new therapeutic target;pathogen;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Pattern recognition receptor;Phagocytosis;Phagolysosome;Phase;Phenotype;Play;Predisposition;Production;RANTES;repaired;Reproduction spores;Research;response;Role;Signal Transduction;Signaling Molecule;Stains;Stress;Testing;therapeutic development;Tissues;TNF gene;Transmission Electron Microscopy;Tuberculosis;Ulcer;Variant;Work;wound healing;Yeasts

PROJECT_TITLE: Microbe dependent mechanisms that antagonize intestinal injury repair


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Hematology;Human Genome;Immunotherapy;Lymphatic Research;Lymphoma;Neurosciences;Orphan Drug;Prevention;Rare Diseases

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE Human T cells that have been engineered with receptors called CARs have been very effective in leukemia and lymphoma, but frequently cause severe side effects called cytokine release syndrome and neurologic symptoms. We aim to prevent these side effects by giving a drug called anakinra, which blocks an immune cell product called interleukin-1, because we think that the interleukin-1 drives a lot of the side effects but is not necessary for the anti-tumor effects of the CAR T cells. In this proposal, we will analyze the data from our clinical trial to see the anakinra worked to decrease the side effects, and we will measure the levels of molecules related to interleukin-1 in the blood and the spinal fluid around the brain; these measurements will enable us to map the relationships among immune cells and understandt what drives the side effects of CAR T cell therapy.

PI_NAMEs: MAUS, MARCELA VALDERRAMA (contact)

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: abstracting;acute toxicity;Adult;anakinra;antitumor effect;Aphasia;Ataxia;Autologous;B-Cell Lymphomas;Blood;Brain;CAR T cell therapy;CD19 Antigens;CD19 gene;CD28 gene;CD3 Antigens;Cell Communication;Cell Compartmentation;Cells;Cerebral Edema;Cerebrospinal Fluid;Childhood Leukemia;Chills;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;Clinical Data;clinical efficacy;Clinical Investigator;Clinical Research;Clinical Trials;Confusion;Correlative Study;cytokine;cytokine release syndrome;Data;Development;Endothelium;Engineering;Event;experience;extracellular;Fc Receptor;FDA approved;Fever;Financial Support;Functional disorder;Funding;Future;Gene Expression Profile;Hallucinations;Human;Hypotension;Hypoxia;Immune;improved;In complete remission;Incidence;Infusion procedures;innovation;Inpatients;Interleukin 6 Receptor;Interleukin-1;Interleukin-1 Receptors;Interleukin-6;Laboratories;Large-Cell Lymphomas;leukemia/lymphoma;Link;Lymphoma;Macrophage activation syndrome;Maps;Measurement;Measures;Mediating;Methods;monocyte;mouse model;Myeloid Cells;Neurologic;Neurologic Symptoms;Neurological outcome;neurotoxicity;Non-Hodgkin's Lymphoma;objective response rate;open label;Outpatients;Participant;Pathogenicity;patient population;Patients;Penetration;peripheral blood;Pharmaceutical Preparations;Phase;Phenotype;Play;prevent;Production;Proliferating;prophylactic;Prophylactic treatment;Proteins;receptor;Receptor Signaling;Refractory;Relapse;Research Personnel;response;Role;Safety;Sampling;Seizures;Sepsis;Severities;side effect;Signal Transduction;single-cell RNA sequencing;Specificity;Steroids;Stupor;success;Symptoms;System;T-Lymphocyte;Therapeutic Agents;tocilizumab;Toxic effect;transcriptome;United States National Institutes of Health;Wages;Work

PROJECT_TITLE: Efficacy and immune effects of anakinra prophylaxis for neurologic toxicity and cytokine release syndrome in patients with lymphoma receiving axicabtagene ciloleucel

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: NARRATIVE The latent viral reservoir in CD4+ T lymphocytes is the barrier to cure and remains to be fully characterized. In this proposal, we will utilize state-of-the-art multi-omics technologies to define the heterogeneity of the viral reservoir in both SIV-infected rhesus monkeys and in HIV-1-infected humans.

PI_NAMEs: BAROUCH, DAN H. (contact);SHALEK, ALEX K

PROGRAM_OFFICER_NAME: REFSLAND, ERIC WILLIAM

PROJECT_TERMS: Affinity;Agonist;Anatomy;Animals;Antibodies;Autopsy;Biological Assay;Biology;Blood;CD4 Positive T Lymphocytes;cell type;Cells;Classification;Clonality;Collaborations;Color;Communities;computer framework;Data;Dissociation;DNA;DNA sequencing;Elements;Fishes;Flow Cytometry;Genome;genome sequencing;genomic profiling;Goals;Hand;Heterogeneity;Histologic;HIV;HIV Genome;HIV-1;Human;Immune mediated destruction;Immunofluorescence Immunologic;Immunotherapeutic agent;Immunotherapy;improved;Individual;Infusion procedures;innovation;Intervention;Israel;Knowledge;Label;Laboratories;Libraries;Location;Macaca mulatta;Massachusetts;Measurement;medical schools;Membrane Proteins;Methodology;Methods;Modality;Molecular;Molecular Profiling;Monkeys;Morphologic artifacts;multiple omics;neutralizing antibody;next generation;Oligonucleotides;Phenotype;Poly A;Population;Predisposition;Prevention;Protocols documentation;receptor;Recording of previous events;reference genome;Reporting;Research;Resolution;RNA;Sampling;Shock;simian human immunodeficiency virus;single cell analysis;single cell genomics;single-cell RNA sequencing;SIV;Specimen;Technology;Tissue Sample;Tissues;TLR7 gene;Transcript;transcriptome;Treatment Efficacy;Vaccination;Viral;viral rebound;Viral reservoir;Virus;Virus Latency;Zambia

PROJECT_TITLE: Single-Cell Analysis of the HIV/SIV Reservoir


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: CAMBERWELL

ORG_COUNTRY: AUSTRALIA

ORG_FIPS: AS

ORG_NAME: KINOXIS THERAPEUTICS PTY LTD

PHR: Application Identifier: 364510 Application Project Title: Advancing KNX100 for the treatment of opioid withdrawal: preclinical efficacy and toxicology, and a phase 1 clinical program. Project Narrative The proposed research program will provide a major advance in public health by delivering a novel treatment for opioid withdrawal symptoms. Opioid addiction currently causes more deaths than car crashes, firearms, or breast cancer in the USA and is a public health issue that must be addressed with the greatest of urgency. Effective management of withdrawal symptoms in patients with opioid use disorders is a key barrier in the successful rehabilitation of such patients and the current research program will accelerate the development of a revolutionary new treatment for this condition.

PI_NAMEs: ALSOP, HUGH WILLIAM (contact);BOWEN, MICHAEL THOMAS;MCGREGOR, IAIN STEWART

PROGRAM_OFFICER_NAME: RAMEY, TANYA S

PROJECT_TERMS: Acceleration;acute symptom;Address;Ames Assay;animal efficacy;Animal Model;Brain;Canis familiaris;Certification;Cessation of life;Clinical;clinical development;Clinical Research;Clinical Trials;comparative;Data;Development;dosage;Dosage Forms;Dose;drug discovery;Drug Kinetics;drug synthesis;efficacy testing;Firearms;first-in-human;Formulation;Funding Opportunities;genotoxicity;Human;human subject;In Vitro;in vivo;Intellectual Property;Investigation;Investigational New Drug Application;Laboratories;Lead;lead candidate;Licensing;lofexidine;Malignant Breast Neoplasm;manufacture;Measures;Micronucleus Tests;Modeling;Mus;National Institute of Drug Abuse;nonhuman primate;novel;novel therapeutics;Opiate Addiction;opioid use disorder;opioid withdrawal;Oral;Outcome;Overdose;Oxytocin;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phase;phase 1 study;Phase I Clinical Trials;Phenotype;Phototoxicity;pre-clinical;pre-Investigational New Drug meeting;preclinical efficacy;prevent;product development;Production;Program Development;programs;Public Health;Rattus;reduce symptoms;Rehabilitation therapy;Research;Rodent;Rodent Model;Safety;safety assessment;safety study;scale up;Severities;Signal Transduction;small molecule;Substance Use Disorder;substance use treatment;System;Testing;Therapeutic;Toxic effect;Toxicology;United States National Institutes of Health;Universities;Vehicle crash;Withdrawal;Withdrawal Symptom


NIH_SPENDING_CATS: Genetics;Human Genome;Kidney Disease;Regenerative Medicine

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE This renewal will expand our investigations of the developmental regulators Pax2 and the related gene Pax8 into adult kidneys, using novel genetic mutations and biochemical methods to define their functions in the inner and outer medulla where regulation of urine concentration occurs. An essential role for Pax genes and proteins in activating and maintaining the expression of urea, water, and ion channels in the collecting ducts of adult kidneys will be examined. Furthermore, cell type specific mutations and single cell analyses will examine how Pax genes contribute to the regeneration of proximal tubule epithelia after acute kidney injury and to promote recovery.

PI_NAMEs: DRESSLER, GREGORY R (contact)

PROGRAM_OFFICER_NAME: BRUNSKILL, ERIC WAYNE

PROJECT_TERMS: Acute;Acute Renal Failure with Renal Papillary Necrosis;Address;Adult;aging population;Animal Model;Area;Automobile Driving;Biochemical;Biochemical Pathway;Biological;Biological Assay;Cell Differentiation process;cell growth;Cell Maintenance;Cell Physiology;Cell Survival;cell type;Cells;Cessation of life;Chemicals;chromatin modification;Chromatin Structure;Chronic;Chronic Kidney Failure;Clinical;clinically significant;cost;Coupled;Data;Development;developmental genetics;Diabetes Mellitus;Disease;DNA Sequence Alteration;Duct (organ) structure;Electrolyte Balance;Epigenetic Process;epigenome;Epithelial Cells;Epithelium;epithelium regeneration;experimental study;Failure;Funding;Genes;Genetic;genetic regulatory protein;Genomics;Goals;Growth;Health;Higher Order Chromatin Structure;Homeostasis;Human;human disease;Hydration status;imprint;inhibitor;Injury;Injury to Kidney;insight;Investigation;Ion Channel;Ischemia;Kidney;kidney cell;Kidney Diseases;Kidney Papilla;Liquid substance;loss of function mutation;Maintenance;mature animal;Mediating;Medicare;Medicine;Methods;Mitosis;mutant;Mutation;Natural regeneration;nephrogenesis;Nephrology;nephrotoxicity;novel;Obesity;Osmolalities;Pathway Analysis;Pathway interactions;Phenotype;Physiological;Physiology;Polycystic Kidney Diseases;Prevalence;protein function;Proteins;Recovery;Regulation;Renal Carcinoma;renal epithelium;repaired;Reperfusion Therapy;Repression;Research Personnel;response to injury;Role;single cell analysis;Site;Sodium Chloride;Specialist;Specific qualifier value;targeted treatment;Tissues;transcriptome;transcriptomics;Translating;Urea;Urine;Water;water channel;whole genome

PROJECT_TITLE: Pax2 Interacting Proteins in Development and Disease

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


NIH_SPENDING_CATS: Biotechnology;Genetics;Neurosciences

ORG_CITY: CHICAGO

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Narrative With this research we hope to untangle the complexities and challenges that have been encountered when trying to correlate the vast number of new mutations in discovered in calcium channel genes in individuals with diverse and overlapping neurological and neuropsychiatric symptoms so we can develop treatments. We will take advantage of a new discovery we have made that these genes produce not one, but two distinct proteins, the calcium channel protein and a new protein called a transcription factor. We will determine how the two proteins function together, how, with different mutations, this cooperation breaks down, and how to develop therapies by correcting the breakdown in integration.

PI_NAMEs: GOMEZ, CHRISTOPHER MANUEL (contact)

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Affect;Antisense Oligonucleotides;Binding;Biological;Calcium Channel;Calcium Signaling;Cell Nucleus;Cell Physiology;Complex;Disease;Epitopes;Genes;Genotype;Human;Impairment;Individual;insight;Internal Ribosome Entry Site;Luciferases;MicroRNAs;Microscopy;Mutation;Neurologic Symptoms;neuron development;Neurons;neuropsychiatric symptom;next generation;novel;Nuclear Translocation;Outcome;Patients;Phenotype;Physiological;Process;protein function;Proteins;Recombinants;Regulation;Reporter;Research;Source;Stimulus;therapy development;transcription factor;Transgenic Mice;Translating;Translations;Viral Vector;Western Blotting

PROJECT_TITLE: Demystifying Disorders of Bicistronic Calcium Channel Genes


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Infectious Diseases;Physical Injury - Accidents and Adverse Effects

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PI_NAMEs: KAGAN, VALERIAN E (contact)

PROGRAM_OFFICER_NAME: WINTERS, THOMAS A

PROJECT_TERMS: Accidents;Aggressive behavior;Anti-Inflammatory Agents;Apoptosis;Apoptotic;Arachidonate 15-Lipoxygenase;Automobile Driving;Bacteria;Biological Markers;Cardiolipins;catalyst;Cell Death;Cell Respiration;Cells;Cessation of life;Complex;cytochrome c;cytokine;Data;design;Disease;drug action;Drug Combinations;Epithelial Cells;Epithelium;Exposure to;Face;Failure;Fatty Acids;Functional disorder;gastrointestinal;gastrointestinal epithelium;Grant;Hematopoietic;Hemeproteins;Imidazole;Immune;immunogenic;Immunosuppression;In Vitro;in vivo;Inflammation;Inflammatory;inflammatory milieu;inhibitor;Injury;intestinal epithelium;Ionizing radiation;Knockout Mice;lipid mediator;lipidomics;Lipids;Lipoxygenase;LOX gene;Macrophage;microbiome components;Mitochondria;Molecular;mortality;Mus;Necrosis;neutrophil;new therapeutic target;next generation;novel;Nuclear Accidents;Occupational Exposure;Organ;oxidation;Oxidation-Reduction;pathogenic bacteria;Pathway interactions;Peroxidases;Pharmacotherapy;Phosphatidylethanolamine;Phosphatidylethanolamine Binding Protein;Phospholipids;Plasma;Production;programs;protein biomarkers;Pseudomonas aeruginosa;Radiation;Radiation Injuries;radiation mitigation;radiation mitigator;Radiation therapy;Radiation Tolerance;Reaction;Resistance;response;Role;Scaffolding Protein;Signal Transduction;Sterility;System;Terrorism;Testing;Theft;therapeutic target;Time;Tissues;Whole-Body Irradiation

PROJECT_TITLE: Selective Inhibitors of Pro-Ferroptotic Lipoxygenases - Next Generation Radiomitigators


ADMINISTERING_IC: AA

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Physical Injury - Accidents and Adverse Effects;Post-Traumatic Stress Disorder (PTSD);Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: SYRACUSE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: SYRACUSE UNIVERSITY

PHR: Project Narrative Sexual minority women (SMW) are at increased risk of engaging in hazardous drinking compared to heterosexual women because of their disproportionate risk of psychosocial stressors, including violence exposure (eg, sexual assault) and sexual orientation-specific minority stressors (eg, homophobic discrimination). Despite the public health necessity of developing effective alcohol treatments for SMW, current alcohol treatment models do not consider unique mental health needs or psychosocial stressors facing this racially diverse, at-risk population. This proposed research aims to use epidemiologic, lab-based, and multi- method longitudinal approaches to develop and test a biopsychosocial model that can both identify SMW subgroups such as SMW of color for targeted prevention efforts and inform effective alcohol interventions for diverse victimized SMW at greatest risk for alcohol use disorders (eg, those engaging in hazardous drinking).

PI_NAMEs: SCHEER, JILLIAN R (contact)

PROGRAM_OFFICER_NAME: RUFFIN, BEVERLY

PROJECT_TERMS: Adult;alcohol abuse therapy;Alcohol consumption;alcohol craving;alcohol intervention;alcohol relapse;alcohol research;alcohol risk;alcohol use disorder;Alcohols;allostatic load;Biological;biological adaptation to stress;biopsychosocial;Cardiovascular system;Chicago;Childhood;Clinical;comorbidity;coping;Discrimination;Doctor of Philosophy;drinking;Ecological momentary assessment;effective therapy;Ensure;Epidemiology;ethnic difference;Ethnic Origin;experience;Exposure to;Face;Galvanic Skin Response;Goals;Growth;hazardous drinking;Health;Heart Rate;heart rate variability;Heterogeneity;Heterosexuals;Homophobia;Hydrocortisone;innovation;Knowledge;Laboratories;Life Experience;life span;Link;Literature;Measurement;men;Mental Health;Mentored Research Scientist Development Award;Mentors;Methods;minority stressor;Modeling;Morbidity - disease rate;National Institute on Alcohol Abuse and Alcoholism;Outcome;Pattern;physical abuse;Physiological;Play;polyvictimization;Population;Populations at Risk;Post-Traumatic Stress Disorders;Prevention;Principal Investigator;Psychophysiology;psychosocial stressors;Public Health;Race;racial difference;racial diversity;Recording of previous events;reduced alcohol use;Reporting;Research;Research Methodology;Research Personnel;Research Priority;Risk;Role;Salivary;Sampling;Scientist;Self Medication;Sex Orientation;Sexual abuse;sexual assault;sexual minority;sexual minority women;sexual victimization;skills;Stigmatization;Stimulus;Stress;stress reactivity;stressor;Subgroup;success;Surveys;Symptoms;System;Testing;theories;Time;tool;Training;treatment adherence;treatment response;Trier Social Stress Test;Universities;Variant;Violence;violence against women;violence exposure;virtual;Woman;women of color;Work

PROJECT_TITLE: Testing a Biopsychosocial Model of Violence Exposure, Minority Stressors, and Hazardous Drinking among Sexual Minority Women

STUDY_SECTION: AA

STUDY_SECTION_NAME: Epidemiology, Prevention and Behavior Research Study Section[AA-2]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE The heart's fibrotic response rapidly progresses heart disease to failure, yet to date effective antifibrotic therapies to manage or reverse fibrosis are lacking. This proposal will investigate the cellular and molecular determinants of the heart's fibrotic responsiveness and define the dynamic processes of key phenotype transitions at the cellular level, which could be leveraged for targeted therapeutic interventions for slowing or reversing fibrosis in the heart and other tissues.

PI_NAMEs: DAVIS, JENNIFER MICHELLE (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Address;Angiotensin II;antifibrotic treatment;Behavior;Cardiac;Cardiac Myocytes;Cells;Chromatin;Chronic;Chronic Disease;Cicatrix;Competence;coronary fibrosis;Cre driver;Cues;Data;Deposition;Development;Disparate;Engineering;Environment;epigenetic memory;Epigenetic Process;experience;experimental study;Exposure to;Extracellular Matrix;Failure;Fibroblasts;Fibrosis;Future;Genetic Transcription;Heart;Heart Diseases;Heart failure;In Vitro;in vivo;Injury;interest;Intrinsic drive;Kinetics;Label;Liver;loss of function;Maintenance;MAP Kinase Gene;Memory;Molecular;Mus;Myofibroblast;Nature;Organ;p38 Mitogen Activated Protein Kinase;Pathologic;Pattern;periostin;pharmacologic;Phenotype;Phenylephrine;preservation;prevent;Process;Profibrotic signal;Recovery;Regulation;Reporter;response;Role;Signal Transduction;single-cell RNA sequencing;Skin;Stimulus;Stress;Tamoxifen;targeted treatment;Therapeutic;Therapeutic Intervention;Tissues;Ventricular Remodeling;Work;wound healing

PROJECT_TITLE: Regulators of Myofibroblast State Stability & Fibrotic Responsiveness of the Heart

STUDY_SECTION: MPPA

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


ED_INST_TYPE: OTHER SPECIALIZED SCHOOLS

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE The Gerontology Enriching MSTEM (GEMSTEM) to Enhance Diversity in Aging program integrates research, education, and professionalization for aging curious undergraduate scholars at the University of Southern California from underrepresented minority backgrounds. The primary objective of GEMSTEM is to advance diversity in aging research and health disparities research in aging by providing early access to research, providing individual mentorship opportunities, personalized academic and career advice, and establishing an enriched community of peer scholars to pipeline into future careers in gerontology.

PI_NAMEs: AILSHIRE, JENNIFER A;CURRAN, SEAN P (contact);WALSH, JOHN P

PROGRAM_OFFICER_NAME: CARTER, CHRISTY

PROJECT_TERMS: Aging;aging population;Area;Biological Process;Biology;California;career;career development;cognitive neuroscience;college;Communities;Complex;Creativeness;Curiosities;Degree program;design;Disabled Persons;Disparity;economic disparity;Education;education research;equity, diversity, and inclusion;ethnic minority;experience;Faculty;Fostering;Future;Gerontology;Geroscience;Goals;graduate school;Health Disparities Research;health disparity;health disparity populations;Home;Individual;Inequity;Infrastructure;innovation;interest;Leadership;Los Angeles;medical schools;meetings;Mentors;Mentorship;Mission;Modeling;Native-Born;next generation;older adult;Older Population;Participant;peer;Policies;Population;population health;Population Heterogeneity;Program Sustainability;programs;racial minority;recruit;Reduce health disparities;Research;Research Personnel;Research Training;Resources;Role;Rural;school district;Schools;science, technology, engineering, mathematics, and medicine;Sexual and Gender Minorities;skills;social;social engagement;Social Processes;Social support;Socialization;socioeconomics;Sociology;STEM career;STEM field;Structure;student participation;Students;success;Talents;Training Activity;Training and Education;training opportunity;undergraduate research experience;undergraduate student;Underrepresented Minority;underrepresented minority student;Underrepresented Populations;Universities;University resources;Woman


NIH_SPENDING_CATS: Biotechnology;Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Liver Cancer;Liver Disease;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: DALLAS

ORG_DEPT: PEDIATRICS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: NARRATIVE Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related death in the United States and innovative strategies for detection, prevention, and treatment will depend heavily on mouse models. The current HCC models are inadequate because they do not take into account the biology of their cells of origin, a problem which we will address using lineage tracing and genetic manipulation experiments in a large panel of CreER mice we developed to label a broad range of specific hepatocyte subpopulations. Success in this project will provide the community with a large panel of important tools and allow the field to focus on important subpopulations that contribute to HCC biology.

PI_NAMEs: ZHU, HAO  (contact)

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: Address;Architecture;Biological;Biological Assay;Biology;Cancer Etiology;carcinogenesis;Cause of Death;cell type;Cells;Cessation of life;Chemicals;Chronic;chronic liver injury;Cirrhosis;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Communities;Competence;Death Rate;Detection;Development;Etiology;Event;experimental study;Frequencies;Gene Expression;Genes;genetic manipulation;genome editing;Hepatic;Hepatic lobule;Hepatocyte;Heterogeneity;Homeostasis;Hypoxia;improved;Incidence;Injury;innovation;insight;Knock-in;Label;Liver;liver cancer model;liver injury;Liver Stem Cell;Maintenance;Malignant - descriptor;Malignant Epithelial Cell;Malignant Neoplasms;Metabolic;Metabolic Diseases;Metabolism;Methods;Modeling;Molecular;mouse model;Mouse Strains;Mus;Mutate;neoplastic;nonalcoholic steatohepatitis;novel;Nutritional;Outcome;Overnutrition;Pathway interactions;Patients;Ploidies;Population;Predisposition;Prevention;Primary carcinoma of the liver cells;progenitor;Reagent;regenerative;Regenerative capacity;regenerative cell;Source;stem cell population;success;Therapeutic;tool;tumor;Tumor Biology;tumor initiation;United States

PROJECT_TITLE: Improving hepatocellular carcinoma mouse modeling by understanding the malignant potential and biology of liver cell subpopulations

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-N(55)R]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cancer;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);HIV/AIDS;Heart Disease;Lung;Lung Cancer;Prevention;Sleep Research;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Smoking is a leading public health problem, especially for adults living with HIV (ALHIV), who have higher rates of smoking and more cardiovascular disease than the general population. Poor sleep is more prevalent among ALHIV, more prevalent among smokers, can be caused by smoking cessation attempts, predicts relapse to former smoking patterns, and is linked to multiple comorbidities including cardiovascular disease. This study will prospectively test a novel sleep health intervention in ALHIV smokers to determine if it improves sleep health and enhances quit rates, and whether improvements in cognition and affect mediate the relationship between sleep health and smoking cessation.

PI_NAMEs: FANTRY, LORI E (contact);GRANDNER, MICHAEL A;PATTERSON, FREDA

PROGRAM_OFFICER_NAME: HERRMANN, EVAN SULLIVAN

PROJECT_TERMS: Acute;addiction;Address;Adult;Affect;Affective;arm;Beds;Behavior;Biochemical;Biological Markers;biomarker identification;Blood Pressure;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular risk factor;cigarette smoke;cigarette smoking;Cognition;Cognitive;Cognitive Therapy;comorbidity;Counseling;Data;Development;efficacy evaluation;Electronic cigarette;Elements;Exhibits;experience;Failure;Fibrin fragment D;follow-up;Future;General Population;Goals;Health;Health behavior change;Health education;Health Promotion;HIV;HIV Infections;HIV Seropositivity;Hour;improved;improvement on sleep;insight;Intercellular adhesion molecule 1;interest;Interleukin-6;Intervention;Link;Lipids;Measures;Mediating;modifiable risk;Morbidity - disease rate;mortality;multidisciplinary;National Institute of Drug Abuse;Nicotine Dependence;nicotine replacement;nicotine use;non-smoker;Nonpharmacologic Therapy;novel;Participant;Pathway interactions;Pattern;Pilot Projects;pilot test;poor sleep;Population;Prediction of Response to Therapy;Prevalence;Prevention approach;programs;prospective test;Public Health;Randomized;Randomized Controlled Clinical Trials;recruit;Relapse;relapse prediction;Reporting;Research;Research Priority;Risk;Risk Factors;Role;Sleep;sleep behavior;sleep difficulty;sleep health;Sleeplessness;Smoker;Smoking;smoking addiction;smoking cessation;Smoking Cessation Intervention;smoking intervention;smoking prevalence;social;standard care;Strategic Planning;success;Symptoms;Testing;theories;therapy development;Time;TNF gene;tobacco cessation intervention;Tobacco Use Cessation;Training;treatment optimization;treatment response;United States National Institutes of Health;varenicline;Vascular Cell Adhesion Molecule-1;Work

PROJECT_TITLE: Using Sleep Health to Optimize Smoking Cessation Treatment Response in HIV-Positive Adults

STUDY_SECTION: HCCS

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


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Machine Learning and Artificial Intelligence;Neurosciences

ORG_CITY: Boulder

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: PROJECT NARRATIVE Fluorescence lifetime imaging microscopy (FLIM) is a type of fluorescence imaging technologies that is gaining popularity in biomedicine because it delivers the most direct insight into the molecular conformation and the biological environment of a fluorophore. This project will address the key imaging speed challenge that limits FLIM’s widespread application by reducing the instrument response function and increasing the maximum photon counting rate. In addition, two-photon excitation will be utilized to reduce the phototoxicity and machine learning framework will be developed to accelerate the FLIM data analysis.

PI_NAMEs: HUANG, SHU-WEI  (contact)

PROGRAM_OFFICER_NAME: ANDERSON, AFROUZ AZARI

PROJECT_TERMS: Acceleration;Address;Age related macular degeneration;Alzheimer's Disease;Benchmarking;Biological;brain tissue;Color;Complex;cryogenics;Data Analyses;Detection;Development;Diagnosis;Dietary Carotenoid;Dyes;Early Diagnosis;Electrons;Environment;ex vivo imaging;experimental study;Family suidae;Feedback;Fiber;Fluorescence;fluorescence imaging;fluorescence lifetime imaging;fluorescence microscope;fluorophore;Fundus;Future;Hydration status;Image;imaging study;Imaging technology;in vivo;innovation;insight;instrument;invention;Ions;Lasers;Light;light microscopy;light weight;Lutein;Machine Learning;machine learning framework;macula;Measures;Metabolism;Methods;microscopic imaging;Molecular Conformation;Monitor;multiphoton microscopy;Mus;nanowire;Neurodegenerative Disorders;Neurosciences;Nicotinamide adenine dinucleotide;Noise;Ophthalmology;Optics;Phase;photon-counting detector;Photons;Phototoxicity;Physiologic pulse;protein protein interaction;Protocols documentation;response;Retina;Silicones;Source;Speed;statistics;System;Technology;Temperature;three dimensional structure;Time;Tissue Model;Tissues;Training;two-dimensional;two-photon;Viscosity;zeaxanthin

PROJECT_TITLE: Two-photon fluorescence lifetime imaging microscopy utilizing the space-time duality

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-P(81)S]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: SAINT LOUIS

ORG_DEPT: GENETICS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative: Teams with diverse perspectives outperform those with more limited perspective. Programs that promote a diverse scientific workforce are the essential to continue the tradition of scientific excellence in the United States. This proposal seeks funding for an undergraduate research program that enables students from underrepresented backgrounds to carry out research and participate in academic and professional development events during their junior and senior years. These activities will prepare students to gain entry into and excel in PhD and MD/PhD programs nationwide, empowering the United States to remain the world-wide leaders in scientific research.

PI_NAMEs: SKEATH, JAMES BENJAMIN (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: Automobile Driving;CCL7 gene;college;Communities;Critical Thinking;Critiques;Doctor of Philosophy;Education;experience;Face;Feedback;Financial Support;Funding;Goals;Individual;innovation;matriculation;Mission;next generation;notch protein;Population Heterogeneity;programs;Request for Applications;Research;Science;Scientist;Source;Student recruitment;Students;success;summer research;Time;Training;Underrepresented Students;underserved community;United States;Universities;Washington;Writing

PROJECT_TITLE: MARC U-STAR PROGRAM AT WASHINGTON UNIVERSITY IN ST. LOUIS

STUDY_SECTION: TWD

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


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Clinical Research;Comparative Effectiveness Research;Lung;Palliative Care;Rare Diseases

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Healthcare provided in intensive care units often fails to meet the needs of patients who are near the end of life, their families, and their clinicians. This study will investigate a new model of care for patients with respiratory failure called a time-limited trial, which includes a trial of life support, clear milestones, and a timeline to help evaluate whether the patient is recovering. The knowledge generated in this proposal will be used to ensure medical decisions for patients with respiratory failure reflect their individual goals, values, and priorities, and can be extended to patient populations with other serious illnesses in the future.

PI_NAMEs: KRUSER, JACQUELINE MARIE (contact)

PROGRAM_OFFICER_NAME: ZHOU, GUOFEI

PROJECT_TERMS: Acute respiratory failure;Address;Adherence;Agreement;care delivery;Caring;Cessation of life;clinical practice;Clinical Trials;cohort;Cohort Studies;Communication;Complex;Conflict (Psychology);cost;Critical Care;Data;design;Development;Distress;end of life;end of life care;end of life outcomes;Engineering;Ensure;Environment;Ethnography;experience;Family;Foundations;Future;Goals;Health;Healthcare;Hospitals;improved;Individual;Intensive Care Units;interest;Intervention;Interview;Knowledge;Length of Stay;Life;Life Experience;Literature;Maps;Measures;Mechanical ventilation;Medical;member;Methods;Modeling;Morals;National Heart, Lung, and Blood Institute;Nested Case-Control Study;observational cohort study;Observational Study;Outcome;Palliative Care;Patient Care;patient population;Patient-Focused Outcomes;Patients;Pattern;prevent;Process;process improvement;Process Measure;Professional Organizations;prognostic;prospective;psychological distress;Quality of Care;Randomized, Controlled Trials;Recovery;Research;Respiratory Failure;Role;Structure;surrogate decision maker;System;Testing;Time;timeline;tool;Uncertainty;Variant;Visual;visual map;Work

PROJECT_TITLE: Optimizing Time-Limited Trials of Mechanical Ventilation in Acute Respiratory Failure: A Mixed Methods Observational Study

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


ORG_NAME: DANA-FARBER CANCER INST

PHR: Narrative Nearly half of human cancers overexpress long interspersed element-1 (LINE-1) transposable element. We have found that this expression creates unique molecular requirements for cell growth. Here, we will test the hypothesis that these pathways are required to eliminate LINE-1 retrotransposition intermediates and prevent collisions between these intermediates and DNA replication forks.

PI_NAMEs: BURNS, KATHLEEN H (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Affect;BARD1 gene;Binding;Biochemical;biological adaptation to stress;Biological Assay;BRCA1 gene;cancer cell;Cancer Cell Growth;cancer genome;cell growth;Cell Nucleus;Cell Physiology;Cell Survival;Cells;Code;Complement;Complex;Conflict (Psychology);coping;CRISPR/Cas technology;Cytostatics;cytotoxic;Data;Detection;DNA;DNA biosynthesis;DNA fiber assay;DNA Repair;DNA Repair Gene;DNA Repair Pathway;DNA replication fork;DNA Transposable Elements;endonuclease;experimental study;Fanconi Anemia-BRCA Pathway;Fanconi's Anemia;fitness;Foundations;Funding Opportunities;Gene Mutation;Genes;Genome;genome-wide;Genomics;Human;Immunofluorescence Immunologic;in vivo;Inhibition of Cancer Cell Growth;International;Knock-out;Length;Lethal Genes;Ligation;Long Interspersed Elements;Malignant Neoplasms;Maps;Mediating;Mediator;Methods;Methylation;Mobile Genetic Elements;Molecular;mutant;Mutate;Mutation;next generation sequencing;Normal Cell;Nuclear;Open Reading Frames;overexpression;Pathway interactions;Poly(ADP-ribose) Polymerase Inhibitor;Poly(ADP-ribose) Polymerases;prevent;Process;promoter;Proteins;replication stress;Research;restraint;Retrotransposition;Retrotransposon;Reverse Transcription;RNA-Binding Proteins;RNA-Directed DNA Polymerase;Role;S phase;Series;Short Interspersed Nucleotide Elements;Signal Pathway;Signal Transduction;Site;synthetic lethal interaction;System;Testing;The Cancer Genome Atlas;Therapeutic;translocase;Tumor Suppressor Genes;ubiquitin ligase;Visualization

PROJECT_TITLE: Characterizing the LINE-1 Retrotransposition-Replication Conflict

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


ORG_DEPT: UROLOGY

PHR: Over 90% of men with advanced prostate cancer (PCa) develop skeletal metastases which subsequently leads to their death. This Program is composed of a multidisciplinary team focused on understanding how the cancer spreads to and thrives in the skeleton so that we can develop methods to prevent or treat the spread of PCa to the bone.

PI_NAMEs: KELLER, EVAN T (contact)

PROJECT_TERMS: Abscisic Acid;Address;Adopted;advanced prostate cancer;Animal Model;Animals;anti-cancer research;Apoptotic;Biological Assay;Biology;Biometry;Blood;bone;bone cell;Bone Marrow;Bone Marrow Examination;Bone Tissue;cancer cell;Cells;Cessation of life;Chemoresistance;chemotherapy;Clinical Trials;Development;Ensure;Environment;Evaluation;experience;Experimental Animal Model;Family;Fostering;GDF15 gene;Grant;Growth;Health;Histology;Human;Hypoxia;Image;Immunosuppression;Incidence;Injections;Invaded;Leadership;Macrophage;Malignant neoplasm of prostate;Malignant Neoplasms;Measurement;men;Metastatic Neoplasm to the Bone;Metastatic Prostate Cancer;Methods;Modeling;mouse model;multidisciplinary;Mus;neoplastic cell;new therapeutic target;novel;Nuclear;Osteocytes;Pain;Patient Care;Phenotype;Play;Polyploidy;Predisposition;prevent;programs;prostate cancer cell;prostate cancer metastasis;prostate cancer progression;Publications;receptor;Reporting;Research;Research Personnel;Resource Sharing;Role;Running;Sampling;Signal Transduction;Skeleton;Stress;Sum;therapeutic target;therapy resistant;tumor;tumor growth;Tumor Promotion;tumorigenesis

PROJECT_TITLE: The Biology of Prostate Cancer Skeletal Metastases


NIH_SPENDING_CATS: Cancer;Clinical Research;Prostate Cancer;Urologic Diseases

PHR: Skeletal metastases associated with advanced prostate cancer continue to kill more than 29,000 men per year in the United States. In this proposal, we identify polyploid giant cancer cells that exist as a subset of cells (1-2%) within a tumor population and act as central actuators of lethal disease by mediating therapeutic resistance and initiating metastasis.

PI_NAMEs: PIENTA, KENNETH J. (contact)

PROJECT_TERMS: advanced prostate cancer;androgen independent prostate cancer;Appearance;Autopsy;Biology;Biopsy;Blood;cancer cell;cancer stem cell;Cell Cycle;Cell fusion;Cell Survival;Cells;chemotherapy;Clinical;Cytokinesis;Data;deprivation;Development;Disease;Disease Management;Disseminated Malignant Neoplasm;Drug resistance;Event;Exhibits;G0 Phase;Genomics;Glucose;Human;human tissue;Hypoxia;In Vitro;in vivo Model;Individual;Invaded;Literature;Malignant - descriptor;Malignant neoplasm of prostate;Measures;Mediating;men;Mesenchymal;Metastatic Neoplasm to the Bone;migration;Modeling;Morphologic artifacts;Morphology;Motility;mouse model;Mus;Neoplasm Circulating Cells;Neoplasm Metastasis;neoplastic cell;novel;Patients;Pharmaceutical Preparations;Phenotype;Polyploidy;Population;pressure;Prevalence;prognostic significance;Proliferating;Property;Reporter;Reporting;Research;Resistance;Resistance development;Role;senescence;Source;stem;Stress;stressor;taxane;Therapeutic;Therapeutic Intervention;therapy resistant;Time;tissue culture;Tissue Sample;tissue/cell culture;Tissues;tumor;tumor progression;Tumor Tissue;tumorigenesis;United States;Work

PROJECT_TITLE: Project 1: Polyploid giant cancer cells are central actuators of tumorigenesis, skeletal metastasis, and therapeutic resistance


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Immunotherapy;Liver Cancer;Liver Disease;Orphan Drug;Rare Diseases

ORG_NAME: EMORY UNIVERSITY

PHR: Project Narrative Hepatocellular carcinoma is third most common cause of cancer-related death worldwide. Recurrence after curative surgery is influenced by interactions with white blood cells in the immune system. The proposed research will explore the impact of a novel immune-based systemic therapy given before surgery. We will obtain patient tissue and blood to define the mechanism of this novel treatment combination, and identify factors associated with response or resistance that can be used in future studies.

PI_NAMEs: AKCE, MEHMET ;LESINSKI, GREGORY B. (contact)

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Adjuvant;Adjuvant Therapy;anti-cancer research;anti-PD-L1;anti-PD-L1 antibodies;anti-PD1 antibodies;Antibody Therapy;Attention;Biological Assay;Biopsy;Biopsy Specimen;Blood;Blood specimen;Blood Vessels;BRAF gene;Cancer Etiology;Cancer Patient;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Maintenance;Cells;Cessation of life;chemokine;chemotherapy;Clinical;Clinical Data;Clinical Management;Clinical Trials;combinatorial;Combined Modality Therapy;Communities;cost;CSF1R gene;Curative Surgery;CXCL10 gene;CXCR3 gene;cytokine;Cytometry;Data;design;digital;Disease;Disease Progression;disorder control;Environment;Enzyme-Linked Immunosorbent Assay;Excision;exhaust;Fibroblast Growth Factor Receptor 1;Fibroblasts;Fostering;Funding;Future;high risk;Human;Immune;immune checkpoint blockade;Immune system;Immune Targeting;Immunofluorescence Immunologic;Immunotherapy;improved;Infiltration;Infrastructure;inhibitor;innovation;Institution;interdisciplinary approach;interest;Invaded;KDR gene;Keratin-19;Knowledge;Leukocytes;liver cancer model;Lymphocyte;Macrophage Colony-Stimulating Factor;Malignant Epithelial Cell;malignant stomach neoplasm;Mediating;Mediator;Memory;mouse model;multidisciplinary;Myeloid Cells;Myeloid-derived suppressor cells;Neoadjuvant Therapy;neoplastic cell;next generation;novel;Oncogenic;Oncology;Operative Surgical Procedures;Oral;Outcome;Pathway interactions;patient subsets;Patients;PD-1/PD-L1;PD-L1 blockade;PDGFRB gene;pembrolizumab;Perioperative;Pharmaceutical Preparations;phase II trial;Phenotype;Phosphotransferases;Physicians;Platelet-Derived Growth Factor;pre-clinical;preclinical study;Prevention;Primary carcinoma of the liver cells;Production;Prognosis;programs;Proteins;Proto-Oncogene Protein c-kit;receptor;Recurrence;Regimen;Regulatory T-Lymphocyte;Reporting;Research;Resected;Resistance;resistance mechanism;response;Risk;sample collection;Signal Pathway;Specimen;STAT protein;stem;synergism;synthetic polymer Bioplex;Systemic Therapy;T cell infiltration;T cell receptor repertoire sequencing;T-Lymphocyte;T-Lymphocyte Subsets;targeted treatment;TEK gene;Testing;Therapeutic Studies;TIE-2 Receptor;Tissue Sample;Tissues;Transcript;Translating;translational approach;Transplantation Surgery;tumor;Tumor Antigens;tumor microenvironment;Tumor-associated macrophages;Vascular Endothelial Growth Factors

PROJECT_TITLE: Preoperative immunotherapy in Hepatocellular Carcinoma


NIH_SPENDING_CATS: Cancer;Clinical Research;Prostate Cancer;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Urologic Diseases

PHR: Project Narrative DTCs may lie dormant for years prior to becoming activated to generate a lethal metastatic disease. This project aims to understand the molecular mechanisms which regulate dormancy. This knowledge will be used to develop a rationale for therapeutic targets focused on dormancy signaling to either prevent relapse or specifically activate tumor growth in an adjuvant setting so that conventional chemotherapeutic agents targeting proliferating cells may be used as adjuvant therapy to eradicate DTCs in marrow.

PI_NAMEs: TAICHMAN, RUSSELL S (contact)

PROJECT_TERMS: Abscisic Acid;Adjuvant;Adjuvant Therapy;Aftercare;Agonist;antagonist;Binding;biological adaptation to stress;Biology;BMP4;bone;Bone Marrow;Bone Marrow Aspiration;Cancer Patient;cancer stem cell;cancer survival;Cell Count;Cell Cycle;Cell Cycle Arrest;cell growth;Cell Proliferation;Cell Separation;cell type;Cells;chemotherapeutic agent;chemotherapy;Coculture Techniques;Data;Disease;effective therapy;Genetic Transcription;Growth;hematopoietic stem cell niche;Human;human disease;human model;Immune;improved;in vivo;knock-down;Knowledge;Link;Maintenance;Malignant neoplasm of prostate;Mammalian Cell;Mammals;Marrow;Mediator;Mesenchymal Stem Cells;Metastatic Neoplasm to the Bone;Metastatic Neoplasm to the Bone Marrow;Modeling;Molecular;Neoplasm Metastasis;neoplastic cell;Pathway interactions;Plant Growth Regulators;Plants;Play;Proliferating;prostate cancer cell;prostate cancer cell line;prostate cancer metastasis;receptor;Receptor Signaling;Recurrence;relapse prevention;Resistance;response;Role;Signal Induction;Signal Transduction;Soil;stemness;System;targeted treatment;Testing;Therapeutic;therapeutic target;Treatment outcome;tumor;tumor growth

PROJECT_TITLE: Project 2: Abscisic Acid Regulates Dormancy of Disseminated Tumor Cells in Bone Marrow


PHR: Project Narrative Prostate cancer (PCa) is the most common cancer of American men and the second leading cause of cancer- related death most often due to bone metastasis. This project will explore how the cancer changes the bone environment so that it becomes conducive to bone metastasis. This will help identify targets to prevent or treat bone metastasis.

PROJECT_TERMS: Address;advanced prostate cancer;American;Androgen Antagonists;Apoptosis;Apoptotic;Autophagocytosis;Biology;bone;bone cell;Bone Resorption;cancer cell;Cancer Etiology;Cancer Patient;cancer seeding;Cell fusion;cell growth;Cell Physiology;Cells;Cessation of life;Chemicals;Chemoresistance;Clinical;Collaborations;Data;DNA Damage;Drug Efflux;Drug resistance;efflux pump;Environment;enzalutamide;Family;Feedback;GDF15 gene;Genetic;Growth;improved;In Vitro;in vivo;Ingestion;Invaded;knock-down;Knowledge;Malignant neoplasm of prostate;Malignant Neoplasms;Measures;mechanotransduction;Mediating;Mediator;men;Metastatic Neoplasm to the Bone;mouse model;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel;Osteoblasts;osteoclastogenesis;Osteoclasts;Osteocytes;Osteolytic;Pathway interactions;Patient Care;PDGFRA gene;Phenotype;Polyploidy;pressure;prevent;Production;Proliferating;prostate cancer cell;prostate cancer metastasis;prostate cancer progression;Proteins;receptor;Resistance;response;Role;Signal Transduction;Site;soft tissue;Stromal Cell-Derived Factor 1;taxane;Testing;therapeutic target;Time;Tissue Microarray;tumor;Writing

PROJECT_TITLE: Project 3: The osteocyte-driven GDF15:GFRAL axis promotes prostate cancer bone metastasis


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: HADLEY

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

PHR: Project Narrative Many human diseases are characterized by the untimely degradation of proteins by the 26S proteasome. Insights into the molecular mechanisms by which cells regulate the 26S proteasome can be used to devise new therapies. This research will aid efforts to develop drugs to treat cancers relying on the proteasome for survival.

PI_NAMEs: STRIETER, ERIC ROBERT (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: 26S proteasome;Antibodies;ATP-Dependent Proteases;Biochemical Pathway;Biochemistry;Catalytic Domain;Cell Cycle;Cells;design;Deubiquitination;Development;DNA Damage;Embryo;Foundations;Goals;Histones;Human;human disease;In Vitro;insight;Malignant Neoplasms;Molecular;multicatalytic endopeptidase complex;Mus;nanobodies;Nervous System Disorder;new therapeutic target;novel therapeutics;overexpression;Oxidative Stress;Pharmaceutical Preparations;Prognosis;programs;protein degradation;Protein Engineering;Proteins;Proteome;receptor binding;recruit;Research;response;Role;targeted treatment;tool;Tumor Suppressor Proteins;Ubiquitin;ubiquitin isopeptidase;X-Ray Crystallography

PROJECT_TITLE: Defining the Function of Proteasomal Deubiquitinases


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Prostate Cancer;Urologic Diseases

PHR: Project Narrative It is proposed that cells in the bone marrow known as ‘tumor associated macrophages’ engulf dead and dying cancer cells and in return produce factors that further support tumor growth. This project will identify the critical steps in this process, determine the impact of a specific cell surface signal in the support of tumor growth in the bone marrow, and identify targetable strategies to inhibit the process and provide resolution. Using novel experimental models, these studies will provide new insights into skeletal metastasis, and propose a potential therapy for reducing the devastating consequence of tumor metastasis in bone.

PI_NAMEs: MCCAULEY, LAURIE K. (contact)

PROJECT_TERMS: Abscisic Acid;Acceleration;Affect;Anti-Inflammatory Agents;Antibodies;Apoptotic;Biochemical;Bioinformatics;Biological Response Modifiers;Biology;bone;Bone Marrow;Bone Marrow Neoplasms;cancer cell;Cancer Patient;cancer therapy;carcinogenesis;CD14 gene;Cd68;Cell Death;cell growth;Cell Lineage;Cell surface;Cells;Characteristics;Collaborations;CXCL5 gene;Data;design;Disease;Disseminated Malignant Neoplasm;Experimental Models;Funding;Gatekeeping;Gene Expression Profile;Gene Targeting;Genetic Transcription;Grant;Growth;Homeostasis;Human;Immune response;Immunoglobulins;immunoregulation;Immunosuppression;In Vitro;in vivo;Incidence;Inflammatory;insight;Laboratories;Macrophage;Malignant neoplasm of prostate;Malignant Neoplasms;Marrow;Mediating;Mediator;Metastatic Neoplasm to the Bone;Metastatic Prostate Cancer;Modeling;monocyte;mouse model;Mucins;Myelogenous;Neoplasm Metastasis;neoplastic cell;neutralizing antibody;Normal Cell;novel;Osteocytes;Patients;peripheral blood;Phagocytes;pharmacologic;Phenotype;phosphatidylserine receptor;Phosphatidylserines;Play;Polyploidy;Process;prognostic;programs;prostate cancer cell;prostate cancer metastasis;Prostate Cancer therapy;Relapse;Resolution;response;Role;Serine;Signal Pathway;Signal Transduction;single cell sequencing;single-cell RNA sequencing;skeletal;Supporting Cell;T-Cell Receptor;T-Lymphocyte;targeted cancer therapy;Therapeutic;tumor;Tumor Burden;tumor growth;tumor microenvironment;tumor progression;Tumor-associated macrophages

PROJECT_TITLE: Project 4: The role of bone marrow macrophages in skeletal metastasis


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Cancer;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Immunotherapy;Rare Diseases

ORG_CITY: STANFORD

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: This research program will address mechanisms by which the immune system interfaces with oral cancer and how tumors can influence the immune response. The information gained from these studies will provide insight into ways to improve immunotherapy and predict responses.

PI_NAMEs: SUNWOO, JOHN B (contact)

PROGRAM_OFFICER_NAME: CHEN, ZHONG

PROJECT_TERMS: advanced disease;Area;Cell Physiology;Cells;Epithelium;Face;Human;Immune;immune checkpoint blockade;Immune response;Immune system;Immune Targeting;immunoregulation;Immunotherapy;improved;insight;interest;Investigation;malignant mouth neoplasm;Malignant Neoplasms;Mediating;Minority;mouse model;mouth squamous cell carcinoma;mucosal site;Natural Killer Cells;neoantigens;neoplastic cell;novel;Operative Surgical Procedures;Oral;Oral mucous membrane structure;predicting response;pressure;Primary Neoplasm;programmed cell death protein 1;programs;Radiation;Research;response;Sampling;Sublingual Region;Survival Rate;Tongue;tumor;tumor heterogeneity;tumor microenvironment

PROJECT_TITLE: Reprogramming the Tumor-Immune Interface in Oral Cancer


PROJECT_TERMS: Animal Welfare;Animals;Area;Biology;Biometry;Collaborations;Communication;Communities;Computers;Databases;Dedications;DNA;Ensure;experience;experimental analysis;Experimental Designs;experimental study;Extramural Activities;Funding;Goals;Human Resources;human subject;Laboratory Personnel;Leadership;Malignant neoplasm of prostate;Manuscripts;meetings;member;Metastatic Neoplasm to the Bone;Michigan;Productivity;programs;Radiation;Reporting;repository;Research;Research Personnel;Resource Sharing;Resources;Role;Science;Scientist;Series;Services;United States National Institutes of Health;Universities;Visit

PROJECT_TITLE: Core A - Administrative Core


NIH_SPENDING_CATS: Aging;Biomedical Imaging;Cancer;Prostate Cancer;Urologic Diseases

PHR: Project Narrative Bone metastases are a serious and frequent clinical complication of prostate cancer. This core will provide animal models to help identify mechanisms and targets to attack this important aspect of prostate cancer.

PROJECT_TERMS: American;Anesthesia procedures;animal data;Animal Experiments;animal imaging;Animal Model;Animals;Biology;bioluminescence imaging;Board Certification;bone;Bone Density;cancer imaging;Clinical;Collaborations;college;Complication;Data Analyses;Dual-Energy X-Ray Absorptiometry;Ensure;experience;experimental study;Genetically Engineered Mouse;Goals;Grant;Human Resources;Image;Implant;implantation;in vivo;in vivo imaging;Individual;Injections;Internal Medicine;Laboratory Animal Medicine;Laboratory Animals;Maintenance;Malignant neoplasm of prostate;Metastatic Neoplasm to the Bone;Methods;Modeling;Nature;neoplastic cell;Oncologist;Performance;Procedures;programs;Research;Research Personnel;Resource Sharing;Role;Scanning;Services;soft tissue;spine bone structure;Standardization;Translating;tumor;vertebra body;Veterinarians

PROJECT_TITLE: Core B - Animal Core


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Human

PHR: Public Health Relevance Neurodevelopmental disorders (NDDs) are heterogeneous genetic diseases with defects in neuron function, but molecular mechanisms underlying these pathologies remain poorly understood. The goal of this study is to elucidate the mechanism by which high-confidence NDD risk gene ZNF462 promotes epigenetic silencing of non-neural genes to ensure neural cell identity. Our studies will provide important insights into the precise regulation of facultative heterochromatin-mediated gene repression, and will identify strategic paths toward novel therapies for NDDs.

PI_NAMEs: BELL, OLIVER  (contact)

PROGRAM_OFFICER_NAME: LEINWAND, SARAH GOLDBERG

PROJECT_TERMS: 3-Dimensional;Affect;Architecture;autism spectrum disorder;Automobile Driving;Binding;Binding Sites;Biochemical;Biological;Biological Assay;C2H2 Zinc Finger;CCCTC-binding factor;Cell Differentiation process;Cells;Central Nervous System;Child;Chromatin;chromatin modification;Chromosomes;Complement;Complex;Coupled;CRISPR screen;de novo mutation;Defect;Development;Developmental Delay Disorders;Developmental Gene;Disease;DNA Binding;DNA Binding Domain;DNA Transposable Elements;Endoderm;Endoderm Cell;Enhancers;Ensure;Epigenetic Process;epigenetic silencing;epigenomic profiling;Epithelium;Essential Genes;Etiology;euchromatic histone methyltransferase 1;Evolution;exome sequencing;experimental study;Failure;GATA4 gene;Gene Expression;Gene Expression Profile;Gene Expression Regulation;gene regulatory network;gene repression;Gene Silencing;Genes;Genetic;genetic corepressor;Genetic Diseases;Genetic Enhancer Element;Genetic Predisposition to Disease;Genetic Transcription;Genome;genome sequencing;genomic profiling;Genomics;Goals;Heritability;Heterochromatin;heterochromatin-specific nonhistone chromosomal protein HP-1;Heterozygote;histone modification;Homodimerization;Human;human embryonic stem cell;Impairment;insight;Knockout Mice;Link;loss of function mutation;Loss of Heterozygosity;Maintenance;Mediating;Methods;Missense Mutation;Molecular;Molecular Conformation;Monitor;Mouse Embryonic Stem Cells;Mus;Mutation;nerve stem cell;neural;Neurobiology;neurodevelopment;Neurodevelopmental Disorder;Neuroepithelial;neurogenesis;Neurons;neuropathology;neuropsychiatry;novel;novel strategies;novel therapeutics;Orthologous Gene;Pathology;Phenotype;Play;prevent;Protein Isoforms;Proteins;public health relevance;recruit;Regulation;Reporter;Reporter Genes;Repression;Research;risk variant;Role;SOX17 gene;Specificity;stem cell differentiation;stem cells;Structure;Syndrome;Tertiary Protein Structure;Testing;Traction;transcription factor;transcriptomic profiling;Variant;whole genome;Work

PROJECT_TITLE: Epigenetic Maintenance of Neural Cell Identity

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


NIH_SPENDING_CATS: Aging;Cancer;Clinical Research;Prostate Cancer;Urologic Diseases

PHR: Project Narrative The Bone Core of the Program Project will provide shared facilities and services for processing and interpretation of tissues from the animal models utilized in all projects of the program. The overall goal of the core facility is to provide centralized histologic and image analysis support for investigators in the project. Such a standardized format with provide valuable information and consistency across the projects in the program.

PI_NAMEs: DAI, JINLU  (contact)

PROJECT_TERMS: Anatomy;Animal Model;animal tissue;Biological Models;Biology;Blood;Board Certification;bone;Bone Marrow;Cell Separation;Clinical;Consultations;Core Facility;Decalcification;Experimental Designs;Goals;Histologic;histological specimens;Histology;Histopathology;Image Analysis;Immunohistochemistry;Laboratories;Malignant neoplasm of prostate;Measurement;Metastatic Neoplasm to the Bone;Methods;mineralization;Neoplasm Circulating Cells;neoplastic cell;Osteoclasts;Paraffin Embedding;Pathologic;Pathologist;Pathology;Patients;Physicians;Plastic Embedding;Process;Productivity;programs;Research Personnel;Resource Sharing;Resources;sample fixation;Sampling;Scientist;Serum;Services;skills;soft tissue;Specimen;Stains;Standardization;tissue processing;Tissue Sample;Tissues;Tumor Tissue;Urologic Oncology;Urologist

PROJECT_TITLE: Core C - Bone Core


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

ORG_CITY: LA JOLLA

ORG_NAME: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE

PHR: PROJECT NARRATIVE The most frequently mutated gene in cancer is TP53; however, it has been difficult to directly target this gene with drugs. We have discovered that a distinct family of phosphoinositide kinases encoded by the genes PIP4K2A and PIP4K2B create a synthetic lethality when deleted in the context of TP53 mutant tissues in mice or in human breast cancer cell lines. This work will define how this liability can be exploited in order to identify opportunities for therapeutic intervention for patients with TP53 mutations, especially in triple negative breast cancer where targeted therapies have not been effective.

PI_NAMEs: EMERLING, BROOKE M (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: 1-Phosphatidylinositol 4-Kinase;Alleles;anti-cancer;Autophagocytosis;Autophagosome;Biochemical;Biological;Biological Assay;Biological Models;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Model;Breast Cancer Patient;breast tumorigenesis;Cancer Cell Growth;cell growth;Cell model;Cell Survival;Cells;Cessation of life;chemotherapy;coping;Dependence;Disease;Embryo;Enzymes;Event;experience;Family;Fibroblasts;gain of function;Generations;Genes;Genetic;Genetic Engineering;Genetically Engineered Mouse;Germ Lines;glucose metabolism;Goals;Growth;Homeostasis;Human;Impairment;In Vitro;in vivo;interest;Intervention;knock-down;Light;Lipids;Location;loss of function;Lysosomes;Malignant Breast Neoplasm;Malignant Neoplasms;Metabolic;Metabolic Pathway;Metabolic stress;Minor;Molecular;mortality;mouse model;Mus;mutant;Mutate;Mutation;mutational status;neoplastic cell;new therapeutic target;novel;Outcome;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacologic Substance;Phenotype;phosphatidylinositol 5-phosphate;Phosphatidylinositols;Phosphorylation;Phosphotransferases;preclinical study;Prognosis;protein expression;Protein Kinase;quantitative imaging;Reactive Oxygen Species;response;Role;Sampling;Scheme;sensor;Signal Pathway;Signal Transduction;small hairpin RNA;Specimen;Speed;targeted cancer therapy;targeted treatment;therapeutic effectiveness;therapeutic evaluation;Therapeutic Intervention;Time;Tissues;TP53 gene;triple-negative invasive breast carcinoma;tumor;tumor growth;Tumor Suppressor Genes;tumorigenic;Woman;Work;Xenograft Model

PROJECT_TITLE: Non-Canonical Phosphatidylinositol Kinases in Triple Negative Breast Cancer

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Prevention;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human;Stomach Cancer

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: NARRATIVE The proposed experiments will examine how precancerous lesions form. We hypothesize that this process is conserved across organs and species and that there are fundamental genetic and cellular mechanisms that we can identify underlying how these lesions develop. We will test: the Hippo pathway in relation to other key genes regulating precancerous lesions like: IFRD1, p53, CDH1.

PI_NAMEs: MILLS, JASON C (contact)

PROGRAM_OFFICER_NAME: YASSIN, RIHAB R

PROJECT_TERMS: 3-Dimensional;Adult;Alleles;Apoptosis;Architecture;Autophagocytosis;Bacteria;Bioinformatics;Bypass;cancer risk;Cause of Death;CDH1 gene;Cell Cycle;Cell Differentiation process;Cell Reprogramming;Cells;Characteristics;Chief Cell;Chronic;Collaborations;Conserved Sequence;constitutive expression;Cytoskeleton;Data;data repository;Dedications;design;Development;Dose;Doxycycline;Embryo;Embryonic Induction;embryonic stem cell;Event;experimental study;FRAP1 gene;Gastric Metaplasia;gastric organoids;gastric tumorigenesis;Genes;Genetic;Goals;Helicobacter pylori;Human;Hydroxychloroquine;Image;imaging modality;Inflammation;inhibitor;Injury;Institution;Internal Ribosome Entry Site;LATS1 gene;Lesion;LoxP-flanked allele;Lysosomes;Malignant Neoplasms;malignant stomach neoplasm;Mediator;Metaplasia;Metaplastic Cell;Methylnitrosourea;Mitotic;Molecular;mouse model;mTOR Inhibitor;Mus;Mutagens;mutant;Mutant Strains Mice;Natural regeneration;Neurofibromin 2;new therapeutic target;Nuclear;Oncogenes;Organ;Organoids;paligenosis;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Phenotype;Phosphorylation;Phosphotransferases;Physiologic pulse;Population;premalignant;prevent;Process;progenitor;programs;Proliferation Marker;Property;Publishing;regenerative;Regenerative Medicine;Resolution;Risk;Risk Reduction;Role;scaffold;Signal Induction;Signal Transduction;Sirolimus;Smooth Pursuit;stem cell biomarkers;stem cell expansion;stem cells;Stomach;stomach body;Stomach Neoplasms;Stress;synergism;Tamoxifen;Technology;Testing;Time;tissue repair;TP53 gene;transcription factor;transcriptome sequencing;tumor;tumor progression;Tumor Promotion;tumorigenesis

PROJECT_TITLE: Mechanisms Governing Expansion of Embryonic Progenitor Cells (EPCs) inMetaplasia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-M(05)]


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

PHR: Triple negative breast cancer (TNBC) currently shows racial disparity between African American (AA) and Caucasian (CA) population. We discovered critical differences in the energy dependency of AA and CA TNBC. Using multiple OMICS and translational approaches, this project is aim to understand the difference in the energy dependency of AA TNBC compared to CA TNBC and its significance in the regulation of cancer pathways.

PI_NAMEs: KAIPPARETTU, BENNY ABRAHAM (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: Acetyl Coenzyme A;Address;African American;African American Women;Age;Animal Model;Arginine;argininosuccinate synthase;Aspartate;Benign;Bioinformatics;bioinformatics pipeline;Biology;Breast Cancer Cell;Breast Cancer cell line;breast cancer diagnosis;Breast Cancer Model;Breast Cancer Patient;c-myc Genes;cancer statistics;Caucasians;Cell model;Cells;Cessation of life;Characteristics;Citric Acid Cycle;Clinical;Clinical Data;Combined Modality Therapy;Dasatinib;Data;Dependence;Development;Diagnosis;Disease;Disparity;Drug resistance;Drug Targeting;druggable target;ethnic difference;Exhibits;experience;experimental study;Fatty Acids;Genomics;Glucose;high risk;In Vitro;in vivo;Incidence;inhibitor;Link;Longterm Follow-up;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Metabolic;metabolic abnormality assessment;Metabolic Activation;Metabolic Pathway;metabolomics;Mitochondria;Modeling;mortality risk;multiple omics;Neoplasm Metastasis;Nitric Oxide;Nuclear;Oncogenic;Outcome;oxidation;Pathway interactions;patient derived xenograft model;Patient-derived xenograft models of breast cancer;Patients;Polyamines;Population;Positioning Attribute;preclinical evaluation;preclinical study;prevent;Probability;Property;Proteomics;Publications;Publishing;Pyruvate;Pyruvate Carboxylase;Race;racial disparity;Regulation;Reporting;Research Personnel;Risk;Role;Sampling;Severities;Site;Socioeconomic Factors;Source;Specificity;SRC gene;stemness;targeted treatment;Therapeutic;Tissue Microarray;Tissues;translational approach;treatment response;triple-negative invasive breast carcinoma;tumor;tumor progression;Tumor Promotion;Tumor Tissue;tumorigenesis;urea cycle;Validation;White Women;Work

PROJECT_TITLE: RACIAL DISPARITY IN THE ENERGY DEPENDENCY OF TRIPLE NEGATIVE BREAST CANCER

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-B(55)R]


NIH_SPENDING_CATS: Antimicrobial Resistance;Bioengineering;Biotechnology;Emerging Infectious Diseases;Immunotherapy;Infectious Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: DAVIS

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE The central objective of our proposal is to design, build, and validate an integrated human “ImmuneChip” platform that mimics key dynamic features of the production and trafficking of white blood cells between the bone marrow, systemic circulation, and peripheral site of bacterial infection. The results of the project will create a technology that advances a new class of model systems to understand the innate immune response to infection.

PI_NAMEs: GEORGE, STEVEN CARL (contact)

PROGRAM_OFFICER_NAME: CHEN, JERMONT

PROJECT_TERMS: Address;Antibiotic Resistance;antibiotic resistant infections;Antibiotics;antimicrobial;Back;Bacteria;Bacterial Antibiotic Resistance;Bacterial Infections;bacterial resistance;Beds;Biological;Biological Models;Biology;Blood Vessels;Bone Marrow;Cells;Circulation;Collaborations;combat;Communication;Creativeness;design;design,build,test;Detection;Emergency Situation;Endothelium;experience;Extramedullary;Feedback;Fibroblasts;Goals;Gram-Positive Bacteria;Hematopoiesis;Hematopoietic Stem Cell Mobilization;Hematopoietic stem cells;Home;Homeostasis;Host Defense;Human;human model;Immune response;Immune system;Immunology;Immunotherapy;In Vitro;in vitro Model;Infection;Infectious Agent;Infectious Skin Diseases;innate immune mechanisms;Innate Immune Response;Innate Immune System;keratinocyte;Leukocytes;Link;Macrophage;Marrow;Mediator;Methicillin;Methicillin Resistance;Microfluidics;Modeling;Molecular;mouse model;Mus;Myelogenous;Nature;neutrophil;new technology;novel;novel therapeutics;organ on a chip;Osteomyelitis;pathogen;Pathogenicity;Patients;Pattern;Perfusion;Peripheral;Play;Process;Production;Proliferating;recruit;Research Personnel;residence;Resistance;response;Risk;Signal Transduction;Site;Skin;Skin wound healing;stem cell expansion;Sterility;Technology;Testing;three dimensional cell culture;three-dimensional modeling;Time;tissue culture;Tissues;trafficking;Virulence Factors;Virulent

PROJECT_TITLE: An Integrated In Vitro 3D Model of Human Bone Marrow and Peripheral Infection