ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Childhood Leukemia;Genetics;Hematology;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: Relevance Statement: Acute myeloid leukemia (AML) is the second most common childhood leukemia and has a dismal prognosis. For over 40 years AML chemotherapy has changed little with the continued reliance on ara-C, daunorubicin and etoposide as frontline agents. The proposed research seeks to prepare a sound scientific rationale to incorporate prognostic gene expression scores into the risk stratification of AML patients and revealing additional layers of the molecular basis of AML prognosis to guide the development of more effective treatments for AML.

PI_NAMEs: LAMBA, JATINDER K. (contact);POUNDS, STANLEY BARRETT

PROGRAM_OFFICER_NAME: AGRAWAL, LOKESH

PROJECT_TERMS: Acceleration;Achievement;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adult;Adult Acute Myeloblastic Leukemia;Ara-C;Azacitidine;Biological;Book Chapters;cancer genomics;Cell Line;chemotherapy;Childhood;Childhood Acute Myeloid Leukemia;Childhood Leukemia;Clinical;clinical practice;Clinical Trials;clinically significant;cohort;Collaborations;Combination Drug Therapy;CRISPR/Cas technology;Custom;Data;Daunorubicin;Decitabine;demethylation;Development;Diagnosis;Disease;Disease Resistance;DNMT3B gene;effective therapy;Enrollment;Environment;epigenomics;Etoposide;Evaluation;Exposure to;Failure;Florida;Foundations;Funding;Gene Expression;Genes;Genetic Transcription;genome wide association study;genome wide methylation;Genomics;In Vitro;innovation;International;Knock-out;Legal patent;leukemia treatment;Leukemic Cell;leukemic stem cell;Methods;Methylation;Molecular;molecular domain;novel;older patient;Outcome;Patients;Pediatric Oncology;Pediatric Oncology Group;pediatric patients;Pharmaceutical Preparations;Pharmacogenetics;Pharmacology;Procedures;Productivity;Prognosis;prognostic;Prognostic Factor;prospective;Publications;Qualifying;Randomized;Rare Diseases;Recurrent disease;Research;Research Personnel;Resistance;risk stratification;Saint Jude Children's Research Hospital;Sample Size;Sampling;Site;sound;Statistical Methods;success;symposium;transcriptomics;Translating;Translational Research;Translations;Universities;Validation;Variant;Vertebral column

PROJECT_TITLE: Genomics of AML Prognosis

STUDY_SECTION: XNDA

STUDY_SECTION_NAME: Xenobiotic and Nutrient Disposition and Action Study Section[XNDA]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: LEXINGTON

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOCHEMISTRY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE  Colorectal cancer mortality is predominantly due to the development of disseminated disease and resistant to conventional chemotherapy. Our study focuses on developing a mechanistic understanding of PHLPP- mediated regulation of cellular stress signaling to circumvent chemoresistance. Results from our studies will help identify new treatment options and better predict the effectiveness of chemotherapy agents.

PI_NAMEs: GAO, TIANYAN  (contact)

PROGRAM_OFFICER_NAME: SALNIKOW, KONSTANTIN

PROJECT_TERMS: Automobile Driving;Autophagocytosis;biological adaptation to stress;cancer cell;Cancer Etiology;cancer initiation;Cancer Patient;cancer survival;cancer type;Cell Death Induction;cell growth regulation;Cell Migration Inhibition function;Cell Proliferation;Cell Survival;Cells;Cellular Stress;Cessation of life;Chemoresistance;chemotherapy;Collaborations;Colon Carcinoma;colon tumorigenesis;Colorectal Cancer;coping;coping mechanism;Development;Disease;Down-Regulation;Effectiveness;EIF-2alpha;endoplasmic reticulum stress;Ensure;Epithelial Cells;Equilibrium;Event;Funding;Grant;HK2 gene;improved;in vivo;Inflammation;Inflammatory;insight;Integrins;Intestines;Knockout Mice;Knowledge;leucine-rich repeat protein;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Metabolic;Metabolism;Mitochondria;mitochondrial autophagy;Molecular;mortality;mouse model;multicatalytic endopeptidase complex;novel;Oncogenic;Organism;Pathway interactions;PH Domain;Pharmaceutical Preparations;Phosphoric Monoester Hydrolases;Phosphorylation;Physiological;Play;Protein Dephosphorylation;protein expression;Protein Family;Protein Kinase;Protein phosphatase;Proto-Oncogene Proteins c-akt;Regulation;Resistance;response;Role;sensor;Signal Pathway;Signal Transduction;Stress;success;Supporting Cell;Testing;tumor initiation;tumor metabolism;tumor progression;Tumor Suppressor Proteins;tumorigenesis;United States

PROJECT_TITLE: The Role of PHLPP in Colon Cancer

STUDY_SECTION: MONC

STUDY_SECTION_NAME: Molecular Oncogenesis Study Section[MONC]


NIH_SPENDING_CATS: Cancer;Genetics;Hematology;Infectious Diseases;Lymphatic Research;Lymphoma;Rare Diseases

ORG_CITY: LITTLE ROCK

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: PROJECT NARRATIVE Gammaherpesviruses (GHVs) are ubiquitous viruses that establish lifelong chronic infections that can lead to cancer, especially lymphoma. We identified a host protein, p53, as being critical for limiting mutations and cellular transformation due to GHV infection. Experiments are proposed to further define mechanisms of genetic mutations and tumorigenesis that are restricted by p53 during GHV infection, which could identify targets for therapies to prevent or treat GHV-associated lymphomas.

PI_NAMEs: FORREST, JAMES CRAIG (contact)

PROGRAM_OFFICER_NAME: READ-CONNOLE, ELIZABETH LEE

PROJECT_TERMS: Adult;African Burkitt's lymphoma;Agonist;Animal Model;Animals;Apoptosis;B Cell Proliferation;B-Cell Development;B-Cell Lymphomas;B-Lymphocytes;c-myc Proto-Oncogenes;C-Myc Translocation;Cancer Etiology;Cell Cycle Progression;Cell Differentiation process;Cell Proliferation;Cell Survival;cell type;Cells;Chromosomal translocation;Chronic;chronic infection;co-infection;Data;Defense Mechanisms;Dependence;Development;Disease;DNA Damage;DNA Repair;DNA Sequence Alteration;DNA Tumor Viruses;Epstein-Barr virus LMP-1 protein;Epstein-Barr Virus-Related Lymphoma;Event;experimental study;Funding;gammaherpesvirus;Genes;Genetic;Genome;Genomic Instability;Goals;Heavy-Chain Immunoglobulins;Homologous Gene;Human;Human Herpesvirus 4;Human Herpesvirus 8;human pathogen;in vivo;in vivo evaluation;Incidence;infected B cell;Infection;innovation;Integration Host Factors;IRF4 gene;knockout gene;latent infection;Lymphocyte;Lymphoma;Lymphomagenesis;Malaria;Malignant Neoplasms;Mediating;Membrane Proteins;metaplastic cell transformation;Molecular;Mus;Mutate;Mutation;novel therapeutic intervention;Oncogenes;Parasites;pathogen;Pathogenesis;Pathway interactions;Plasmodium;Plasmodium berghei;prevent;Process;Proliferating;promoter;Proteins;Publishing;Reaction;Resistance;response;Risk;Rodent;Sarcoma;Structure of germinal center of lymph node;synergism;System;Systems Analysis;targeted treatment;Testing;Thymic Lymphoma;TP53 gene;tumor;tumorigenesis;Viral;Viral Genes;Viral Proteins;Virus;Virus Latency;Work

PROJECT_TITLE: Defining mechanisms of gammaherpesvirus-driven genomic instability in B cells

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


NIH_SPENDING_CATS: Cancer;Cervical Cancer;HPV and/or Cervical Cancer Vaccines;Immunization;Infectious Diseases;Prevention;Rare Diseases;Sexually Transmitted Infections;Vaccine Related;Women's Health Research

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE  High-risk human papillomaviruses (HPV) cause cervical, anogenital, and head and neck cancers. Despite the availability of preventive HPV vaccines, their poor uptake leaves most men and women at risk for these cancers, many of which remain common globally and others which are increasing domestically. Through direct mechanistic studies of viral and host protein partnerships, this project will uncover how cellular growth and differentiation are hijacked by HPV, and how cellular immortalization is temporally and longitudinally activated by HPV, all of which must occur for HPV-associated cancer development and progression.

PI_NAMEs: KATZENELLENBOGEN, RACHEL ADRIA (contact)

PROJECT_TERMS: Acceleration;Automobile Driving;Binding Proteins;Biological Models;Cancer cell line;cancer initiation;cancer risk;cancer therapy;cancer type;Catalytic Domain;Cell Cycle Arrest;Cell Differentiation process;cell growth;Cell Line;Cell Physiology;Cells;cellular longevity;cellular targeting;Cervical;chronic infection;Chronology;Clinical;clinical risk;Collaborations;Cytoplasm;Data;Development;Differentiation and Growth;Disease;Etiology;Fostering;Future;Gene Targeting;Genetic Transcription;Genome;Goals;Growth;Head and Neck Cancer;high risk;High Risk Woman;HPV-High Risk;Human papilloma virus infection;human papilloma virus oncogene;Human Papilloma Virus Vaccine;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Human papillomavirus 16;Infection;insight;Investigation;keratinocyte;Knock-out;Knowledge;Laboratories;Life Cycle Stages;Link;Longevity;Longitudinal Studies;Maintenance;Malignant neoplasm of cervix uteri;Malignant Neoplasms;men;Molecular;mutant;Oncogenic;Oncogenic Viruses;Oncoproteins;overexpression;Papillomavirus Transforming Protein E6;Pathway interactions;Poly(A)-Binding Proteins;posttranscriptional;prevent;Preventive;Preventive vaccine;protein function;protein protein interaction;Proteins;Regulation;Research;Risk;Risk Factors;senescence;Signal Transduction;Target Populations;Telomerase;TERT gene;therapeutic development;Therapeutic Intervention;Time;tumor progression;tumorigenesis;uptake;Viral;Viral Genes;Viral Markers;Viral Oncogene;Virus;Woman;Work

PROJECT_TITLE: High-risk HPV E6:  dysregulation of immortalization, growth, and differentiation through protein partnerships in HPV-associated cancers


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

ORG_CITY: LA JOLLA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: The proposed research aims to determine how mechanical forces exerted from extracellular matrix in the tumor microenvironment are translated into biochemical signals to promote tumor invasion and metastasis. We believe that this work could uncover a novel regulatory machinery of tumor invasion and provide new targets for anti-metastasis therapy.

PI_NAMEs: YANG, JING  (contact)

PROGRAM_OFFICER_NAME: WOODHOUSE, ELIZABETH

PROJECT_TERMS: 3-Dimensional;arm;Automobile Driving;Biochemical;Breast Cancer Patient;breast cancer progression;cancer cell;Cell Nucleus;clinically significant;Collagen Fiber;Cytoplasm;Data;Distant Metastasis;Ensure;EPHA2 gene;Epithelium;Extracellular Matrix;Family;G3BP1 gene;Genetic Transcription;Goals;Hardness;Human;in vivo;Invaded;Link;LYN gene;Malignant Breast Neoplasm;malignant phenotype;mammary;mammary epithelium;Mammary gland;Mammary Neoplasms;Manuals;mechanical force;mechanical properties;mechanotransduction;Mesenchymal;Molecular;Mus;Neoplasm Metastasis;Nodule;Normal tissue morphology;novel;Nuclear;Nuclear Translocation;Organoids;Outcome;Palpation;Pathway interactions;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Physiological;Play;prevent;Protein Dephosphorylation;Proteins;reconstitution;recruit;Regulation;Research;response;Role;Signal Pathway;Signal Transduction;Site;Testing;therapeutic target;Tissues;transcription factor;Translating;tumor;Tumor Cell Invasion;tumor microenvironment;Tumor Promotion;TWIST1 gene;TYK2;Work

PROJECT_TITLE: Regulation of Tumor Invasion and Metastasis by Matrix Stiffness

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


NIH_SPENDING_CATS: Biotechnology;Cancer;Immunotherapy;Lung;Lung Cancer;Orphan Drug;Rare Diseases

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

ORG_STATE: NY

PHR: The proposed research is directly relevant to public health and NIH’s mission, because our program will result in new functional and mechanistic understanding of immune suppressive mechanisms within tumor microenvironment. This new insight will directly translate into novel immunotherapies for the treatment of cancers.

PI_NAMEs: ZANG, XINGXING  (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Address;Ants;Award;Biology;Bladder;cancer immunotherapy;Cancer Patient;cancer therapy;CAR T cell therapy;CD276 gene;CD28 gene;CD80 gene;Cell Physiology;Cells;Clinical;Clinical Research;clinically significant;Colon;Combined Modality Therapy;Copy Number Polymorphism;CTLA4 gene;cytokine;Data;design;Esophagus;Family;Family member;Foundations;Funding;Gene Dosage;Goals;Grant;Homologous Gene;Human;Immune;immune checkpoint;immune checkpoint blockade;Immune Evasion;Immunosuppression;Immunotherapy;improved;innovation;insight;Islet Cell;Kidney;Legal patent;Liver;Lung Transplantation;Malignant Breast Neoplasm;Malignant neoplasm of brain;Malignant neoplasm of esophagus;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant neoplasm of thyroid;Malignant Neoplasms;Melanoma;member;Mission;Molecular;Monoclonal Antibodies;mouse model;neoplastic cell;new therapeutic target;novel;Outcome;Ovary;overexpression;Pancreas;Pathway interactions;PD-1/PD-L1;Phylogenetic Analysis;programmed cell death ligand 1;programmed cell death protein 1;programs;Prostate;Proteins;Public Health;Publications;receptor;Renal Carcinoma;Research;Skin;Structure;T-Lymphocyte;targeted treatment;Testing;Therapeutic;tool;Transgenic Mice;Translating;Treatment Efficacy;Trees;tumor;Tumor Immunity;tumor microenvironment;tumorigenesis;United States National Institutes of Health;VTCN1 gene

PROJECT_TITLE: The B7x pathways in the tumor microenvironment

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


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

ORG_CITY: CHAPEL HILL

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: RELEVANCE TO PUBLIC HEALTH This project is a continuation of a collaboration which aims to develop new tools and approaches for imaging the microvasculature with ultrasound. Data suggests that imaging the microvasculature will provide us with an improved ability to detect and differentiate cancer in humans, and if successful, our approach may lead to a new low-cost, safe, portable imaging modality that is better at early detection of cancers than currently available modalities. To pursue this, we will develop new ultrasound hardware and imaging approaches, and test their performance in preclinical and clinical populations.

PI_NAMEs: DAYTON, PAUL A (contact)

PROGRAM_OFFICER_NAME: WU, YICONG

PROJECT_TERMS: 3-Dimensional;Achievement;Acoustics;Algorithms;angiogenesis;Angiography;animal imaging;animal tissue;Area;Biological Markers;Biomedical Engineering;Blood Vessels;breast lesion;cancer biomarkers;Clinical;clinical application;clinical imaging;clinical translation;Clinical Trials;Collaborations;contrast enhanced;contrast imaging;Contrast Media;cost;Data;density;design;Detection;Development;Devices;Diagnostic;Disease;Early Diagnosis;fabrication;Frequencies;Future;Genetic Predisposition to Disease;Goals;Human;human imaging;human tissue;Image;imaging approach;imaging modality;Imaging Techniques;Imaging technology;improved;in vivo;indexing;industry partner;innovative technologies;lens;Lesion;Malignant - descriptor;Malignant Breast Neoplasm;Malignant neoplasm of liver;Malignant Neoplasms;Mammary Neoplasms;Mechanics;Microbubbles;Modality;Modeling;molecular imaging;molecular marker;Motion;Mus;new technology;next generation;Noise;novel;Patients;Penetration;Performance;performance tests;Population;portability;pre-clinical;Process;Productivity;prototype;Public Health;Receiver Operating Characteristics;Recovery;Renal Carcinoma;Research;Resolution;Rodent;Screening for cancer;Sensitivity and Specificity;Signal Transduction;spatiotemporal;Specificity;Structure;superresolution imaging;System;Techniques;Technology;Testing;Three-Dimensional Imaging;Time;Tissues;tool;Transducers;Translations;transmission process;treatment response;ultra high resolution;Ultrasonography;ultrasound;Universities;Validation;Visualization;volunteer

PROJECT_TITLE: Academic-Industrial Partnership for Translation of Acoustic Angiography

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Precision Medicine;Prevention;Skin Cancer

ORG_CITY: SALT LAKE CITY

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Project Narrative Melanomas are pigmented skin cancers that can be difficult to distinguish from benign moles, even for trained primary physicians and dermatologists, and can be deadly if overlooked. Based upon the genes and regulatory molecules that distinguish moles from melanomas, the proposed project explores new methods for detecting and preventing the transformation of moles into melanomas.

PI_NAMEs: JUDSON-TORRES, ROBERT LAIRD (contact)

PROGRAM_OFFICER_NAME: WEINREICH, MICHAEL DALE

PROJECT_TERMS: Address;Anatomy;Area;aurora B kinase;Automobile Driving;Benign;benign state;Biological Assay;Biological Models;Biology;Biopsy;BRAF gene;CDKN2A gene;Cell Cycle;Cells;Chemoprevention;Classification;Clinic;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Cutaneous Melanoma;Data;Data Set;Dermatologist;Detection;detection method;Development;Diagnosis;diagnostic accuracy;differential expression;Disease;driver mutation;Drug Delivery Systems;Early Diagnosis;Early identification;early screening;Engineering;Environment;Event;G2/M Arrest;Genes;Genetic;Genetically Engineered Mouse;genomic profiling;Goals;Growth;high risk;high risk population;Histologic;Human;Human Engineering;improved;In Vitro;in vivo;in vivo evaluation;in vivo Model;Incidence;inhibitor;innovation;Interruption;Knowledge;Lesion;Malignant - descriptor;MAP Kinase Gene;Measurement;Mediating;Mediator;melanocyte;Melanocytic nevus;Melanoma;melanoma biomarkers;melanomagenesis;Methods;MicroRNAs;miRNA expression profiling;Modeling;Mole the mammal;Molecular;Molecular Profiling;mRNA Expression;Mutation;Neoplasms;Nevi and Melanomas;Nevus;novel;novel strategies;Oncogenes;Pathologist;Patients;Physicians;Pilot Projects;Positioning Attribute;pre-clinical;prevent;Prevention;Prevention strategy;PTEN gene;Regulation;Reporting;Reproducibility;Role;Sampling;screening;senescence;Signal Transduction;Skin Cancer;skin lesion;Skin Pigmentation;Specificity;Survival Rate;System;Techniques;Testing;Training;Transcript;transcriptomic profiling;tumor;Tumor Suppressor Proteins;Validation

PROJECT_TITLE: Nevus associated microRNAs as mediators of BRAF-induced growth arrest and biomarkers of melanoma progression

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Cancer;Genetics

ORG_DEPT: DENTISTRY

PHR: Identification and characterization of new mechanisms of how the cell responds to DNA damage will significantly impact our understanding of cancer etiology and treatment. The project will reveal novel inter- organelle crosstalk between cytoskeleton factors and DNA damage repair, and thereby, significantly improving our understanding of cancer progression and treatment.

PI_NAMEs: PENG, AIMIN  (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Acetylation;ataxia telangiectasia mutated protein;ATM activation;ATP Hydrolysis;Autophagocytosis;Binding;Biochemical;Biology;Cancer Etiology;cancer therapy;Cell Death Induction;Cell Proliferation;Cell Survival;Cells;Chromatin;chromatin remodeling;Chromatin Remodeling Factor;Chromatin Structure;Clinical;Communication;Complex;condensin;Cytoplasm;Cytoplasmic Structures;Cytoskeleton;Data;Development;DNA;DNA Damage;DNA Double Strand Break;DNA Repair;Double Strand Break Repair;Ensure;Etiology;Event;Exhibits;Family;Genome;genome integrity;Genome Stability;Goals;HDAC1 gene;histone methylation;Homeostasis;Human;human disease;Hypersensitivity;improved;In Vitro;in vivo;innovation;insight;Kinesin;Kinetochores;knock-down;Knock-out;Knowledge;Laboratories;Maintenance Therapy;Malignant Neoplasms;Mediating;member;Microtubule Depolymerization;Microtubule Stabilization;Microtubules;Mitotic;Mobility decline;Modeling;Motor;Movement;mutant;Nonhomologous DNA End Joining;novel;Nuclear;Organelles;Perception;pharmacologic;Phosphorylation;Physical condensation;Play;Poison;Protein Array;protein complex;protein function;protein transport;Proteins;Radiation;recruit;Regimen;Regulation;Relaxation;repaired;Repairosome liposome;response;Role;segregation;Signal Transduction;Site;Therapeutic;therapy outcome;tool;Toxic effect;Tubulin;tumor progression;Vesicle

PROJECT_TITLE: The novel role of microtubule regulators in the DNA damage response

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


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: BIRMINGHAM

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative We want to study the role of adhesion GPCR ADGRB3 as a tumor suppressor in the formation of medulloblastoma, a malignant brain tumor in children. We found that ADGRB3 gene is silenced in the WNT subgroup of medulloblastoma and that reactivation of its expression by epigenetic means has therapeutic benefits. The knowledge derived from these studies may lead to the development of novel epigenetic therapies for brain cancer through the restoration of the ADGRB3 tumor suppressor pathway function.

PI_NAMEs: VAN MEIR, ERWIN G. (contact)

PROGRAM_OFFICER_NAME: OKANO, PAUL

PROJECT_TERMS: Adhesions;antagonist;Attenuated;Behavior;beta catenin;Binding;Binding Proteins;bisulfite sequencing;blood-brain barrier permeabilization;Brain;Brain Stem;cell growth;Cell Proliferation;cell transformation;Cells;Central Nervous System;Central Nervous System Neoplasms;Cerebellar Neoplasms;Cerebellum;chemotherapy;Child;Childhood Brain Neoplasm;Chromatin;Clinical;Clinical Trials;Cognitive;Combination Drug Therapy;CpG Islands;CRISPR/Cas technology;CTNNB1 gene;Data;Data Set;design;Development;developmental neurobiology;DNA Methylation;DNA-Binding Proteins;Dorsal;Epigenetic Process;epigenetic regulation;epigenetic therapy;experimental study;EZH2 gene;G-Protein-Coupled Receptors;Gene Activation;Gene Expression;Gene Expression Profile;Gene Silencing;Genes;Growth;Hippocampus;histone methyltransferase;histone modification;Human;In Vitro;in vivo;inhibitor;insight;Intellectual functioning disability;Knockout Mice;Knowledge;Lip structure;Malignant neoplasm of brain;Malignant neoplasm of central nervous system;MBD2 protein;Mediating;Medulloblastoma;medulloblastoma cell line;member;Methylation;Molecular Profiling;molecular subtypes;Monitor;Morbidity - disease rate;Morphogenesis;mRNA Expression;Mus;mutant;myogenesis;nerve stem cell;Neurologic;Neurological disability;Neurons;Neurosecretory Systems;neurosurgery;novel;novel therapeutic intervention;novel therapeutics;Nude Mice;Oncogenic;Operative Surgical Procedures;Orphan;Outcome Study;Pathway interactions;Patients;Pediatric Neoplasm;pharmacologic;Phosphorylation;physically handicapped;Physiological;Predisposition;promoter;Property;Protein Methyltransferases;Protein Microchips;PTEN gene;Radiation;Radiation therapy;receptor;Regulation;Repression;restoration;Reverse Transcriptase Polymerase Chain Reaction;Role;Scaffolding Protein;Secondary to;Serine;seven-transmembrane G-protein-coupled receptor;SHH gene;side effect;Signal Pathway;Signal Transduction;small molecule;Subgroup;Survival Rate;Survivors;Synaptic plasticity;synaptogenesis;System;Testing;Therapeutic;Therapeutic Effect;Therapeutic Intervention;therapeutically effective;Tissues;transcriptome sequencing;Transgenic Mice;Translations;Treatment Side Effects;tumor;tumor growth;Tumor Suppressor Proteins;tumorigenic;Tumorigenicity;WNT Signaling Pathway;Xenograft procedure;young adult

PROJECT_TITLE: Evaluating ADGRB3 as a tumor suppressor epigenetically silenced in WNT medulloblastoma

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Lung;Lung Cancer;Radiation Oncology

ORG_CITY: PHILADELPHIA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

ORG_STATE: PA

PHR: Our project proposes to form an academic-industrial partnership to translate a novel lung function imaging modality into radiotherapy clinical care for lung cancer patients. The novel lung function imaging modality is referred to as `4DCT-ventilation,' and uses 4-Dimensional CT data along with image processing techniques to innovatively calculate lung functional maps. 4DCT-ventilation has great potential to reduce toxicity and improve outcomes for lung cancer patients undergoing radiation therapy. Our project will develop methods that will enable widespread clinical integration of this novel imaging modality.

PI_NAMEs: CASTILLO, EDWARD ;CASTILLO, RICHARD ;VINOGRADSKIY, YEVGENIY  (contact)

PROGRAM_OFFICER_NAME: KIM, BOKLYE

PROJECT_TERMS: Address;Algorithms;Anatomy;automated segmentation;Cancer Patient;Characteristics;Chest;Clinic;Clinical;clinical care;Clinical Data;clinical practice;Clinical Trials;clinically significant;Commercial grade;community center;Computer software;Data;Data Set;Development;Dose;early phase trial;Engineering;Environment;Evaluation;experience;Feasibility Studies;Four-dimensional;four-dimensional computed tomography;Generations;Heterogeneity;Image;image processing;imaging modality;imaging program;Imaging Techniques;improved;improved outcome;Individual;Industrialization;industry partner;innovation;Institution;Knowledge;Life;Lung;machine learning method;Malignant neoplasm of lung;Maps;Methods;novel;novel imaging technique;Patients;Performance;Physiological;prospective;pulmonary function;quality assurance;Quality of life;Radiation;Radiation Pneumonitis;Radiation therapy;Research;Resolution;Retrospective Studies;Seminal;side effect;software development;Software Tools;standard of care;Study models;System;Techniques;tool;Toxic effect;Translating;Treatment Side Effects;Validation;ventilation

PROJECT_TITLE: Development of a Novel Lung Function Imaging Modality for comprehensive management of lung cancer


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Climate-Related Exposures and Conditions;Genetics;Human Genome;Immunotherapy;Prevention;Skin Cancer

ORG_CITY: Columbus

ORG_DEPT: GENETICS

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: NARRATIVE Major risk factors for melanoma include fair skin and a history of sunburns, yet incomplete understanding of how different skin pigments and types of ultraviolet sunlight (UVA, UVB) contribute to melanoma progression has hindered efforts to curb disease incidence. In this application, we will use models genetically representative of human melanoma to determine how different skin pigments and forms of UV light contribute to melanoma progression. This work will identify deficiencies in the biological mechanisms that protect us from the sun, which could be mitigated to improve melanoma prevention strategies and patient outcomes.

PI_NAMEs: BURD, CHRISTIN E (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: Acceleration;Alleles;Biological;Biological Process;BRAF gene;Cell Line;Cells;combat;Cutaneous Melanoma;Data;Data Set;Development;Disease;Disease Progression;DNA;DNA lesion;DNA Repair;DNA Sequence Alteration;Dose;Etiology;exome sequencing;experimental study;Exposure to;Gene Mutation;Genetic;Genetic Transcription;Genetically Engineered Mouse;Genome;genomic profiling;Genotoxic Stress;Growth;Human;human disease;immune cell infiltrate;Immunotherapeutic agent;improved;in vivo;Incidence;Individual;Intervention;irradiation;Knowledge;Mediating;Melanins;melanocyte;Melanoma;Melanoma Cell;Metabolic;Metastatic Melanoma;Modeling;Mus;Mutagenesis;mutant;mutant mouse model;Mutant Strains Mice;Mutation;Neonatal;Newborn Animals;Nucleotide Excision Repair;Oncogenes;Oxidation-Reduction;Pathology;Pathway interactions;Patient-Focused Outcomes;Pattern;pheomelanin;Physiological;Physiological Processes;Pigmentation physiologic function;Pigments;Prevention strategy;Production;Prognosis;Recording of previous events;Relative Risks;repaired;Research;Residual state;response;Risk;Risk Factors;Role;Site;Skin;Skin Pigmentation;Sun Exposure;Sunburn;Sunlight;Sunscreening Agents;System;Testing;the sun;Transcription-Coupled Repair;transcriptome sequencing;transcriptomics;tumor;tumor growth;tumor microenvironment;tumorigenesis;tumorigenic;ultraviolet;Ultraviolet A radiation;Ultraviolet B Radiation;ultraviolet damage;ultraviolet lesions;Ultraviolet Rays;UV carcinogenesis;UV Mutagenesis;UV protection;UV Radiation Exposure;UV response;Work

PROJECT_TITLE: Mechanisms of UV-Mediated Melanoma Development


NIH_SPENDING_CATS: Biotechnology;Cancer;Lung;Lung Cancer;Orphan Drug;Rare Diseases

ORG_CITY: LOS ANGELES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative  Cancers use two different types of transporters to take up the glucose they need to grow: SGLT2 and GLUT1; we found that early-stage lung cancers use SGLT2, while more advanced lesions switch to GLUT1. We are going to investigate the metabolic function of the switch between SGLT2 and GLUT1, and the mechanisms by which the cells can induce this switch. This is relevant because metabolic inhibition is at the basis of novel targeted therapies for lung cancer, but the switch from one transporter to the other represents a strategy of cancer cells to develop resistance to therapy, which needs to be addressed in order to improve patient survival.

PI_NAMEs: SCAFOGLIO, CLAUDIO  (contact)

PROGRAM_OFFICER_NAME: WILLIS, KRISTINE AMALEE

PROJECT_TERMS: Address;aerobic glycolysis;Agreement;Area;Biological;cancer cell;Cancer Etiology;cancer therapy;Carcinoma;Cell Differentiation process;Cell Line;Cell Respiration;Cells;Cellular Metabolic Process;Cessation of life;Clustered Regularly Interspaced Short Palindromic Repeats;constitutive expression;Coupled;Data;Development;Distal;Engineering;Evaluation;fluorodeoxyglucose;Genetically Engineered Mouse;Glucose;glucose metabolism;glucose transport;Glucose Transporter;glucose uptake;Glutamine;glycogen synthase kinase 3 beta;Glycolysis;Goals;Growth;Heterogeneity;HIF1A gene;Histology;Hypoxia;Hypoxia Inducible Factor;Immunohistochemistry;improved;In Vitro;in vivo;inhibitor;Insulin;Knock-out;Lesion;Lung;Lung Adenocarcinoma;lung carcinogenesis;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Mediating;Membrane Potentials;Metabolic;metabolic phenotype;Metabolism;metabolomics;Mitochondria;mitochondrial membrane;mitochondrial metabolism;Modality;Molecular;Morphology;Mus;new therapeutic target;Nodule;novel;novel therapeutics;overexpression;Pathogenesis;Pathway interactions;patient derived xenograft model;Patients;pharmacologic;Phenotype;Phosphotransferases;Pimonidazole;Play;Population;Positron-Emission Tomography;premalignant;progenitor;programs;Proto-Oncogene Proteins c-akt;Regulation;Research;Resistance development;resistance mechanism;Role;SLC2A1 gene;Sodium;Spirometry;System;Testing;therapy resistant;tool;TP53 gene;Tracer;transcriptomics;transgene expression;treatment response;tumor;tumor growth;Tumor stage;uptake;Warburg Effect

PROJECT_TITLE: Investigating the heterogeneity of glucose transport in lung adenocarcinoma

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Pancreatic Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: PATHOLOGY

PHR: Project narrative Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy with a five-year survival of less than 5%. Genomic analyses of human samples suggest that PDAC can be classified into at least two major subtypes based on cancer cell autonomous properties. The proposed research will investigate the molecular regulators of PDAC subtype and provide fundamental knowledge required for the design of therapeutic strategies that target PDAC on the basis of subtype-specific vulnerabilities.

PI_NAMEs: SNYDER, ERIC LEE (contact)

PROGRAM_OFFICER_NAME: FINGERMAN, IAN M

PROJECT_TERMS: ATAC-seq;Biology;cancer cell;Cell Line;cell regeneration;chemotherapy;ChIP-seq;Classification;clinically relevant;cofactor;Data;design;Development;differential expression;Differentiation and Growth;Disease;Exhibits;experimental study;Family;Gene Expression;gene regulatory network;Genes;Genetically Engineered Mouse;Genomics;Goals;Growth;HNF4A gene;Homeobox;Human;In Vitro;in vitro Model;in vivo;insight;Knowledge;loss of function;Lysine;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Measures;member;Mesenchymal;Molecular;molecular subtypes;mouse model;Mus;muscle progenitor cell;Normal tissue morphology;novel;Oncogenes;Organoids;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;patient derived xenograft model;Pattern;Pharmaceutical Preparations;Play;Primitive foregut structure;progenitor;Prognosis;programs;Proliferating;promoter;Property;Protein Isoforms;Repression;Research;response;restraint;Role;Sampling;Specific qualifier value;stem cell function;stem cell proliferation;System;Testing;Therapeutic;Tissues;transcription factor;transcriptome;transcriptomics;tumor;tumor growth;Work

PROJECT_TITLE: Lineage specifiers governing pancreatic cancer growth and molecular subtype


NIH_SPENDING_CATS: Aging;Breast Cancer;Cancer;Clinical Research;Prevention;Women's Health Research

ORG_CITY: JACKSONVILLE

ORG_NAME: MAYO CLINIC  JACKSONVILLE

ORG_STATE: FL

PHR: PROJECT NARRATIVE By analyzing tissue samples from benign breast biopsies, we have found that more than 40% of postmenopausal women have incomplete lobular involution, and that these women are at substantially greater risk for subsequently developing cancer. Our project will provide insight into the previously unstudied mechanisms that control lobular involution and will define why postmenopausal women who have not completed the process of lobular involution are at greater risk for breast cancer development. This research will be crucial for better guiding women who obtain breast biopsies toward the most appropriate strategies of surveillance, risk management, and treatment, and will also point towards new physiologic strategies to reduce breast cancer incidence, including the induction of lobular involution in postmenopausal women for whom this process is incomplete.

PI_NAMEs: DEGNIM, AMY C;RADISKY, DEREK C (contact);SHERMAN, MARK E

PROGRAM_OFFICER_NAME: PATRIOTIS, CHRISTOS F

PROJECT_TERMS: Abbreviations;Address;Affect;African American Women;Age;age related;Aging;Benign;benign state;Biological;Biological Markers;biomarker identification;Biopsy;Black race;Breast;Breast biopsy;Breast Cancer Prevention;Breast Cancer Risk Factor;Breast Diseases;Breast Epithelial Cells;cancer risk;case control;Caucasians;Cell Separation;Cells;child bearing;Classification;Clinic;Clinical;cohort;Control Groups;Cytometry;Data;data integration;Development;Epithelial Cells;Epithelium;Evaluation;Experimental Models;experimental study;Future;Goals;high risk;Human;human disease;humanized mouse;Immunohistochemistry;improved;Incidence;innovation;insight;Investigation;Knowledge;Lactation;Link;Lobular;Lobule;Malignant Breast Neoplasm;Malignant Neoplasms;mammary epithelium;Mammary Gland Parenchyma;Mediator;Methods;milk production;Modeling;Molecular;mouse model;Myoepithelial cell;nano-string;novel;Pathway interactions;Patients;Perimenopause;periostin;Phenotype;Physiological;Physiological Processes;Population;Population Heterogeneity;Postmenopause;predictive marker;Prevention;Process;Proliferating;Publishing;Race;Research;Research Design;Risk;Risk Assessment;Risk Management;risk prediction;Signal Pathway;Site;Source;Structure;surveillance strategy;Testing;Time;Tissue Sample;White Women;WNT Signaling Pathway;Woman;women's diagnosis;Work;Xenograft Model

PROJECT_TITLE: Involution-based biomarkers of breast cancer risk

STUDY_SECTION: CBSS

STUDY_SECTION_NAME: Cancer Biomarkers Study Section[CBSS]


ORG_CITY: NEW HAVEN

ORG_DEPT: SURGERY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative The vast majority of new cancer drugs fail to significantly help the patients who try them. We believe that this is in part because the targets of these drugs have not been determined correctly. We will use a set of genetic techniques to discover the real targets of several different cancer drugs, which may help clinicians identify which patients would be most likely to benefit from receiving them.

PI_NAMEs: SHELTZER, JASON  (contact)

PROGRAM_OFFICER_NAME: VENKATACHALAM, SUNDARESAN

PROJECT_TERMS: Ablation;Alleles;anti-cancer research;Antineoplastic Agents;Biological Assay;Biological Markers;biomarker identification;cancer cell;cancer genetics;cancer therapy;Cell Cycle;Cell Cycle Progression;Cell Death Induction;cell killing;Cell Line;Cell Proliferation;Cells;cellular targeting;Chemicals;Clinical;clinical efficacy;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Combined Modality Therapy;Coupled;CRISPR/Cas technology;Cyclin-Dependent Kinase Inhibitor;Dependence;Dose;Dose Limiting;Drug Design;drug isolation;drug repurposing;Drug resistance;Drug Targeting;Essential Genes;Evaluation;Exhibits;experimental study;Failure;fitness;Genes;Genetic;genetic architecture;Genetic Screening;Genetic Techniques;genetic technology;Goals;Growth;Human;In Vitro;in vivo;Induction of Apoptosis;inhibitor;knock-down;Knock-out;Knowledge;Laboratories;loss of function;Malignant - descriptor;Malignant Neoplasms;Mitotic;Mitotic Cell Cycle;Modeling;Mutagenesis;Mutation;novel;novel anticancer drug;novel therapeutics;null mutation;Oncology;patient population;Patients;Pharmaceutical Preparations;pharmacologic;Phenotype;Phosphotransferases;pre-clinical;Prediction of Response to Therapy;Proliferating;Proteins;Publishing;Reagent;Regimen;Reporting;Research;research clinical testing;Resistance;resistance mutation;response;RNA Interference;Role;Series;side effect;small molecule;small molecule inhibitor;Specificity;targeted treatment;Techniques;Testing;Therapeutic;Therapeutic Intervention;Tissues;Toxic effect;tumor;tumorigenesis;Validation;Work

PROJECT_TITLE: Discovering the mechanisms of-action-mistargeted anti-cancer agents


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Coronaviruses;Dental, Oral, and Craniofacial Disease;Emerging Infectious Diseases;Genetics;Human Genome;Infectious Diseases;Neurosciences;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

ORG_CITY: DURHAM

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: DUKE UNIVERSITY

PHR: Project Narrative The proposed research is relevant to public health because it seeks to define human odor-induced alterations in olfactory cells in normal or diseased conditions. Proposed experiments will combine a biopsy-based approach and single cell assays to define mechanisms driving olfactory neuronal homeostasis and dysfunction. The project is relevant to the NIDCD’s mission because it addresses chemosensory disorders in humans.

PI_NAMEs: DATTA, SANDEEP R;GOLDSTEIN, BRADLEY J (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, SUSAN L

PROJECT_TERMS: Acute;Address;Anosmia;Area;Automobile Driving;Biopsy;Cell surface;cell type;Cells;Cellular Assay;Chronic;Clinical Research;Code;Communities;COVID-19 associated anosmia;Data;Data Set;Detection;Disease;effective therapy;Epithelium;experimental study;Exposure to;flexibility;Functional disorder;Future;Gene Expression;Gene Expression Profile;gene function;Genes;Genetic Transcription;genome-wide;Health;Homeostasis;Housing;Human;Human Biology;human subject;hyposmia;in vivo;Individual;Infection;Inflammation;Ligands;Measures;Methods;minimally invasive;Mission;Modeling;Molecular;Molecular Biology;Mus;National Institute on Deafness and Other Communication Disorders;Neurobiology;Neurons;Nose;novel;novel strategies;Odors;olfactory bulb;olfactory disorder;Olfactory Epithelium;Olfactory Mucosa;olfactory receptor;olfactory sensory neurons;Organ;Paraosmias;Pathogenicity;Patients;Peripheral;Persons;Population;Positioning Attribute;post-COVID-19;Process;programs;Property;Public Health;receptor;Recovery;recruit;Research;response;Rodent;Sampling;Sensory;Sensory Disorders;Signal Transduction;single cell sequencing;single-cell RNA sequencing;Smell Perception;smell test;Specific qualifier value;Supporting Cell;sustentacular cell;Testing;Toxin;transcriptome;Translating;Trauma;Variant;Work

PROJECT_TITLE: Towards a molecular biology of human olfaction in health and disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICN-T (02)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Precision Medicine;Skin Cancer

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project narrative Targeted therapies for melanoma promise to eradicate melanoma, but drug resistance remains an impediment to cures. We have developed approaches to analyzing the specific subpopulations of cancer that are resistant to drug, and are identifying the molecular pathways we can exploit to block resistant cells from forming.

PI_NAMEs: HERLYN, MEENHARD F;RAJ, ARJUN  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Affect;Bar Codes;Biological;Biology;BRAF gene;cancer cell;cancer drug resistance;Categories;Cell Line;Cell Survival;Cells;cellular transduction;Combined Modality Therapy;Complement;CRISPR/Cas technology;Development;Distant;DNA;Drug resistance;Epigenetic Process;Evolution;Gene Expression;Genes;genome-wide;Growth;Human;human model;Image;Immunotherapy;In Vitro;in vivo;in vivo Model;Individual;inhibitor;inhibitor therapy;kinase inhibitor;Libraries;MAP2K1 gene;MAP3K1 gene;MEKs;Melanoma;Melanoma Cell;Minor;Modeling;Molecular;Molecular Target;mouse model;mutant;Mutation;Nature;neoplastic cell;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Organ;Pathway interactions;patient derived xenograft model;Patients;Pattern;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Population;preclinical study;programs;Proliferating;rational design;Relapse;relapse patients;repository;Resistance;Resistance development;resistance mechanism;Resistance Process;response;RNA;RNA analysis;Signal Pathway;single-cell RNA sequencing;Specimen;System;targeted treatment;Testing;Therapeutic;three dimensional cell culture;Time;transcriptomics;Treatment outcome;treatment response;treatment strategy;tumor;Tumor Cell Line;tumor heterogeneity;Validation

PROJECT_TITLE: Understanding and Overcoming Resistance to BRAF/MEK Kinase Inhibitors in Melanoma


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Human Genome;Infectious Diseases;Precision Medicine;Radiation Oncology;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) treated with a high dose of radiation (70 Gy) has an excellent chance to be cured, but the high radiation dose has significant side effects. The goal of this proposal is to evaluate how well a significantly reduced dose of radiation (30 Gy) can control and cure cancer in certain patients with HPV-positive OPC. These patients will be selected based on the level of oxygen in their tumors, as tumors with low levels of oxygen (hypoxia) often do not respond as well to radiation treatment as those with higher levels of oxygen; and in patients without hypoxic tumors, evidence has shown that the reduced dose of radiation may work just as well and without the severe side effects.

PI_NAMEs: LEE, NANCY Y (contact)

PROGRAM_OFFICER_NAME: VIKRAM, BHADRASAIN

PROJECT_TERMS: Aftercare;American Joint Committee on Cancer;Beds;Biological;Biological Markers;biomarker discovery;Cancer Biology;cancer classification;Cancer Patient;candidate identification;Cellularity;Cetuximab;chemoradiation;chemotherapy;Cisplatin;Clinical;Clinical Data;cohort;Data;Defect;Deglutition;Deglutition Disorders;Diffusion;Diffusion Magnetic Resonance Imaging;Disease;disorder control;DNA;DNA Damage;Dose;Double Strand Break Repair;Eligibility Determination;Ensure;Excision;experience;fluorodeoxyglucose positron emission tomography;Functional disorder;Gene Expression;Gene Expression Profiling;Genes;genome sequencing;genomic signature;Genomics;Goals;HPV oropharyngeal cancer;Human Papillomavirus;Hypoxia;Image;imaging biomarker;In complete remission;Individual;Inferior;Left;Lesion;Magnetic Resonance Imaging;Malignant neoplasm of anus;Malignant Neoplasms;Measures;Methods;Molecular;Monitor;Morbidity - disease rate;Motion;Mucositis;Mutation;Nature;Neck Dissection;Nodal;non-invasive imaging;Normal tissue morphology;novel;Operative Surgical Procedures;overtreatment;Oxygen;Pathologic;Pathway interactions;Patient Selection;patient stratification;Patients;personalized approach;PET/CT scan;Pilot Projects;pilot trial;Positron-Emission Tomography;Postoperative Period;pre-clinical;primary endpoint;Primary Neoplasm;Process;Prognosis;Progression-Free Survivals;quantitative imaging;Radiation;Radiation Dose Unit;radiation resistance;Radiation therapy;Radiation Tolerance;randomized trial;Research;Resolution;response;side effect;Statistical Models;Structure;Survival Rate;Tissues;tool;Toxic effect;Treatment outcome;treatment response;Treatment-related toxicity;tumor;tumor hypoxia;tumor microenvironment;Virus Integration;Virus Replication;whole genome;Work

PROJECT_TITLE: A personalized approach using hypoxia resolution to guide curative-intent radiation dose reduction to 30 Gy: A novel de-escalation paradigm for HPV-associated oropharynx cancers

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


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

ORG_CITY: SAN ANTONIO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: Project Narrative Cancer cells use various mechanisms to manage their survival such as repairing DNA damage resulting from unchecked DNA replication. Moreover, the ability of cancer cells to repair radiation or chemotherapy drug- induced DNA damage also serves as one of the mechanisms for therapy resistance. Consistent with this, several DNA repair factors are reported to be overexpressed in cancer patients. Therefore, drugs that are capable of suppressing DNA repair responses of cancer cells will have promising therapeutic outcomes. This study proposes to develop a novel inhibitor that is derived from a FDA approved anti-depressant, which will suppress breast cancer growth and metastasis by inhibiting key proteins such as FOXM1, which are involved in DNA repair pathway. Furthermore, this inhibitor has potential to enhance the efficacy of the current chemotherapy drugs and prolong survival of breast cancer patients.

PI_NAMEs: RAO, MANJEET KUMAR (contact);VADLAMUDI, RATNA K

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: aggressive breast cancer;analog;anti-depressive agents;Anti-estrogen Therapy;Binding;Biochemical;Biological Assay;Biophysics;BRCA1 gene;Breast Cancer Patient;breast cancer progression;breast cancer survival;cancer addiction;cancer cell;Cancer Center;Cancer Patient;cancer subtypes;Cell model;Cells;chemotherapy;Chemotherapy and/or radiation;Clinic;Clinical;clinical development;Confocal Microscopy;coping;Defect;Distant Metastasis;DNA;DNA biosynthesis;DNA Damage;DNA Repair;DNA Repair Gene;DNA Repair Pathway;drug development;Endocrine;Estrogen receptor positive;Excision Repair;FDA approved;Feedback;FOXM1 gene;Funding;Future;Genes;genotoxicity;Goals;Growth;homologous recombination;hormone therapy;Human;humanized mouse;Imipramine;Immune;Immunofluorescence Immunologic;improved;inhibitor;innovation;knock-down;Legal patent;Lesion;Malignant Breast Neoplasm;Malignant Neoplasms;Modeling;Molecular Biology;Mutation;Neoplasm Metastasis;Nodal;Nonhomologous DNA End Joining;Normal Cell;novel;novel therapeutics;Oncogenic;Outcome;overexpression;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;Phase I Clinical Trials;Play;Positioning Attribute;Predisposing Factor;Privatization;programs;Proliferating;Proteins;Regimen;Relapse;repaired;Reporting;Resistance;response;Role;safety testing;Signal Transduction;Structure;Tamoxifen;targeted treatment;Testing;Therapeutic;therapeutic evaluation;therapeutic target;therapy development;therapy outcome;therapy resistant;Toxic effect;Translating;translational potential;treatment response;triple-negative invasive breast carcinoma;tumor;tumor xenograft;Xenograft Model;Xenograft procedure

PROJECT_TITLE: FoXM1 inhibition: a novel therapeutic avenue to treat breast cancers


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Services;Nutrition;Obesity;Pediatric;Pediatric Cancer;Physical Activity;Prevention;Rare Diseases

ORG_CITY: TAMPA

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

PHR: Project Narrative Approximately 40-50% of off-treatment pediatric cancer survivors (PCS) are overweight or obese; thereby increasing their risk for negative long-term physical health complications. Using our successful pilot trial testing the preliminary feasibility and efficacy of NOURISH-for Healthy Transitions (NOURISH-T, 5R21CA167259) as a base, we address obesity in PCS by targeting parents as agents for change in modeling healthy eating and physical activity behaviors to promote positive PCS health behavior change and long-term healthy weight. This multi-site application addresses the public health epidemic of obesity by conducting a randomized control trial to test the efficacy of our intervention, NOURISH-T+, across a diverse sample of PCS and their parents at four pediatric oncology clinics, with the goal of establishing a framework for future translation and dissemination of NOURISH-T+.

PI_NAMEs: STERN, MARILYN  (contact)

PROGRAM_OFFICER_NAME: AGURS-COLLINS, TANYA

PROJECT_TERMS: Accelerometer;acceptability and feasibility;Address;Adherence;adult obesity;Aftercare;Age;base;Behavior;behavior change;Behavioral;Blinded;Body mass index;Body Weight decreased;cancer therapy;Cardiovascular Diseases;Characteristics;Child;Child health care;Childhood;childhood cancer survivor;Childhood Cancer Treatment;Chronic Disease;Clinic;clinical practice;Collaborations;Data;Data Analyses;data management;Diabetes Mellitus;dietary;Dietary Assessment;Eating;Eating Behavior;effectiveness evaluation;Effectiveness of Interventions;efficacy evaluation;efficacy testing;Energy Intake;Enrollment;ethnic diversity;Exercise;Family;Fatty acid glycerol esters;Florida;follow-up;Frequencies;Future;Goals;Health;Health behavior change;Healthcare Systems;Healthy Eating;healthy weight;Height;high risk population;Hour;improved;Intake;Intervention;intervention delivery;Late Effects;Maintenance;Manuals;Measures;Medical center;Metabolic syndrome;Modeling;modifiable behavior;Obesity;Obesity Epidemic;obesity in children;obesity risk;obesity treatment;Outcome;Overweight;Pamphlets;Parents;Participant;Patient Recruitments;Patient Self-Report;Pediatric Hospitals;Pediatric Oncology;Perception;Physical activity;physical conditioning;pilot trial;Population;post intervention;Preventive;primary outcome;Public Health;racial diversity;Randomized;Randomized, Controlled Trials;Recording of previous events;recruit;Reporting;Research;Research Personnel;Risk;Risk Reduction;role model;Sampling;secondary outcome;sedentary activity;Siblings;Site;sugar;Survivors;survivorship;Testing;Time;Translations;treatment as usual;Universities;Videoconferencing;Virginia;Vulnerable Populations;Waist-Hip Ratio;Weight;Weight Gain;Work;young adult

PROJECT_TITLE: NOURISH-T+: A Randomized Control Trial Targeting Parents in Promoting Healthy Eating and Exercise Behaviors in Pediatric Cancer Survivors with Overweight/Obesity

STUDY_SECTION: PDRP

STUDY_SECTION_NAME: Psychosocial Development, Risk and Prevention Study Section[PDRP]


NIH_SPENDING_CATS: Biotechnology;Cancer;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: High grade serous cancers arise in the fallopian tube and exhibit a high proclivity to metastasize to the ovary as their primary metastatic site and omentum as a secondary site. Our team developed novel imaging mass spectrometry workflows to interrogate 3D organ culture systems co-cultured with fallopian tube derived tumor models to study the chemical crosstalk that occurs during metastasis. Overall, these data provide important new tools to uncover the signaling that occurs between organs and cells as it relates to the ovarian microenvironment in high grade serous metastasis.

PI_NAMEs: BURDETTE, JOANNA E (contact);SANCHEZ, LAURA MARGARET

PROGRAM_OFFICER_NAME: DUECK, HANNAH RUTH

PROJECT_TERMS: 3-Dimensional;Adhesions;Adrenergic Antagonists;Adrenergic beta-Antagonists;Adrenergic Receptor;Anatomy;Automobile Driving;beta-adrenergic receptor;Biological;Biological Assay;Biological Models;Biology;cancer cell;Cell Communication;Cell model;Cells;Cessation of life;Chemicals;Chemistry;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Communication;Consumption;Data;Detection;Development;Disease;Emerging Technologies;Epithelial Cells;Epithelium;Equipment and supply inventories;Event;Exhibits;folate-binding protein;Folic Acid;Freezing;Genetic;Glycogen;Human;in vivo;innovation;Invaded;Ions;Knock-out;Ligands;Lipids;Location;Malignant neoplasm of ovary;Malignant Neoplasms;Mammalian Oviducts;mass spectrometric imaging;Measures;Mediating;metabolome;metabolomics;Metastatic Malignant Neoplasm to the Ovary;Methodological Studies;migration;Modeling;mortality;Mus;Mutation;Names;Neoplasm Metastasis;neoplastic cell;Newly Diagnosed;Norepinephrine;novel;Omentum;Organ;Organ Culture Techniques;Ovarian;Ovary;overexpression;Pathway interactions;Patient-Focused Outcomes;Peritoneal;Peritoneum;Process;Production;Protein Secretion;Proteins;Proteomics;Protocols documentation;Role;Route;Sampling;Series;Serous;Signal Pathway;Signal Transduction;Site;small molecule;Source;Spatial Distribution;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;spheroids;System;Techniques;Technology;Testing;therapeutic target;three dimensional cell culture;Time;Tissues;tool;Translating;tumor;Tumor Cell Invasion;Tumor Cell Migration;Tumor Expansion;tumorigenic;Work;Xenograft procedure

PROJECT_TITLE: Imaging mass spectrometry methodologies for studying the metabolites of cancer metastasis


NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Lung Cancer;Neurosciences;Prevention;Social Determinants of Health;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: EUGENE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: 8. Project Narrative Cigarette smoking is among the leading causes of preventable death in the United States because smoking increases risk for lung cancer and various diseases. Though U.S. smoking rates have declined, a substantial percentage of adults, particularly those living in poverty who have repeatedly tried and failed to quit, still smoke and therefore could benefit from novel interventions for cessation that operate through different mechanisms than those of traditional treatments. This study will use neuroimaging to uncover the mechanisms of action of a promising strategy for affect regulation and smoking cessation and also build profiles of individuals for whom this strategy does and does not work, thereby providing tangible and practical information that public health professionals and clinicians can use to inform personalized treatments for cigarette smoking cessation.

PI_NAMEs: BERKMAN, ELLIOT TODD (contact)

PROGRAM_OFFICER_NAME: FERRER, REBECCA

PROJECT_TERMS: Abstinence;Adult;Affect;Affective;arm;Behavior;Cancer Control;Cigarette;cigarette craving;Cigarette Smoker;cigarette smoking;cognitive process;cognitive reappraisal;cost;craving;Data;Decision Making;Disease;Down-Regulation;efficacy trial;Event;experience;experimental study;fighting;Fire - disasters;Functional Magnetic Resonance Imaging;Future;Goals;Health behavior;Health Professional;Health Promotion;Individual;Individual Differences;Informal Social Control;insight;Intervention;Knowledge;Lateral;lens;Light;Machine Learning;Malignant neoplasm of lung;Malignant Neoplasms;Medial;Motivation;Multivariate Analysis;neural;neuroimaging;neuromechanism;Neurophysiology - biologic function;novel;Participant;Pathway interactions;Pattern;Personality Traits;personalized medicine;personalized strategies;Persons;Poverty;preventable death;Process;Provider;Psychology;Public Health;Regulation;Reporting;Research;response;Risk;Sample Size;Sampling;Scanning;Science;Smoke;Smoker;Smoking;smoking cessation;Stimulus;System;Techniques;Testing;Theoretical model;theories;Time;tobacco control;tool;Training;treatment as usual;treatment response;Triage;United States;Up-Regulation;Work

PROJECT_TITLE: Construal level as a novel pathway for affect regulation and cancer control

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


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

ORG_CITY: WASHINGTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: Project Narrative  Cancer is a leading cause of death worldwide, and lymphoma is one of the most common form of blood cancers in the world. An understanding of HDAC11's role in regulating anti-cancer immunity will pave the way for developing potential new strategies to treat lymphoma patients. The proposed research is relevant to the NCI's mission to develop fundamental strategies and acquire knowledge that will improve healthcare and alleviate human suffering from cancer.

PI_NAMEs: LI, RONG ;LIN, HENING ;SETO, EDWARD  (contact)

PROJECT_TERMS: Acceleration;acyl group;Acylation;anti-cancer;anti-tumor immune response;Antigen-Presenting Cells;Antitumor Response;B lymphoid malignancy;Cancer Model;cancer therapy;Cause of Death;cdc42 GTP-Binding Protein;Cell Cycle;Cell Line;cell motility;Cell Physiology;Cell Polarity;Cells;Chemicals;Collaborations;Complex;cytokine;Data;Deacetylase;Deacetylation;Development;Disease;Enzyme Inhibitor Drugs;Enzymes;Excision;Family;fatty acylation;Functional disorder;Genetic Models;Glycine Hydroxymethyltransferase;Goals;Growth;HDAC11 gene;Healthcare;Hematologic Neoplasms;Hematopoietic Neoplasms;Histone Deacetylase;Histone Deacetylase Inhibitor;Human;IFNAR1 gene;Immune;immune function;Immune response;Immune signaling;Immune system;Immunity;immunoregulation;Immunotherapy;improved;In Vitro;in vivo;Individual;Infiltration;Inflammatory;inhibitor;insight;Interferon Type I;Interferons;Interleukin-10;isopeptidase;Knock-out;Knockout Mice;Knowledge acquisition;Laboratories;lymph nodes;Lymphoid Tissue;Lymphoma;Lymphoma cell;Lysine;Malignant Neoplasms;Mantle Cell Lymphoma;Mediating;Mediator;migration;Mission;Modeling;Molecular;Monomeric GTP-Binding Proteins;mouse model;multidisciplinary;Mus;neutrophil;new therapeutic target;Non-Hodgkin's Lymphoma;novel;novel drug class;novel therapeutics;Patients;Phagocytes;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacotherapy;Physiological;Play;Positioning Attribute;Predisposition;Process;Production;programs;Proliferating;Property;protein function;Proteins;Refractory;Regulation;Regulatory T-Lymphocyte;Research;Research Personnel;rho;Role;Signal Transduction;Site;T-Lymphocyte;Testing;Therapeutic;Therapeutic Effect;tool;Transplantation;treatment strategy;tumor;tumor behavior;tumor growth;Tumor Immunity;tumor microenvironment;Tumor-infiltrating immune cells;tumorigenesis;tumorigenic;United States;Universities;Washington;Wild Type Mouse;Work

PROJECT_TITLE: Regulation of anti-tumor immunity by HDAC11

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


ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Narrative Obesity will soon be the leading cause of preventable cancers and a large proportion of cancer patients are obese, but little is understood about how obesity influences the effectiveness of cancer therapy. Clinical studies as well as our pre-clinical data show that obese cancer patients are more resistant to radiotherapy and have higher rates of cancer recurrence. Based on our previous data showing that obesity profoundly impacts tumor biology we will examine mechanisms inducing radiotherapy resistance and how to improve outcomes in obese patients.

PI_NAMEs: MONJAZEB, ARTA MONIR (contact)

PROGRAM_OFFICER_NAME: PRASANNA, PAT G

PROJECT_TERMS: Address;adipokines;Adoptive Transfer;Affect;antitumor effect;Apoptotic;BCL2 gene;Biological;cancer cell;cancer infiltrating T cells;Cancer Model;Cancer Patient;cancer recurrence;cancer survival;cancer therapy;Cell Proliferation;Clinical;Clinical Data;Clinical Research;Data;diet-induced obesity;Dose;Effectiveness;exhaustion;Fractionated radiotherapy;Functional disorder;Genes;Hormonal Change;Hormones;Immune;Immune response;Immune system;Immune System Diseases;immunosuppressed;Implant;improved;improved outcome;In Vitro;in vivo;Inflammation;Knowledge;Leptin;Link;Malignant Neoplasms;Mediating;Metabolic;Modeling;mouse model;Mus;Obese Mice;obese patients;Obesity;obesity treatment;Outcome;pandemic disease;Patients;personalized medicine;Phenotype;pre-clinical;preclinical study;Preventable cancer cause;Production;Proliferating;Publishing;radiation delivery;Radiation Physics;radiation resistance;radiation response;Radiation therapy;Recurrence;Regulation;Resistance;response;Signal Transduction;Smoking;survivin;T-Lymphocyte;Testing;therapy outcome;Thinness;Toxic effect;Treatment Efficacy;treatment response;treatment strategy;tumor;Tumor Biology;tumor growth;Tumor Immunity;tumor metabolism;tumor microenvironment;United States;Up-Regulation

PROJECT_TITLE: The Impact of Obesity on Radiotherapy Anti-Tumor Effects


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

PHR: Narrative It is well established that Ewing sarcoma is driven by a fusion oncogene, EWSR1-FLI1, however the biology of this oncogene is poorly understood. In our prior work we identified that EWSR1-FLI1 dysregulates a fundamental process, transcription, causing an increase in R-loops. While R-loops serve normal functions, high levels of R-loops are considered deleterious and are often associated with genome instability and a loss of cellular fitness. The mechanism of how Ewing sarcoma is able to maintain high levels of R-loops without genomic instability is not known. If we can determine this mechanism, then we should be able to specifically target it as an alternate therapy for the treatment of Ewing sarcoma.

PI_NAMEs: BISHOP, ALEXANDER JAMES (contact)

PROJECT_TERMS: Acute;Alternative Splicing;Binding;Biological Assay;Biology;BRCA1 gene;cDNA Expression;Cell Cycle;Cell Cycle Progression;Cell Physiology;cell type;Cells;Chemicals;Childhood;Chimeric Proteins;ChIP-seq;comparison control;Data;Data Analyses;Defect;DNA Damage;DNA Repair;efficacy testing;Ewings sarcoma;EWSR1 gene;fitness;FLI1 gene;Genes;Genetic;Genetic Transcription;Genome;Genome Stability;genome-wide;Genomic Instability;Genomics;global run on sequencing;Goals;Growth;helicase;Impairment;in vivo;inhibitor;insight;interest;Intervention;Lesion;Link;Location;Malignant Childhood Neoplasm;Malignant Neoplasms;Measures;Modeling;Molecular;Monitor;Nature;Oncogenes;Paper;Pathologic;Pathway interactions;Pharmacologic Substance;Phenotype;Physiological;prevent;Process;programs;protein function;Proteins;Publishing;replication stress;Reporter;Reporting;Resolution;response;RNA;RNA helicase A;RNA Interference;RNA metabolism;RNA Polymerase II;RNA Processing;RNA Splicing;Role;SETX gene;single cell sequencing;Site;Small Interfering RNA;stem cells;targeted treatment;Techniques;Testing;Text;Therapeutic;Time;Toxic effect;Transcription Process;transcriptome sequencing;tumor;tumor growth;tumor xenograft;Uridine;Work;young adult

PROJECT_TITLE: Dysregulated transcription processes in Ewing sarcoma


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Urologic Diseases

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: We will assess how two different chemotherapy regimens with therapeutic equipoise, MVAC and GC, affect the immune microenvironment of bladder cancer as well as assess their ability to potentiate the effects of immune checkpoint blockade.

PI_NAMEs: KIM, WILLIAM Y. (contact);VINCENT, BENJAMIN G

PROJECT_TERMS: Adjuvant Chemotherapy;Adriamycin PFS;Affect;anti-PD-1;anti-PD-L1;anti-PD-L1 antibodies;anti-PD1 therapy;Antigens;Antineoplastic Agents;Bladder Neoplasm;bladder transitional cell carcinoma;Bladder Urothelium;Blood specimen;Cancer Patient;cancer therapy;Carboplatin;CD8-Positive T-Lymphocytes;Cells;Cessation of life;checkpoint inhibition;checkpoint therapy;chemotherapeutic agent;chemotherapy;Chemotherapy-Oncologic Procedure;Cisplatin;Clinical;Clonality;Combination Drug Therapy;Combination immunotherapy;cost;Cystectomy;Data;Disease;Dose;Equipoise;Fibroblasts;gemcitabine;Gene Expression Profile;genetic signature;Immune;immune cell infiltrate;immune checkpoint blockade;Immune checkpoint inhibitor;Immune response;Immunotherapy;improved;improved outcome;Individual;Laboratories;Level of Evidence;Malignant neoplasm of urinary bladder;Malignant Neoplasms;men;Methotrexate;Modality;molecular subtypes;mouse model;Muscle;muscle invasive bladder cancer;Neoadjuvant Therapy;neoantigens;novel;Patients;PD-1/PD-L1;PDL1 inhibitors;peripheral blood;permissiveness;phase II trial;Platinum;Progression-Free Survivals;Prospective cohort;Publishing;Randomized;randomized, clinical trials;Regimen;Resistance;response;Sampling;Schedule;Side;Specific qualifier value;Survival Rate;T cell response;T-Cell Receptor;Testing;TGFB1 gene;Therapeutic;transcriptomics;Transitional Cell Carcinoma;Treatment Protocols;tumor;tumor microenvironment;tumor-immune system interactions;United States;Urothelium;Vincristine

PROJECT_TITLE: Chemotherapy and the Bladder Cancer Immune Microenvironment


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Genetics;HIV/AIDS;Infectious Diseases;Lung;Lung Cancer;Precision Medicine;Prevention;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_DEPT: PSYCHIATRY

PHR: Smoking among PLWHA is a critical public health issue, with the rate of smoking 2-3 times greater than it is in the general population and the health risks of smoking outweighing those associated with the virus itself. Unfortunately, remarkably few studies have evaluated smoking cessation interventions for PLWHA and the available literature indicates that both behavioral and pharmacological smoking cessation interventions yield modest effect sizes and quit rates that are considerably lower than in the general population. A sizable literature, including studies by our research team, indicates that using the nicotine metabolite ratio (which represents the speed at which smokers metabolize nicotine; NMR) to personalize the selection of medications for tobacco use and the MAPS intervention to augment adherence to these medications can optimize treatments for tobacco use among PLWHA. As such, this trial will test these intervention optimization strategies to determine if individually or together these interventions can represent an effective approach to treating tobacco use in this population of smokers. As a major advance for this area of work, we will use rigorous methodology to evaluate these optimization strategies (i.e., a randomized design, biological verification, an ITT approach, and 6-month outcome assessments) and, overall, our approach is consistent with the MOST framework, which has been used to identify intervention components that maximize cessation outcomes. This trial will also assess theoretically derived and empirically based mechanisms through which these optimization strategies affect cessation and explore sub- groups who are more or less responsive to these strategies. In the end, this trial will determine if getting the right medication to the right person and helping to make sure they adequately use the medication optimizes tobacco cessation treatments among PLWHA in order to improve health outcomes for this population.

PI_NAMEs: GROSS, ROBERT ;SCHNOLL, ROBERT ADAM (contact)

PROGRAM_OFFICER_NAME: KAUFMAN, ANNETTE R

PROJECT_TERMS: Address;Adherence;Affect;Aftercare;Age;antiretroviral therapy;Area;Behavior Therapy;Behavioral;Biochemical;Biological;Budgets;Cardiovascular Diseases;CD4 Lymphocyte Count;Characteristics;Clinical Trials;Combined Modality Therapy;Control Groups;Counseling;Data;Dependence;design;Effectiveness;efficacious intervention;Evaluation;Evidence based intervention;Expectancy;follow-up;France;Gender;General Population;genetic variant;Health;Hepatitis C Therapy;HIV;HIV Infections;HIV/AIDS;improved;indexing;Individual;individualized medicine;Intervention;Life;Life Expectancy;Literature;Malignant Neoplasms;Mediating;Mediator;medication compliance;Mental Depression;Metabolism;Methodology;Modeling;modifiable risk;Motivation;multiphase optimization strategy;Nicotine;nicotine patch;nicotine replacement;nicotine use;novel;Outcome;Outcome Assessment;Participant;personalized approach;personalized medicine;Persons;Pharmaceutical Preparations;Pharmacogenetics;pharmacologic;Pharmacotherapy;placebo controlled trial;Population;Prevalence;Problem Solving;prospective;psychiatric comorbidity;Public Health;Race;Randomized;randomized, clinical trials;Reporting;Research;Risk;Risk Factors;Safety;Self Efficacy;Sex Orientation;side effect;Site;Smoke;Smoker;Smoking;smoking cessation;Smoking Cessation Intervention;Speed;standard care;Subgroup;substance use;systematic review;Testing;therapy adherence;Tobacco;tobacco abstinence;tobacco cessation intervention;Tobacco Dependence;Tobacco smoking behavior;Tobacco use;Tobacco Use Cessation;Toxic effect;Treatment Effectiveness;Treatment Efficacy;treatment optimization;Treatment outcome;treatment research;Underserved Population;varenicline;Variant;Virus;Work

PROJECT_TITLE: Testing Novel Pharmacogenetic and Adherence Optimization Treatments to Improve the Effectiveness of Smoking Cessation Treatments for Smokers with HIV


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

ORG_CITY: CAMDEN

ORG_NAME: CORIELL INSTITUTE FOR MEDICAL RESEARCH

ORG_STATE: NJ

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

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

PROGRAM_OFFICER_NAME: YASSIN, RIHAB R

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

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

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Cancer;Immunotherapy

ORG_CITY: CHAPEL HILL

ORG_DEPT: PHYSIOLOGY

PHR: PROJECT NARRATIVE T cells are a part of the immune system able to control tumor growth, but are ineffective in most cancer patients. Our lab has made the groundbreaking discovery that T cells entering tumors experience chronic stress that can exhaust T cell function in tumors. Our proposal will formally prove that targeting the chronic stress response holds the power to restore essential T cell functions and invigorate control of tumors to allow immunotherapy to work better in sarcomas with global implications for all cancer patients.

PI_NAMEs: THAXTON, JESSICA E (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: activating transcription factor 4;Acute;acute stress;Acute-Phase Reaction;Affect;Animals;anti-PD1 therapy;Apoptotic;arm;attenuation;biological adaptation to stress;cancer immunotherapy;Cancer Patient;CAR T cell therapy;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Death;Cell Death Induction;Cell Physiology;Cells;Cellular biology;Cessation of life;checkpoint therapy;Chronic;Chronic stress;Cytoprotection;Data;Development;drug development;effector T cell;Endoplasmic Reticulum;endoplasmic reticulum stress;Enzymes;Eukaryotic Initiation Factor-2;exhaust;exhaustion;Exhibits;experience;Generations;Genetic;Genetic Transcription;Human;humanized mouse;Immune system;immunogenic;Immunotherapy;Impairment;improved;in vivo;Inflammatory;innovation;interest;kinase inhibitor;Measures;Memory;Memory impairment;Metabolic;Metabolic Diseases;Metabolic dysfunction;metabolomics;Molecular;Molecular Target;mouse model;Mus;Mutant Strains Mice;overexpression;Oxidoreductase;Patients;PF4 Gene;Phase;Phenotype;Phosphorylation;Phosphotransferases;Process;programmed cell death protein 1;programs;Protein Kinase;protein kinase R;Proteins;Reactive Oxygen Species;Research;response;Role;Sarcoma;sensor;Shapes;Solid Neoplasm;Stress;success;T memory cell;T-Lymphocyte;targeted treatment;Testing;Toxic effect;trait;Translational Repression;Translations;tumor;Tumor Antigens;tumor growth;tumor microenvironment;Tumor Promotion;Tumor-Infiltrating Lymphocytes;Work

PROJECT_TITLE: Targeting Chronic ER Stress in T Cells to Improve Cancer Immunotherapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-M(08)F]


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Hearing impairment in children with autism spectrum disorders (ASDs) may contribute to core ASD symptoms by interfering with speech development and communication. Studies examining links between auditory system deficits and neurodevelopmental disorders are urgently needed for the advancement of new diagnostic methods and intervention strategies for these increasingly common disorders. With the application of novel mouse models of syndromic autism, this multidisciplinary project investigates how a gene linked to neuronal and immune dysfunction may lead to auditory system deficits, which in turn contribute to autism-like behaviors.

PI_NAMEs: COWAN, CHRISTOPHER W;LANG, HAINAN  (contact)

PROGRAM_OFFICER_NAME: CYR, JANET

PROJECT_TERMS: Abnormal Macrophage;Acoustic Nerve;Address;Adult;Animal Model;antagonist;Auditory;Auditory area;auditory processing;auditory stimulus;Auditory system;autism spectrum disorder;autism symptoms;autistic children;Behavior;behavior measurement;Biological Assay;Brain;C3AR1 gene;Cells;Characteristics;Chronic;Cochlea;Communication;Complement;Complement Factor H;Complement Inactivators;complement system;Data;Data Analyses;data integration;Development;Diagnostic Procedure;Disease;Electroencephalography;Enhancers;experimental study;factor A;Functional disorder;Functional impairment;G-Protein-Coupled Receptors;Gene Family;Genes;glial activation;hearing impairment;Human;human model;Hyperacusis;Image;Immune;Immune system;Immune System Diseases;Immunofluorescence Immunologic;individuals with autism spectrum disorder;Innate Immune System;interdisciplinary approach;Intervention;Investigation;Knowledge;Language Development;Lifestyle-related condition;Link;Macrophage;Macrophage Activation;Maintenance;Measurable;Microglia;Mitochondria;model of autism spectrum disorder;Modeling;Molecular;mouse model;multidisciplinary;multiple omics;Mus;Muscle Cells;Mutation;myocyte-specific enhancer-binding factor 2;neural;Neurodevelopmental Disorder;Neuroimmune;Neuronal Dysfunction;Neurons;Noise;novel;novel diagnostics;Pattern;Peripheral;Physiological;postnatal;programs;receptor;Regulation;Research;response;risk variant;Role;Social Behavior;Social Interaction;sound;Speech Development;spiral ganglion;Stress;Structure;Symptoms;Syndrome;Testing;Therapeutic;Time;transcription factor;treatment strategy;Wild Type Mouse;young adult

PROJECT_TITLE: Autism Spectrum Disorders and Auditory System Deficits: Role of Neuronal and Immune System Dysfunction

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICN-A (02)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Digestive Diseases;Genetics;Liver Cancer;Liver Disease;Orphan Drug;Rare Diseases

ORG_CITY: RICHMOND

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Hepatocellular carcinoma (HCC) is an extremely aggressive and invariably fatal cancer with no currently effective treatment for advanced disease. The proposal aims at analyzing the molecular mechanisms by which two interacting oncogenes, AEG-1 and MDA-9, cooperate to promote HCC, and evaluate combination of AEG-1 and MDA-9 inhibition as preventive and therapeutic approaches for HCC.

PI_NAMEs: FISHER, PAUL B;SARKAR, DEVANAND  (contact)

PROJECT_TERMS: advanced disease;angiogenesis;Animal Model;Astrocytes;Automobile Driving;BAY 54-9085;c-myc Genes;Cancer Etiology;Cell membrane;Cessation of life;Clinical;clinical application;Clinical Trials;combinatorial;Databases;Dependence;Development;Diethylnitrosamine;effective therapy;EGFR Protein Overexpression;Epidermal Growth Factor Receptor;Evaluation;expectation;FDA approved;Genes;Growth;Hepatocarcinogenesis;Hepatocyte;Human;Immunocompetent;In Vitro;in vivo Model;inhibitor;innovation;insight;Invaded;Investigational Therapies;Knock-out;Knockout Mice;Knowledge;liver cancer model;Malignant Epithelial Cell;Malignant Neoplasms;Mediating;Melanoma differentiation associated gene-9;Membrane;Methodology;Molecular;Monitor;mouse model;Mus;nano;nanoparticle delivery;Neoplasm Metastasis;novel;Nude Mice;Oncogenes;Oncogenic;overexpression;Pathogenesis;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phase I/II Clinical Trial;Phenotype;Play;Pre-Clinical Model;Preventive;Primary carcinoma of the liver cells;Property;Proteins;Protocols documentation;Research;RNA Interference Therapy;Role;Scaffolding Protein;Seminal;Signal Transduction;Small Interfering RNA;small molecule inhibitor;System;targeted treatment;Testing;The Cancer Genome Atlas;Therapeutic;Therapeutic Uses;therapeutically effective;trafficking;Transgenic Mice;Transgenic Organisms;Translations;Treatment Efficacy;tumorigenic;Unresectable;Work;Xenograft procedure

PROJECT_TITLE: Novel Targeted Combinatorial Therapy for Hepatocellular Carcinoma


ED_INST_TYPE: SCHOOLS OF NURSING

NIH_SPENDING_CATS: Cancer;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy

ORG_CITY: HOUSTON

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: Chemotherapy-induced neuropathy (CIN)—pain, numbness, and/or tingling distributed in the hands and feet— produces persistent symptoms affecting sensation and balance in cancer survivors. Up to 50% of cancer survivors still suffer from CIN 6 years after treatment, with a 1.8-fold increased risk of falls which negatively impacts quality of life. We propose to test auricular point acupressure (APA)—a non-invasive and nonpharmacological patient managed strategy—as an innovative solution for CIN.

PI_NAMEs: JOHNSON, CONSTANCE MARGARET (contact);LUKKAHATAI, NADA

PROGRAM_OFFICER_NAME: ALTSHULER, RACHEL DINA

PROJECT_TERMS: active method;Acupressure;Acupuncture Therapy;Adherence;Affect;afferent nerve;Aftercare;American Society of Clinical Oncology;Analgesics;Anti-Inflammatory Agents;Basal Ganglia;Biological Markers;Bortezomib;Brain;Cancer Patient;Cancer Survivor;cancer therapy;Cells;Characteristics;chemotherapy;chemotherapy induced neuropathy;China;Clinical;Clinical Trials;cognitive control;cytokine;Data;Demographic Factors;design;Dose;duloxetine;Ear;Ear Acupuncture;Ecological momentary assessment;effective therapy;efficacy evaluation;Equilibrium;Esthesia;Ethnic Origin;Europe;executive function;Exercise;expectation;experience;fall risk;Fatigue;Fingers;foot;functional disability;Functional disorder;Functional Magnetic Resonance Imaging;Gender;Goals;Hand;Health Care Costs;Image;improved;indexing;Inflammation;Inflammatory;innovation;Interferon Type II;Interleukin-1 beta;Interleukin-2;Interleukin-6;Intervention;Late Effects;Licensing;Macrophage;Malignant Neoplasms;Measures;Mediating;Monitor;morphine equivalent;Needles;neuroimaging;Neurons;Numbness;Opioid;opioid overuse;opioid use;Outcome;Pain;pain inhibition;Pain management;pain perception;pain relief;Pain Threshold;Participant;Patient Self-Report;Patients;Peripheral Nervous System;persistent symptom;Pharmaceutical Preparations;Physical Function;Placebo Effect;Placebos;Plasma;Platinum;primary endpoint;primary outcome;Provider;Psychophysics;Quality of life;Race;Randomized, Controlled Trials;Recommendation;Regulation;Reporting;Resources;secondary outcome;Self Management;Sensory;Sensory Thresholds;Severities;sex;side effect;Signal Transduction;skills;Sleep;smartphone application;Specificity;Stimulus;Survival Rate;Symptoms;Taiwan;taxane;Testing;Time;TNF gene;Toes;tool;treatment as usual;Vinca Alkaloids

PROJECT_TITLE: Auricular Point Acupressure to Manage Chemotherapy Induced Neuropathy

STUDY_SECTION: CMPC

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


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

ORG_CITY: PHILADELPHIA

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: We discovered that endorepellin, a soluble fragment of the heparan sulfate proteoglycan perlecan, evokes excessive autophagy or self-eating in the endothelial cells lining breast cancer vessels with no direct effects on the cancer cells. This novel bioactivity of endorepellin, via selective and specific targeting of the endothelia, will be investigated utilizing state-of-the-art molecular methodologies combined with highly-innovative mouse models of mammary carcinomas. Our research, by focusing on the tumor microenvironment and tumor secretome, will unravel unique avenues of study using endorepellin as a valuable treatment modality to combat this devastating disease in both primary and secondary malignancies.

PI_NAMEs: IOZZO, RENATO V. (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: adhesion receptor;Affect;Affinity;aggressive breast cancer;Allografting;angiogenesis;Angiogenesis Inhibitors;Angiogenic Factor;Angiostatic Proteins;antagonist;attenuation;Autophagocytosis;Binding;Biological;Biology;Breast Cancer cell line;Breast Carcinoma;C-terminal;Cancer Biology;cancer cell;cell behavior;Cells;cellular engineering;Cellular Stress;Chemicals;clinically relevant;combat;Communication;Complex;confocal imaging;Core Protein;Cues;Development;Disease;Eating;EIF-2alpha;Endothelial Cells;Endothelium;Enzymes;Exons;experimental study;Fibroblast Growth Factor Receptors;Funding;Gene Targeting;Genetic;genetic signature;Genetic Transcription;Grant;Growth;HAS2 gene;Heparan Sulfate Proteoglycan;Hyaluronan;Immunologics;In Vitro;in vivo;inducible Cre;inhibitor;innovation;Integrins;interdisciplinary approach;KDR gene;Knowledge;Laboratories;Ligation;Link;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Methodology;Modality;Modeling;Molecular;mouse model;mTOR inhibition;mTOR Inhibitor;Mus;mutant;Mutate;Names;nano-string;Neoplasm Metastasis;neoplastic cell;neovascularization;novel;novel therapeutics;Nutrient;nutrient deprivation;overexpression;Oxygen;paracrine;Parents;Parkin;Pathway interactions;perlecan;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphorylation Site;Phosphotransferases;predict clinical outcome;programs;promoter;Protein Tyrosine Phosphatase;Proteins;Proteoglycan;PTPN6 gene;receptor;Recombinants;Regulation;Research;Role;Second Primary Cancers;Sensitivity and Specificity;sensor;Signal Transduction;Specificity;Stromal Cells;Tamoxifen;Technology;Testing;Time;transcriptome;transcriptomics;Transgenic Mice;Translating;tumor;Tumor Angiogenesis;tumor microenvironment;tumor progression;tumorigenesis;tumorigenic;ultra high resolution;Vascular Endothelium;Vascularization;VEGFA gene;Women's mortality;Work;Zebrafish

PROJECT_TITLE: Proteoglycan regulation of tumor angiogenesis and endothelial cell autophagy

STUDY_SECTION: ICI

STUDY_SECTION_NAME: Intercellular Interactions Study Section[ICI]


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PUBLIC HEALTH RELEVANCE Colon cancer is a deadly cancer and new treatments are needed. Iron accumulation is an essential mechanism, which drives colon cancer progression. This grant will characterize mechanisms critical for iron- mediated growth, and identify new targets for the prevention and treatment of colon cancer.

PI_NAMEs: SHAH, YATRIK M (contact)

PROGRAM_OFFICER_NAME: LUO, RUIBAI

PROJECT_TERMS: addiction;aerobic glycolysis;antiporter;Apical;Area;Binding;Biomass;Bypass;cancer cell;Cancer Cell Growth;casein kinase;CDC2 gene;Cell Death;cell injury;Cell model;Cell Proliferation;Cells;Cellular Metabolic Process;Citric Acid Cycle;Colon;colon cancer progression;colon cancer treatment;colon carcinogenesis;Colon Carcinoma;Colonic Adenoma;Colonic Neoplasms;Colorectal Cancer;colorectal cancer risk;Critical Pathways;Cystine;Data;Deferoxamine;Development;Diet;dietary restriction;DNA Damage;Drug Targeting;Early Diagnosis;Embryo;epidemiologic data;Epithelium;Foundations;Generations;Genetic;Genetic Predisposition to Disease;Glutamates;glutathione peroxidase;Goals;Grant;Growth;Hepatic;hepcidin;Hormones;Human;Hydroxyl Radical;Incidence;Inflammatory;Intestines;Iron;Iron Chelating Agents;Iron Chelation;iron supplementation;JAK1 gene;Leucine Zippers;Lipid Peroxides;Liver;Malignant Neoplasms;Mediating;Metabolism;metal transporting protein 1;Micronutrients;Modeling;mouse model;Mucous Membrane;Mus;new therapeutic target;Normal Cell;novel;novel therapeutics;nuclear factor-erythroid 2;Nutritional Requirements;Oncogenic;Organoids;oxidative damage;p21 activated kinase;Pathogenesis;Pathway interactions;Patients;Phosphotransferases;Post-Translational Protein Processing;Prevention;Production;Proliferating;Protein Export Pathway;protein expression;Proteins;public health relevance;Radiosensitization;Reaction;Repression;Research;Resistance;resistance mechanism;Role;Signal Transduction;Site;SLC11A2 gene;STAT3 gene;Superoxides;System;targeted treatment;Testing;therapeutic target;Toxic effect;transcription factor;tumor;uptake;Work

PROJECT_TITLE: Understanding the mechanisms of iron addiction in colon cancer


ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE  The continuous proliferation of cancer cells demands profound translational and metabolic reprograming. Nevertheless, we still lack a clear picture of the unique adaptations that facilitate aberrant biomass accumulation specifically in cancer cells. This proposal seeks to understand the role of the transcription factor aryl hydrocarbon receptor (AHR) and its ligand kynurenine in protein synthesis and proliferation of colon cancer cells.

PI_NAMEs: CONACCI-SORRELL, MARALICE  (contact)

PROGRAM_OFFICER_NAME: WILLIS, KRISTINE AMALEE

PROJECT_TERMS: Amino Acids;Animals;APC gene;Aryl Hydrocarbon Receptor;Automobile Driving;Binding;Biogenesis;Biomass;cancer cell;Cancer Cell Growth;cancer therapy;cell growth;Cell Nucleus;Cell Proliferation;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Colon;Colon Carcinoma;colon growth;Development;Enzymes;Epithelial Cells;Gene Expression;Genes;Genetic;Genetic Transcription;Growth;Human;In Vitro;in vivo;inhibitor;knock-down;Knock-out;Kynurenine;Label;Ligands;macromolecule;Maintenance;Malignant Neoplasms;Manuscripts;Mediating;Metabolic;Metabolic Pathway;Modeling;Molecular;Monitor;Mus;MYC gene;novel;novel strategies;nutrient absorption;Oncogenes;Oncogenic;Organoids;Pathway interactions;Physiological;Play;Preparation;prevent;Production;Proliferating;Protein Biosynthesis;Proteins;Proto-Oncogene Proteins c-myc;Regulation;Research;Ribosomes;Role;Seminal;T-Lymphocyte;Testing;Therapeutic Intervention;transcription factor;Translations;Tryptophan;tumor;tumor growth;tumor metabolism;uptake

PROJECT_TITLE: The kynurenine-AHR pathway in biomass production


NIH_SPENDING_CATS: Biotechnology;Cancer;Digestive Diseases;Genetics;Immunotherapy;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Stomach Cancer

ORG_CITY: CORAL GABLES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

PHR: This study investigates how chronic stimulation by cytokines leads to inflammation and cancer in the stomach. The knowledge generated from this study will help design strategies to break the link between inflammation and cancer development as well as to block pro-tumor inflammatory signal while preserving the anti-tumor effectors for cancer prevention and treatment.

PI_NAMEs: CHEN, ZHIBIN  (contact)

PROJECT_TERMS: 3-Dimensional;Ablation;Adenocarcinoma;Adoptive Transfer;Affect;Age;Age Years;American;Animal Model;anti-CTLA4;Antibody Therapy;Atrophic Gastritis;Autoimmunity;Bone Marrow;cancer cell;cancer initiation;cancer prevention;cancer therapy;CD4 Positive T Lymphocytes;Cell Differentiation process;Cells;Chief Cell;Chimera organism;Chronic;connective tissue growth factor;CTLA4 blockade;CTLA4 gene;CTLA4 haploinsufficiency;cytokine;Cytokine Receptors;Data;design;Development;Disease;DNA Sequence Alteration;Dysplasia;Environmental Risk Factor;Epithelial Cells;Epithelium;Etiology;Exhibits;Gastric Adenocarcinoma;Gastric Metaplasia;gastric organoids;Gastritis;Genes;Genetic;Genetic Polymorphism;Genetic Predisposition to Disease;Genetic study;germ free condition;Goals;Growth Factor;Helicobacter pylori;heparin-binding EGF-like growth factor;Human;human model;IL13 gene;IL4 gene;Immune;Immunophenotyping;Inflammation;Inflammatory;insight;Integration Host Factors;Interleukin 4 Receptor;Interleukin-13;interleukin-13 receptor;knock-down;Knock-out;Knowledge;LGR5 gene;Link;Lymphoid Cell;Malignant - descriptor;Malignant Neoplasms;malignant stomach neoplasm;Mediating;Metaplasia;Modeling;Monoclonal Antibodies;Mucous Membrane;Mus;Neoplasms;neoplastic;Neoplastic Cell Transformation;Not Hispanic or Latino;novel;overexpression;Pathway interactions;Patients;Penetrance;Play;potential biomarker;Premalignant Cell;preneoplastic cell;preservation;Proliferating;Reporting;RNA Interference;Role;Signal Transduction;small hairpin RNA;spasmolytic polypeptide;stem cell expansion;stem cell population;stem cells;Stomach;Surveys;T-Lymphocyte;Testing;Th2 Cells;Tissues;transdifferentiation;Transgenes;Transgenic Organisms;trefoil factor;tumor;Tumor Immunity;tumorigenesis;White Women

PROJECT_TITLE: The role of type 2 inflammation in the initiation and progression of metaplastic differentiation and neoplastic transformation of gastric epithelia

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


NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Colorectal Cancer;Complementary and Integrative Health;Dietary Supplements;Digestive Diseases;Genetics;Inflammatory Bowel Disease;Natural Products;Nutrition;Prevention

ORG_CITY: COLUMBIA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA

PHR: NARRATIVE  The purpose of this project is to address the issue of alternative and impactful options for patients with Inflammatory Bowel Disease (IBD) to both treat their disease and prevent colon cancer that can result from long- standing and uncontrolled IBD. In comparing innovative treatment strategies, panaxynol (PA; isolated from American Ginseng) stands out as our most potent molecule tested; and we are exploring a unique mechanism that might not only elucidate colitis mechanisms and cures, but branch into other diseases driven by dysregulated mΦ function. The results of this project will lead to clinical trials and the standardization of PA as a stand-alone product, or as part of a synergistic combination therapy for patients with IBD.

PI_NAMEs: HOFSETH, LORNE J (contact);MURPHY, ELIZABETH ANGELA

PROGRAM_OFFICER_NAME: PERLOFF, MARJORIE

PROJECT_TERMS: Ablation;Address;Affect;American;Animal Model;Animals;anti-cancer;Anti-Inflammatory Agents;anticancer activity;Apoptosis;Area;Autoimmune Diseases;Biological Assay;Biomedical Engineering;cancer chemoprevention;cell type;Cells;cellular targeting;Chemicals;Chemoprevention;Chemopreventive Agent;Clinical;Clinical Trials;Coculture Techniques;Colitis;Colon;colon cancer prevention;colon cancer risk;Colon Carcinoma;Combined Modality Therapy;Complementary and alternative medicine;conditional knockout;conventional therapy;cost;Crohn's disease;Dangerousness;dextran sulfate sodium induced colitis;Disease;DNA;DNA Damage;Dose;Drug Kinetics;Economic Burden;Effectiveness;efficacy testing;Europe;experimental study;Exposure to;FDA approved;Fractionation;Functional disorder;Genetically Engineered Mouse;Genome;Ginseng Preparation;Goals;Immune;improved;in vivo;Induction of Apoptosis;Infiltration;Inflammatory;Inflammatory Bowel Diseases;innovation;Intestines;Knowledge;Lead;Life Style;LoxP-flanked allele;Macrophage;Malignant Neoplasms;Mediating;microbiota;Modeling;Molecular;murine colitis;Mus;Myeloid Cells;Natural Compound;Natural Source;Nature;North America;novel;p53 Signaling Pathway;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Plants;Prevalence;Property;replication stress;Research;response;Resveratrol;Sepsis;sex;side effect;Signal Pathway;Signal Transduction;single molecule;SIRT1 gene;small molecule;sound;Standardization;Testing;TNF gene;Toxic effect;TP53 gene;Treatment outcome;treatment strategy;Ulcerative Colitis

PROJECT_TITLE: Harnessing the power of p53 with Panaxynol from American Ginseng to suppress colitis and prevent colon cancer

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


ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Narrative This goal of this proposal is to determine how metabolically heterogeneous lung cancer cell sub-populations cooperate to drive invasion and metastasis. We will elucidate the molecular basis and mechanistic underpinnings of how differential metabolism maintains the distinct but cooperative biology that drives collective invasion and conceptually test if co-targeting different metabolic sub-populations limits metastasis.

PI_NAMEs: MARCUS, ADAM I.;SHANMUGAM, MALATHY (MALA)  (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: 3-Dimensional;Address;Area;Automobile Driving;Biology;cancer cell;Cell Proliferation;Cell Respiration;Cells;Chemicals;Citric Acid Cycle;Consumption;Data;Dependence;Environment;forging;Fostering;G6PD gene;Genetic;Genetic Transcription;genomic platform;Genomics;Glucose;Glucose Transporter;glucose uptake;Glycolysis;Goals;Heterogeneity;Hypermethylation;image guided;inorganic phosphate;Invaded;KRASG12D;Lead;Lung Adenocarcinoma;lung cancer cell;Maintenance;Malignant neoplasm of lung;Malignant Neoplasms;Metabolic;Metabolism;Modeling;Molecular;Molecular Analysis;Nature;Neoplasm Metastasis;neoplastic cell;Oxidative Phosphorylation;Pathway interactions;PDH kinase;Pentosephosphate Pathway;pharmacologic;Phenotype;Population;pressure;Proliferating;promoter;Publishing;Pyruvate;pyruvate dehydrogenase;Signal Pathway;SLC2A1 gene;spatiotemporal;targeted agent;targeted treatment;Technology;Testing;Therapeutic;tumor;Tumor Cell Invasion;tumor initiation;tumor progression

PROJECT_TITLE: Implications of metabolic heterogeneity on collective lung cancer cell invasion