NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Childhood Leukemia;Clinical Research;Gene Therapy;Genetics;Hematology;Immunotherapy;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Transplantation;Urologic Diseases

PHR: PROJECT NARRATIVE Acute myeloid leukemia (AML) is a deadly disease, especially for patients who have aggressive disease and who cannot receive a hematopoietic stem cell transplant (HCT). In a new Phase I/II clinical trial we propose to infuse patients who are not HCT candidates with genetically engineered T cells modified to selectively attack AML cells and prevent the disease from coming back. We also propose to perform the pre-clinical laboratory work for adding positive signals to the gene-edited cells to help them better attack the leukemia in future clinical trials.

PI_NAMEs: CHAPUIS, AUDE  (contact)

PROJECT_TERMS: Acute leukemia;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adoptive Transfer;Adult;adult leukemia;Affect;Affinity;Age;Allogenic;analytical method;Antigens;antileukemic activity;Autologous;Azacitidine;Back;Blood Platelets;Bypass;Categories;CD34 gene;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;cellular transduction;chemotherapy;Childhood Leukemia;Clinical;clinical efficacy;Clinical Trials;Clone Cells;cohort;comorbidity;conditioning;Consolidation Therapy;Cyclophosphamide;Cytogenetics;Data;design;Development;Disease;Disease remission;engineered T cells;Engineering;Epitopes;European;Failure;Flow Cytometry;fludarabine;Future;Gene Expression;Genes;Genitourinary system;Genomics;graft vs leukemia effect;Guidelines;Hematopoietic;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;high dimensionality;high risk;Immune response;Immunohistochemistry;In Vitro;in vivo;Infusion procedures;Laboratories;Lentivirus Vector;leukemia;leukemia relapse;leukemia treatment;Leukemic Cell;Leukocytes;Ligands;Measurable;Mediating;Memory;Morbidity - disease rate;Morphology;mortality;mouse model;Neoadjuvant Therapy;Nephroblastoma;neutrophil;Newly Diagnosed;next generation;Normal Cell;overexpression;patient tolerability;Patients;peripheral blood;Phase;Phase I/II Clinical Trial;Phase I/II Trial;Phenotype;Physiological;pre-clinical;preclinical efficacy;preclinical safety;prevent;Prevention;Probability;Proliferating;Publishing;receptor;Recommendation;Recovery;Regimen;Relapse;relapse risk;Research;Residual Neoplasm;response;Risk;Safety;SELL gene;Signal Transduction;single-cell RNA sequencing;standard of care;stem;stem cells;T cell response;T cell therapy;T memory cell;T-Cell Receptor;T-Lymphocyte;Tissues;Toxic effect;tumor;Tumor Antigens;Work

PROJECT_TITLE: Transgenic T cell Therapy for Acute Myeloid Leukemia


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Clinical Research;Hematology;Immunotherapy;Networking and Information Technology R&D (NITRD)

ORG_CITY: SEATTLE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE The activities of this Core involve collaboration with each Project and each Core in the design and biostatistical analysis of all studies support by this Program Project, including observational studies, pre-clinical studies, laboratory studies, and clinical trials. The Core also supports the collection of data from patients enrolled in the associated clinical trial, and makes these data and data required for observational studies available in a relational database.

PI_NAMEs: GOOLEY, TED  (contact)

PROJECT_TERMS: adult leukemia;Area;Biometry;Budgets;Clinical;Clinical Research;Clinical Trials;Code;Collaborations;computer cluster;Computer Systems;Data;Data Collection;data management;data repository;Databases;design;Electronics;Funding;Health Sciences;Housing;image archival system;Immunotherapy;immunotherapy clinical trials;Individual;Information Systems;Laboratories;Laboratory Research;Laboratory Study;Maintenance;Manuscripts;Monitor;Observational Study;operation;optical imaging;participant enrollment;Patients;Phase;preclinical study;Preparation;Process;programs;protocol development;Protocols documentation;Public Health;Quality Control;relational database;Reporting;Research;Research Design;Research Personnel;Research Project Grants;research study;Resources;Services;web-accessible;Work

PROJECT_TITLE: Core B: Biostatistics and Data Management

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RPRB-L (M1)]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Clinical Research;Data Science;Genetics;Hematology;Human Genome;Immunotherapy;Rare Diseases

PHR: Narrative Recent advances in single-cell genomic and high content spatial analysis technologies have shed new light on organ and tissue composition, delineating complex tissues and identifying new cell types. However, the data being generated by these approaches are becoming increasingly complex and difficult to fully analyze. The High Dimensional Cellular and Spatial Analysis Core (HDCSAC – Core C) will facilitate the efficient use of single-cell sequencing, high-dimensional tissue imaging, and support integrated high-dimensional data analysis for unbiased discovery and novel hypothesis generation.

PI_NAMEs: NEWELL, EVAN  (contact)

PROJECT_TERMS: Acute;Acute Myelocytic Leukemia;Adopted;adult leukemia;Antibodies;Antigens;Architecture;Biometry;Bone Marrow;Bone marrow biopsy;Bone Marrow Neoplasms;cell type;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Cluster Analysis;Complex;Data;data acquisition;Data Analyses;data management;Data Set;Development;engineered T cells;Engineering;experience;Flow Cytometry;Gene Expression Profile;Generations;Genomics;high dimensionality;Histopathology;Human;Immune;Immunity;Immunohistochemistry;In Situ;longitudinal analysis;Messenger RNA;Methods;multidimensional data;Multiple Myeloma;multiple omics;Mus;novel;Oligonucleotides;Organ;Patients;Population;programs;Protein Analysis;protein expression;Proteins;Research;Role;Sampling;Sequence Analysis;single cell analysis;single cell genomics;single cell sequencing;Specificity;Standardization;T cell clonality;T cell receptor repertoire sequencing;T cell therapy;T-Lymphocyte;Technology;Testing;Tissue imaging;Tissues;transcriptomics;treatment response;tumor;tumor microenvironment;Work

PROJECT_TITLE: Core C: High Dimensional Cellular and Spatial Analysis


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Health Services;Hematology;Immunotherapy;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

PHR: PROJECT NARRATIVE The Long-Term Follow-Up Unit (LTFU, Core D) supports the Program by providing extended data collection and biospecimen acquisition services to the Projects. Through a combination of chart review, annual surveys and active contact with participants and providers, Core D is responsible for ensuring that protocol requirements beyond the acute treatment phase (generally 2-3 months) are performed and research samples are collected. Core D also interacts closely with Core B, which is responsible for early data collection and all data analysis.

PI_NAMEs: LEE, STEPHANIE J (contact)

PROJECT_TERMS: Acute;Address;adult leukemia;Aftercare;Allogenic;Applications Grants;Area;biomedical referral center;cancer care;Cancer Center;Caring;Cell Therapy;Cellular immunotherapy;chronic graft versus host disease;Clinical;clinical care;Clinical Research;Core Grant;Data;Data Analyses;Data Collection;Database Management Systems;Databases;design;Documentation;Enrollment;Ensure;Evaluation;Event;follow-up;Functional disorder;genetically modified cells;Geography;Goals;Grant;Health;Hematopoietic Stem Cell Transplantation;Immunotherapy;Individual;Institution;instrument;Longterm Follow-up;Malignant Neoplasms;method development;Methods;Mind;Notification;Participant;Patients;Pediatric Hospitals;Phase;Physicians;prevent;Program Research Project Grants;programs;Prospective cohort;Protocols documentation;Provider;Recurrence;Relapse;relapse patients;Research;Research Methodology;Research Personnel;Research Project Grants;research study;Research Support;Resources;Risk Factors;sample collection;Sampling;Services;Specific qualifier value;Surveys;System;T cell therapy;T-Lymphocyte;Telemedicine;Time;Universities;Washington

PROJECT_TITLE: Core D: Long-Term Follow-Up


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Project narrative A subgroup of brain cancers known collectively as “gliomas” are the most common brain tumor of children and a major cause of cancer-related death in young adults. Conventional therapeutics for these cancers (surgery, chemotherapy, radiation) have significant side effects on growing children and fail completely on the most aggressive gliomas. The goal of this research program is to develop non-toxic (and curative) treatments for gliomas that arise in children and young adult with glioma by developing a new generation of medicines that specifically target tumors while sparing healthy cells.

PI_NAMEs: BATCHELOR, TRACY T (contact)

PROGRAM_OFFICER_NAME: HUBBARD, LEAH

PROJECT_TERMS: addiction;Address;Agreement;Amino Acid Substitution;Anabolism;antagonist;Award;Back;Basic Science;Biological Markers;Biological Products;Biometry;Boston;BRAF gene;Brain;Brain Neoplasms;cancer cell;Cancer Center;Cancer Etiology;cancer genomics;career;Cells;Cessation of life;chemotherapy;Child;Childhood;Clinical;clinical imaging;clinical material;Clinical Research;Clinical Trials;cohort;Combined Modality Therapy;computer science;CRISPR screen;Dana-Farber Cancer Institute;Data Set;Development;diffuse midline glioma;Disease;DNA Double Strand Break;DNA Repair Pathway;drug development;Drug Targeting;flexibility;Fostering;Friends;Funding;General Hospitals;Generations;Genetically Engineered Mouse;genome-wide;Glioma;Goals;Hospitals;Human;imaging study;inhibitor;Longterm Follow-up;Machine Learning;Magnetic Resonance Imaging;Malignant neoplasm of brain;Malignant Neoplasms;Massachusetts;medical schools;Medicine;Melanoma;Metabolic;Metabolism;Methods;Modality;Modeling;Molecular;mutant;Mutation;Oncogenes;Oncogenic;Oncoproteins;Operative Surgical Procedures;Parents;Pathology;Pathway interactions;patient response;Patients;Pediatric Hospitals;pediatric low grade glioma;Persons;Pharmaceutical Preparations;Phase;poly ADPR glycohydrolase inhib;prognostic indicator;programs;Progress Reports;Protein Kinase;Proteins;Protocols documentation;Publishing;Pyrimidine;Radiation;Recommendation;Recurrence;Refractory;repaired;Reproducibility;Research;Research Personnel;Research Project Grants;Resistance;response;satisfaction;Scientist;side effect;standard of care;structural biology;Subgroup;targeted treatment;Teaching Hospitals;temozolomide;Therapeutic;therapy development;tool;treatment strategy;tumor;United States Food and Drug Administration;Unresectable;Variant;Veins;Woman;Work;young adult

PROJECT_TITLE: Targeted Therapies for Glioma

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RPRB-M (M1)]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Orphan Drug;Rare Diseases

PHR: Project Narrative Primary brain tumors are the third leading cause of cancer-related death among all persons 15-39 years of age. In the fullness of time, the work that we propose with targeted therapies could change the standard of care and improve adult and pediatric patients with gliomas. The Administration Core serves as the "hub" for the governance of this SPORE research program.

PROJECT_TERMS: Administrator;Adult;Adult Glioma;Age Years;Award;Cancer Center;Cancer Etiology;Cessation of life;Childhood Glioma;Clinical Investigator;Clinical Trials;Collaborations;Communication;Communication Programs;design;Electronics;experience;Female;Foundations;Funding;Gender;Glioma;Grant;Human Resources;Image;improved;Individual;Infrastructure;Institution;Leadership;Malignant Neoplasms;Medicine;meetings;member;Minority;Monitor;multidisciplinary;pediatric patients;Persons;Positioning Attribute;Preparation;Primary Brain Neoplasms;programs;Protocols documentation;Research;Research Design;Research Personnel;Resources;Science;Series;Specialized Program of Research Excellence;standard of care;Structure;success;targeted treatment;Translational Research;Woman;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

PHR: Project Narrative Pediatric low-grade gliomas are the most common brain tumors of childhood and can cause devastating and life-long quality of life problems. In this study, we will combine advanced cancer cell analysis techniques and medical imaging-based artificial intelligence to improve targeted therapies, tumor monitoring, and prediction of recurrence in children with low-grade gliomas. The research will result in knowledge and tools that help us design better and safer therapies and determine how (and when) to best use those therapies in children with low-grade gliomas.

PI_NAMEs: KANN, BENJAMIN HARRIS (contact)

PROJECT_TERMS: Address;Advanced Malignant Neoplasm;Aftercare;Algorithms;Amino Acid Substitution;antagonist;Artificial Intelligence;artificial intelligence algorithm;automated algorithm;Award;Biochemical Pathway;Biological Products;BRAF gene;Brain;brain magnetic resonance imaging;cancer cell;career;chemotherapy;Child;Childhood Brain Neoplasm;Clinical;Clinical Data;clinical predictors;clinically relevant;Collaborations;Combined Modality Therapy;Curiosities;Data;Databases;deep learning;design;Development;dimer;Disease remission;Disease-Free Survival;Dose;efficacy evaluation;Event;Friends;Funding;Fusion Oncogene Proteins;Genetic;genomic profiling;Genomics;Glioma;Growth;Heterodimerization;Image;improved;inhibitor;inhibitor therapy;insight;Institution;Investigation;Knowledge;Link;longitudinal analysis;Magnetic Resonance Imaging;Mass Spectrum Analysis;Medical Imaging;MEKs;Melanoma;Monitor;Morbidity - disease rate;MRI Scans;multiple datasets;Mutation;Mutation Detection;Nevus;non-genetic;novel;Oncogenic;Oncoproteins;Operative Surgical Procedures;Parents;Patient Selection;Patients;pediatric low grade glioma;Periodicals;Pharmaceutical Preparations;Phase;Phase 0/1 Clinical Trial;phase II trial;precision medicine;prognostic technologies;programs;Progress Reports;Property;Protein Isoforms;Protein Kinase;Quality of life;Recombinants;reconstitution;Recurrence;repository;Research;Resected;response;Risk;satisfaction;side effect;Signal Transduction;single cell genomics;single-cell RNA sequencing;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Stable Disease;standard of care;success;survival prediction;targeted treatment;Techniques;Technology;Therapeutic;Time;tool;tumor;Variant;Wit;Work

PROJECT_TITLE: Project 1: Targeted therapeutics for pediatric low-grade glioma


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

PHR: Project Narrative Diffuse midline gliomas (DMG) are the most common malignant brain tumors of children. Radiotherapy is the only treatment known to prolong patient survival but DMGs inevitably recur following radiotherapy and are uniformly fatal. The goal of the work proposed here is to test a class of drugs that exploit a metabolic vulnerability of DMGs and have potential to greatly enhance the clinical outlook for children with these tumors. .

PI_NAMEs: HAAS-KOGAN, DAPHNE A. (contact)

PROJECT_TERMS: 3-Dimensional;addiction;Adult;Agar;Amino Acid Substitution;Anabolism;antagonist;Architecture;arm;Astrocytoma;authority;Biopsy;Biopsy Specimen;Boston;Brain;Brain Neoplasms;cancer cell;Cell Cycle Arrest;Cell Line;cell type;Cells;Child;Child Care;Childhood;Childhood Brain Neoplasm;Childhood Glioma;Clinical;clinical care;Clinical Trials;Collaborations;combinatorial;Combined Modality Therapy;Complement;Conduct Clinical Trials;CRISPR screen;Daphne plant;Dependence;design;diffuse midline glioma;Dihydroorotate dehydrogenase;DNA Double Strand Break;DNA Repair Pathway;DNA-Directed DNA Polymerase;Dose;drug action;drug development;Drug Targeting;druggable target;ds-DNA;Elements;Enzymes;experience;Freezing;Funding;Future;genome-wide;Glioma;Goals;Histone Deacetylase Inhibitor;Histone H3;Histones;Human;Imaging technology;Immunotherapy;innovation;Lead;Lysine;Malignant neoplasm of brain;Maps;mass spectrometric imaging;Metabolic;Methionine;Modality;Mus;mutant;Mutate;Myelogenous;neoplastic cell;neuro-oncology;Normal Cell;Nucleotides;Oncogenic;Oncoproteins;Pathology;Pathway interactions;Patients;Pediatric Hospitals;Penetrance;Pharmaceutical Preparations;Phase;phase 1 study;phase I trial;phase I/IIa trial;Phosphotransferases;Physicians;pre-clinical;Precision therapeutics;preclinical development;preclinical study;Progress Reports;Pyrimidine;Radiation therapy;Recommendation;Recurrence;reference genome;Refractory;Regimen;repaired;Research Personnel;Resistance;Sampling;Scientist;single cell genomics;skills;small molecule;Solid Neoplasm;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;standard of care;Stromal Cells;Sum;targeted treatment;Technology;Testing;Text;Therapeutic;therapeutic target;Time;Tissues;tool;transcriptomics;tripolyphosphate;tumor;tumor initiation;Tumor Tissue;Unresectable;Validation;validation studies;Visualization;Work;Xenograft Model;Xenograft procedure;young adult

PROJECT_TITLE: Project 2: Druggable dependencies in diffuse midline gliomas


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Neurosciences;Orphan Drug;Precision Medicine;Rare Diseases

PHR: PROJECT NARRATIVE Mutations in genes encoding isocitrate dehydrogenase (IDH) enzymes define subtypes of lower grade glioma in adults and can be targeted with mutant IDH inhibitor drugs, which delay the progression of these tumors. To combat resistance to mutant IDH inhibitor drugs, we propose to test two treatment strategies designed by our group to exploit vulnerabilities in glioma cells that are caused by IDH mutations. We will test these strategies in preclinical brain tumor models and in patients with IDH-mutant gliomas that do not respond to mutant IDH inhibitor drugs, thereby contributing to the development of new treatment options for this disease.

PI_NAMEs: MCBRAYER, SAMUEL KENT (contact)

PROJECT_TERMS: Address;Adult;Agar;alpha ketoglutarate;Basic Science;Binding;Biology;Brain Neoplasms;Cells;Chromatin;chromatin remodeling;Chromatin Structure;Clinical;Clinical Sciences;clinical translation;Clinical Trials;cohort;combat;Combined Modality Therapy;Correlative Study;demethylation;Dependence;design;Development;Diagnostic;Diffuse;Dihydroorotate dehydrogenase;Dioxygenases;Disease;DNA;DNA biosynthesis;Enzymes;Epigenetic Process;Exhibits;experience;Funding;gain of function mutation;Genes;Genetically Engineered Mouse;Glioblastoma;Glioma;Glycoside Hydrolases;Heterochromatin;Histones;Hypermethylation;Individual;individualized medicine;Indolent;inhibitor;inhibitor therapy;Isocitrate Dehydrogenase;Kinetics;Malignant - descriptor;Mediating;Metabolic;Metabolism;Modeling;Molecular;molecular marker;mutant;Mutation;Neurosphere;novel therapeutic intervention;nucleotide metabolism;Oncogenic;Oncoproteins;Organoids;patient population;Patients;Pharmaceutical Preparations;Phase;phase III trial;Poly Adenosine Diphosphate Ribose;pre-clinical;Progression-Free Survivals;Pyrimidine;Pyrimidine Nucleotides;Recurrence;replication stress;Repression;Resistance;restoration;Sampling;Signal Transduction;standard of care;synergism;targeted treatment;temozolomide;Testing;Therapeutic;Time;treatment strategy;tumor;tumor progression;Withdrawal;Work;young adult

PROJECT_TITLE: Project 3: Targeting IDH mutant gliomas


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

PHR: Core Narrative The goal of the Pathology Core is to provide expert pathology and biorepository services to the Projects. The Core will collect rare glioma tissue samples and clinical data from patients, create patient models, and apply innovative services to look at drug distribution in patient tumors to see if they respond to targeted therapies.

PI_NAMEs: LIGON, KEITH LLOYD (contact)

PROJECT_TERMS: Adult;Adult Glioma;Agar;Area;Award;biobank;Biological Assay;Biological Markers;blood-brain barrier penetration;BRAF gene;Brain;Cancer Center;cBioPortal;Cell Line;Cells;Childhood;Childhood Glioma;CLIA certified;Clinical;Clinical Data;Clinical Research;Clinical Trials;Collaborations;Collection;Consent;Core Biopsy;Data;data quality;data sharing;Dedications;deep learning;Diffuse;diffuse midline glioma;digital pathology;DNA Repair;drug distribution;Drug Targeting;Ensure;examination questions;Excision;experimental study;Fingerprint;Funding;Genetic Transcription;genomic data;Genomics;Glioma;Goals;Human;human tissue;Image;imaging modality;Imaging Techniques;Immune;Immunohistochemistry;improved;In Situ;inhibitor;innovation;innovative technologies;insight;Institution;interest;mass spectrometric imaging;Metabolic;Methods;Methylation;Midbrain structure;Modeling;molecular pathology;molecular targeted therapies;Multimodal Imaging;multimodality;multiplexed imaging;Mus;mutant;Mutation;neoplastic cell;neuropathology;Neurosphere;new technology;next generation sequencing;novel strategies;Organoids;Outcome;Pathologic;Pathologist;Pathology;pathology imaging;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phenotype;Play;preclinical trial;Process;programs;protein expression;Proteins;Reproducibility;Research;Research Project Grants;Resistance;Resources;response;response biomarker;RNA;Role;sample collection;Sampling;Services;Signal Pathway;single-cell RNA sequencing;SNP array;Specimen;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;standard of care;Standardization;targeted treatment;Technology;Testing;Therapeutic;therapeutic target;tissue resource;Tissue Sample;Tissues;Translational Research;tumor;United States National Institutes of Health;Validation;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Core 1: Pathology Core


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Data Science;Networking and Information Technology R&D (NITRD);Neurosciences;Orphan Drug;Rare Diseases

PHR: Core Narrative This Specialized Program of Research Excellence (SPORE) proposal is focused gliomas - a subtype of brain cancer that has heavy impact on life expectancy and quality of life children and young adults. Recent developments in statistical methodology for cancer research combined with access to low-cost, fast computing have resulted in higher standards in the definition of acceptable scientific evidence. Against this backdrop, the mission of this Biostatistics Core is to work scientists and clinicians on this SPORE ensure statistical integrity in the design of their experiments and enhance rigor and reproducibility in the interpretation of their data.

PI_NAMEs: LONDON, WENDY BETH (contact)

PROJECT_TERMS: Address;Animals;anti-cancer research;Bioinformatics;Biological Markers;Biostatistics Core;Calendar;Child;Clinical;Clinical Protocols;clinical trial analysis;Clinical Trials;Code;Collaborations;complex data;Computational Biology;Computing Methodologies;Consult;Consultations;cost;Data;Data Analyses;Data Collection;data exchange;data management;Data Science;Data Set;Databases;Dedications;design;Development;Ensure;Event;experimental study;Extramural Activities;Funding;Genomics;Glioma;Guidelines;Health protection;high standard;Human;Image;Investigation;Laboratories;Laboratory Study;Leadership;Life Expectancy;London;Malignant neoplasm of brain;Manuscripts;Measurement;Medical;member;metabolomics;Methodology;Methods;Mission;Modeling;Molecular;Monitor;novel;Outcome;Pathology;Patients;Peer Review;Preparation;Process;Proteomics;Publications;Quality of life;Reproducibility;Research;Research Design;Research Personnel;research study;Resources;Role;Safety;Scientist;Security;Specialized Program of Research Excellence;Statistical Data Interpretation;Statistical Methods;Statistical Models;symposium;targeted treatment;technical report;technical writing;Techniques;Time;Tissues;Translating;United States National Institutes of Health;Update;Variant;Work;Writing;young adult

PROJECT_TITLE: Core 2: Biostatistics Core


PHR: Project Narrative The Developmental Research Program supports innovative pilot studies that will generate feasibility data and that have the potential to emerge as full SPORE projects with possible future benefit for brain tumor patients.

PROJECT_TERMS: Award;Brain Neoplasms;Cancer Center;Communication;Data;Development;experience;Funding;Future;Glioma;Goals;Infrastructure;innovation;Institution;Measures;Monitor;Outcome;Patients;Pilot Projects;Process;Program Research Project Grants;programs;Progress Reports;Request for Proposals;Research;Research Project Grants;Scientist;synergism;targeted treatment;translational potential

PROJECT_TITLE: Developmental Research Program


PHR: Project Narrative The Career Enhancement Program provides research support for junior or new investigators in the field of glioma research. Through support, mentoring, and monitoring the program enables awardees to embark on successful careers in glioma research that will ultimately benefit patients.

PROJECT_TERMS: Adult;Award;career;Childhood;cohort;Dana-Farber Cancer Institute;experience;Faculty;faculty mentor;Funding;Glioma;Grant;Institution;interest;Measures;member;Mentored Clinical Scientist Development Program;Mentors;Minority;Monitor;multidisciplinary;neuro-oncology;Outcome;Patients;Phase;Process;Program Development;programs;Research;Research Personnel;Research Support;Resources;Source;success;System;Talents;targeted treatment;Teacher Professional Development;Training;Training Programs;translational scientist;Woman

PROJECT_TITLE: Career Enhancement Program


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

ORG_CITY: LA JOLLA

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative (Overall) Using powerful genetic, genomic, epigenomic and statistical techniques, we will support studies of the genetic basis of traits that have well-established relevance to substance use disorders. We expect that this National Center of Excellence will transform our understanding of substance use disorders and lead to the identification of specific genes, pathways and therapeutic targets. This center will enhance our understanding of genetic susceptibility to substance use disorders in humans and may identify new opportunities to treat psychiatric disorders including, but not necessarily limited to, substance use disorders.

PI_NAMEs: PALMER, ABRAHAM A (contact)

PROGRAM_OFFICER_NAME: LOSSIE, AMY C

PROJECT_TERMS: addiction;Address;Alcohols;Alleles;Attention;Behavior;Behavioral;Breeding;California;Cells;Cessation of life;Chromosomes;cocaine self-administration;Communities;comparison group;Complex;cost;Criminal Justice;Data;data management;data sharing;Databases;design;distributed data;Education;effective therapy;Electrophysiology (science);Epigenetic Process;epigenomics;Europe;FAIR principles;Funding;Gene Expression;Generations;Genes;Genetic;genetic approach;Genetic Predisposition to Disease;Genetic Recombination;Genetic study;Genetic Techniques;genome wide association study;Genomics;Genotype;Goals;Grant;Health Care Costs;Heroin;high school;Human;Impulsivity;Inbred Strains Rats;Individual Differences;innovation;Learning;Machine Learning;Maps;Measures;Mental disorders;Methodology;multidisciplinary;Mus;National Institute of Diabetes and Digestive and Kidney Diseases;National Institute of Drug Abuse;Newborn Infant;Nicotine;novel;Oxycodone;Pathway interactions;Phenotype;Pilot Projects;Population;premature;Productivity;Quantitative Genetics;Quantitative Trait Loci;rat genome;Rattus;Research Personnel;Scientist;Services;Slice;Substance Use Disorder;Techniques;therapeutic target;Time;trait;transcriptome;transcriptomics;undergraduate student;Universities;virtual;web site

PROJECT_TITLE: Center for Genetics, Genomics, and Epigenetics of Substance Use Disorders in Outbred Rats

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 SXC-E (M1)]


NIH_SPENDING_CATS: Brain Disorders;Drug Abuse (NIDA only);Genetics;Human Genome;Pediatric;Substance Misuse

PROJECT_TERMS: Accounting;addiction;Applications Grants;Behavioral;career;Characteristics;cloud based;Communities;conflict resolution;Data;Data Coordinating Center;data management;Databases;Development;Disputes;Ecosystem;Education;Ensure;Epigenetic Process;Event;experience;Feedback;Funding;Gender;Gene Expression;Genetic;genetic analysis;genetic pedigree;genome wide association study;Genomics;Genotype;Grant;high school;Human Genetics;human genomics;Human Resources;Hybrids;Institution;Journals;Link;Maps;Mediation;Medicine;meetings;member;Mission;National Institute of Drug Abuse;Neurosciences;Other Genetics;outreach;outreach program;pandemic disease;Persons;Phenotype;Pilot Projects;Preparation;programs;Progress Reports;prospective;Quantitative Trait Loci;Rattus;relational database;Research;Resources;Rodent;Role;Scientist;secondary analysis;Services;Students;Substance Use Disorder;success;summer program;undergraduate student;Update;verbal;web site;Work;Writing

PROJECT_TITLE: Core A


NIH_SPENDING_CATS: Brain Disorders;Cocaine;Drug Abuse (NIDA only);Genetics;Human Genome;Stimulant Use and Misuse;Substance Misuse

PI_NAMEs: SOLBERG WOODS, LEAH CATHERINE (contact)

PROJECT_TERMS: Academic Medical Centers;Address;Adoption;Alleles;Behavior;Breeding;Buffers;California;Chromosome Mapping;Chromosomes;Cocaine;Cocaine Dependence;cocaine exposure;Complement;cost;Data;Databases;Ear;Epigenetic Process;experience;Experimental Designs;Funding;General Population;Generations;Genetic;genetic predictors;Genetic Predisposition to Disease;genome wide association study;genomic locus;Genomics;Genotype;Germany;Goals;Grant;Haplotypes;Inbred Strains Rats;Individual;innovation;Institution;Italy;Laboratories;Lead;medical schools;Mission;Nature;Newborn Infant;Phenotype;Population;Predisposition;Price;Process;Qualifying;Rattus;Research Design;Research Personnel;Research Support;resilience;Resources;Sample Size;Sampling;Scientist;Self Administration;Services;Spain;Substance Use Disorder;Time;Tissues;trait;United States National Institutes of Health;Universities;Weaning;Work;young adult

PROJECT_TITLE: Core B


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Drug Abuse (NIDA only);Genetics;Human Genome;Substance Misuse

PROJECT_TERMS: Alleles;analysis pipeline;Award;Behavioral;behavioral phenotyping;Bioinformatics;bioinformatics pipeline;Brain region;Chromosomes;cost;Data;Databases;DNA;Dryness;Epigenetic Process;Funding;Gene Expression;Genes;Genetic;genetic analysis;genome sequencing;genome wide association study;Genomics;Genotype;Goals;Grant;Heritability;improved;Inbreeding;Individual;Libraries;Maps;Mitochondria;Mus;Output;Performance;phenome;Phenotype;phenotypic data;Polymorphic Microsatellite Marker;Population;Protocols documentation;Publications;Quantitative Trait Loci;Rattus;Reporting;Research Personnel;Resources;Services;SNP genotyping;Spleen;Sprague-Dawley Rats;Substance Use Disorder;Tail;Tandem Repeat Sequences;Time;Tissue Sample;Tissues;trait;transcriptome;transcriptome sequencing;Update;user-friendly;Variant;web site;whole genome;Y Chromosome;Zebrafish

PROJECT_TITLE: Core C


NIH_SPENDING_CATS: Brain Disorders;Drug Abuse (NIDA only);Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Substance Misuse

PI_NAMEs: POLESSKAYA, OKSANA O (contact)

PROJECT_TERMS: Alleles;Award;Bioinformatics;Budgets;Caenorhabditis elegans;career;Collaborations;Communities;Data;design;Disabled Persons;disadvantaged background;Discipline;Disparity population;effectiveness evaluation;Ensure;Epigenetic Process;Evaluation;experience;Feedback;follow-up;Funding;Future;Gender;Genes;Genetic;genome wide association study;genome-wide analysis;Genomics;Genotype;Goals;Grant;improved;Institution;Letters;machine learning method;Maintenance;mutant;pharmacologic;Phenotype;phenotypic data;Pilot Projects;Progress Reports;Publications;Rattus;Regulation;Research;Secure;Services;Substance Use Disorder;Time;trait;Underrepresented Minority;United States National Institutes of Health;Viral Vector;Wages;Work;Writing

PROJECT_TITLE: D


ADMINISTERING_IC: HS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

ORG_STATE: OH

PHR: PROJECT NARRATIVE The proposed study addresses a worldwide public health emergency, antimicrobial resistant bacterial infections and continued antibiotic effectiveness. This study disseminates a successful de-implementation strategy for excessive antibiotic use, a problem-solving strategy to facilitate integration of evidence-based guidelines to eliminate unnecessary post-operative antibiotic prophylaxis at 20 children’s hospitals. Results from this study will add to the evidence of the importance of facilitation as an important de-implementation strategy to eliminate low value and harmful healthcare practices.

PI_NAMEs: MCKAY, VIRGINIA R;NEWLAND, JASON  (contact)

PROGRAM_OFFICER_NAME: HENDERSON, SUSAN

PROJECT_TITLE: Dissemination of a Facilitation Strategy to Deimplement Unnecessary Post-Operative Antibiotics at Children's Hospitals

STUDY_SECTION: HSQR

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Genetics;Human Genome;Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: CHICAGO

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE This research aims to systematically investigate epigenomic regulation in the reward circuitry following cocaine self-administration, employing a range of single-cell multi-omics and spatial genomics methods. Additionally, by utilizing a diverse panel of mouse strains, the study aims to discern how various genetic backgrounds influence these molecular alterations, to shed light on the complex interplay between genetics and epigenetics in regulating gene expression that modulates cocaine self-administration behavior. The ultimate goal is to construct comprehensive gene regulatory networks that encapsulate this interplay, thereby advancing our understanding and providing avenues for targeted therapeutic strategies to combat cocaine addiction.

PI_NAMEs: ZHANG, ZHUZHU  (contact)

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Behavior;Behavioral;cell type;Cells;Chromatin;Cocaine;Cocaine Dependence;cocaine exposure;cocaine self-administration;cocaine use;Cocaine use disorder;combat;Complex;Computational Biology;Computer Analysis;Data;Dimensions;Dissection;DNA methylation profiling;Encapsulated;Epigenetic Process;epigenetic regulation;epigenetic variation;epigenome;epigenomics;Gene Expression;gene regulatory network;Genetic;Genomics;Goals;Hybrids;innovation;interdisciplinary approach;Methods;Molecular;mouse model;Mouse Strains;multiple omics;Mus;Neurobiology;Neuronal Plasticity;Neurosciences;Outcome;Pathway interactions;Play;Predisposition;Process;Public Health;Regulation;Regulatory Pathway;Research;Resistance;Resolution;response;reward circuitry;Role;Substance Use Disorder;System;targeted treatment;Therapeutic;Therapeutic Intervention;transcriptomics;Work

PROJECT_TITLE: The Genetic and Epigenetic Interplay of Cocaine Addiction: A Cell-Type, Circuitry, and Functional Dissection

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 IXR-N (M1)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

PHR: OVERALL PROGRAM NARRATIVE: Mucus-degrading intestinal bacteria and toxicities of hematopoietic cell transplantation  Some of the normal bacteria that live within our intestines can naturally break down mucus, which protects the lining of the intestinal tract. We have recently found that these bacteria play an important role in producing some of the most harmful toxicities that can affect patients undergoing a specialized medical treatment called allogeneic hematopoietic cell transplantation. We have assembled a team of physician- scientists and specialized experts on these specific bacteria to identify new ways to protect the intestinal mucus from these bacteria, with a goal of making allogeneic hematopoietic cell transplantation a safer procedure for patients.

PI_NAMEs: JENQ, ROBERT  (contact)

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: Ablation;Address;Affect;Allogenic;Antibiotic Therapy;Antibiotics;Applications Grants;Bacteria;Bacteroides;Behavior;Benign;Bifidobacterium;Biology;Biometry;Cells;Chloroplast DNA;Chronic Disease;Clinical;Collection;Colon;Communicable Diseases;Communities;Complex Mixtures;conditioning;Coupled;cytotoxic;Data;Data Collection;Databases;Diet;dietary;Dietary Fiber;Digestion;Disease;effective therapy;enteric pathogen;Enzymes;Epithelium;experimental study;fecal transplantation;Fermentation;Genetic;Genetic Heterogeneity;genetic manipulation;Glycoproteins;glycosylation;Goals;Goblet Cells;graft vs host disease;gut bacteria;gut microbiome;gut microbiota;Health;Health Benefit;Hematology;Hematopoietic;Hematopoietic Stem Cell Transplantation;Human;immunoregulation;improved;Individual;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Infusion procedures;Injury;Intervention Studies;Intestinal Diseases;Intestinal Graft Versus Host Disease;Intestines;Label;Libraries;Lower Gastrointestinal Tract;Malignant - descriptor;Malignant Neoplasms;Manuscripts;Martens;Medical;member;Meropenem;Metabolism;metagenomic sequencing;microbial;microbial community;microbiome;microbiota;microbiota transplantation;Minority;Modality;Modeling;Molecular Weight;Morbidity - disease rate;mortality;mouse model;Mucins;Mucolytics;Mucous body substance;Mus;Mutagenesis;mutant;natural hypothermia;Neutropenic Fever;novel;novel therapeutics;Nutrient;Pathway interactions;Patients;Physicians;Play;Polysaccharides;pre-clinical;Pre-Clinical Model;Predisposition;preservation;prevent;Preventive;procedure safety;Program Research Project Grants;programs;Property;Prospective Studies;Publications;remediation;Reproducibility of Results;Resources;Role;sample collection;Scientist;Services;Testing;Therapeutic;Tissues;tool;Toxic effect;translational approach;Transplant Recipients;uptake;Visualization;Volatile Fatty Acids

STUDY_SECTION: HLBP

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP (MA)]


NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;Immunotherapy;Prevention;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

PROJECT_TERMS: Academic Medical Centers;Applications Grants;Bacteria;Bacteriophages;Bacteroides;Biometry;Biostatistics Core;Cancer Center;capsule;Cell Wall;Clinical;Clinical Data;Colon;Communication;Communication Programs;conditioning;Data Analyses;Data Collection;data sharing;Diet;Dietary Fiber;Ecology;Ensure;Evaluation;experimental study;Fever;Foundations;Funding;Gene Expression;Goals;Hematopoietic Stem Cell Transplantation;Heterogeneity;Human;Human Resources;improved;In Vitro;in vivo;Individual;Intervention Studies;Intestinal Graft Versus Host Disease;Intestines;Leadership;Link;longitudinal analysis;meetings;mouse model;Mucins;Mucous body substance;Mus;National Heart, Lung, and Blood Institute;novel strategies;novel therapeutics;organizational structure;Patients;prevent;Program Research Project Grants;programs;Research Personnel;Role;Services;Standardization;success;synergism;Technology;Testing;Therapeutic;Time;Toxic effect

PROJECT_TITLE: Administrative, biospecimen and biostatistical core


NIH_SPENDING_CATS: Biotechnology;Genetics;Immunotherapy;Microbiome;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

PI_NAMEs: DAVEY, LAUREN ELIZABETH (contact)

PROJECT_TERMS: Anaerobic Bacteria;Bacteria;Bacteroides;Bioinformatics;Cells;Colon;Communities;comparative genomics;Complex;Coupled;Data;Data Analyses;Databases;Degradation Pathway;Development;dietary;Engineering;Enzymes;experience;Flow Cytometry;gene function;Genes;Genetic;Genetic Engineering;genetic manipulation;Genetic Screening;gut microbiome;gut microbiota;Hematopoietic Stem Cell Transplantation;High-Throughput DNA Sequencing;host-microbe interactions;Human;In Vitro;Individual;interest;Intestines;Label;Libraries;Link;Martens;metagenomic sequencing;Methods;Microscopy;Mucins;Mucous body substance;Mutagenesis;mutant;Neutropenic Fever;Pathway interactions;Patient Isolation;Patient-Focused Outcomes;Patients;Polysaccharides;poor health outcome;Predictive Factor;programs;protein expression;Reagent;Recombinant Proteins;Regulation;Research;Resources;Services;Techniques;Testing;tool;Toxic effect;transposon sequencing;uptake;Visualization

PROJECT_TITLE: Genetics Core for Mucin Degrading Bacteria


NIH_SPENDING_CATS: Digestive Diseases;Hematology;Immunotherapy;Microbiome;Nutrition;Orphan Drug;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

PROJECT_TERMS: Address;Allogenic;Antibiotic Therapy;Antibiotics;Bacteria;Bacterial Genes;Bacterial Translocation;Bacteroides;Bacteroides thetaiotaomicron;Behavior;Benign;Biology;Body Weight decreased;Caloric Restriction;Cells;Chemicals;chemotherapy;Clinical;Colon;Colonic inflammation;commensal bacteria;Communities;conditioning;Data;Development;Diet;disorder risk;effective therapy;efficacy evaluation;Enzymes;experience;experimental study;fecal transplantation;Feces;Fever;Fiber;Gene Expression;Genetic;Genetic Transcription;graft vs host disease;gut microbes;gut microbiota;Hematological Disease;Hematopoietic Stem Cell Transplantation;high risk;Immune;improved;In Vitro;in vivo;Individual;induced hypothermia;Infection;Inflammatory;inhibitor;Injury;insight;Intervention Studies;Intestinal Graft Versus Host Disease;Intestines;Knowledge;Learning;Life;Link;Lower Gastrointestinal Tract;Malignant - descriptor;Mediating;Melphalan;member;Meropenem;microbiota;Modality;Monosaccharides;Morbidity - disease rate;mortality;mouse model;Mucins;Mucolytics;Mucous body substance;Mus;Naphthoquinones;natural hypothermia;Neutropenic Fever;novel;Oral;Oral Administration;Patients;Plants;Polysaccharides;preservation;Propionates;Prospective Studies;Publishing;Radiation therapy;remediation;Reporting;Reproducibility of Results;Risk;Source;synergism;Thinness;Toxic effect;translational approach;Transplant Recipients;treatment risk;Up-Regulation;Work;Xylose

PROJECT_TITLE: Mucin preserving strategies to reduce allo HCT toxicities


NIH_SPENDING_CATS: Digestive Diseases;Genetics;Hematology;Immunotherapy;Microbiome;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

PI_NAMEs: VALDIVIA, RAPHAEL H (contact)

PROJECT_TERMS: Adherence;Allogenic;Bacteria;Bacteriophages;Biological Response Modifiers;capsule;Cell Transplantation;Cells;Collection;Colon;commensal bacteria;Complex;conditioning;Consumption;Data;Development;Disease;disease model;Distal;Ecology;Enzymes;Epigenetic Process;epigenetic variation;Epithelial Cells;Epithelium;experimental study;Fever;Gastrointestinal tract structure;Genetic;Genetic Transcription;Genetic Variation;genomic variation;Genomics;Goblet Cells;graft vs host disease;Growth;gut colonization;gut microbiota;Health;Hematopoietic;Hematopoietic Stem Cell Transplantation;Human;human model;Hydrolase;Immune;Immune signaling;Immunologic Stimulation;immunoregulation;In Vitro;Individual;intestinal epithelium;Intestinal Graft Versus Host Disease;Intestines;Link;Mediating;Metagenomics;metatranscriptomics;Microbe;microbial;microbiota;mouse model;Mucins;Mucolytics;Mucous body substance;Mucous Membrane;Mus;Mutagenesis;mutant;Neutropenic Fever;Organoids;Patients;Polysaccharides;Pre-Clinical Model;Predisposition;Property;reconstitution;Regulation;response;Risk;Risk Reduction;Severities;Severity of illness;Signal Induction;Signal Pathway;Site;stool sample;Surface;System;Testing;Therapeutic;Thinness;Toxic effect;Transplantation Conditioning

PROJECT_TITLE: Akkermansia muciniphila mucolytic and immunomodulatory properties and intestinal GVHD


NIH_SPENDING_CATS: Dietary Supplements;Digestive Diseases;Genetics;Hematology;Immunotherapy;Microbiome;Nutrition;Prevention;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

PI_NAMEs: MARTENS, ERIC C (contact)

PROJECT_TERMS: Affect;Allogeneic Bone Marrow Transplantation;Allogenic;Animal Model;Bacteria;Bacteroides;Bacteroides thetaiotaomicron;Behavior;cancer therapy;Carbohydrates;Categories;Colon;Communities;Complex Mixtures;Consumption;Development;Diet;Diet and Nutrition;dietary;Dietary Carbohydrates;Dietary Fiber;Digestion;Disease;Disease Outcome;Distal;Eating;Edible Plants;enteric pathogen;Enzymes;Epithelium;Experimental Genetics;experimental study;Fermentation;Fiber;Food;Fruit;fruits and vegetables;gene repression;General Practitioners;Genes;Genetic Transcription;Germ-Free;Glycoproteins;Gnotobiotic;Goals;Goblet Cells;Grain;Graph;Growth;gut bacteria;gut microbiome;gut microbiota;Health;Health Benefit;Hematopoietic Stem Cell Transplantation;Human;ileum;improved;In Vitro;in vivo;Inflammatory Bowel Diseases;inflammatory marker;innovation;Intestinal Diseases;Intestines;Investigation;Knowledge;Measurement;Measures;Mediating;member;Metabolic;Metabolism;microbial;microbial community;microbiome;microbiome components;microbiome therapeutics;microbiota;microorganism;Modeling;Molecular;Molecular Genetics;molecular marker;Molecular Weight;Mucins;Mucous body substance;Mus;mutant;novel therapeutics;Nutrient;Nuts;Organism;Output;Patients;Pentosephosphate Pathway;Physiology;Plants;Play;Polysaccharides;Predisposition;Prevalence;Prevention;Regulation;Regulatory Pathway;Repression;response;Role;Sampling;Severity of illness;Source;sugar;Symptoms;Testing;Thick;Toxic effect;transcription factor;Translating;transplant model;Transplant Recipients;Transplantation;Vegetables;Volatile Fatty Acids

PROJECT_TITLE: Dietary fiber, mucin-degrading Bacteroides, and intestinal GVHD


ORG_CITY: NEW YORK

ORG_DEPT: PHYSIOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Narrative Work from our group suggests that functional declines in aging blood-forming hematopoietic stem cells (HSC) that affect their epigenetic status and signals from the aging niche that alter the transcriptional milieu or promote expansion of HSC compartments have an impactful role in myeloid disease progression by promoting clonal expansion of mutated (pre-leukemic) HSCs and emergence of Acute Myeloid Leukemia (AML). The goal of our program is to apply cutting edge genetic tools and single cell technology to integrate studies of clonal mutational evolution and niche components in patients and mouse models, to establish the mechanisms through which the aging marrow supports the outgrowth of AML initiating clones.

PI_NAMEs: KOUSTENI, STAVROULA  (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Acute Myelocytic Leukemia;Address;Affect;age related;Aging;aging mechanism;aging related;beta catenin;Biometry;Blood;Bone Marrow;Cell Compartmentation;cell stroma;Cells;Cellular biology;Clinical;Clinical Data;clinical translation;Clonal Expansion;Clonal Hematopoietic Stem Cell;cohort;cytotoxic;Data;Data Analyses;data integration;data sharing;Development;Disease;Disease Progression;Dysmyelopoietic Syndromes;Elderly;Emergency Situation;Environment;Epigenetic Process;Event;Evolution;fitness;functional decline;Gene Expression Profile;Genetic;Genetic Drift;Genetic Transcription;Goals;Hematopoiesis;hematopoietic stem cell aging;hematopoietic stem cell expansion;Hematopoietic stem cells;Heterogeneity;high risk;Human;human data;Inflammation;Inflammatory;Interleukin-1;Intervention;Leukemic Hematopoietic Stem Cell;leukemic transformation;Link;Maps;Marrow;Mediating;Modeling;Molecular;Molecular Profiling;mouse model;mRNA Stability;multidisciplinary;Mus;Mutate;Mutation;Myelodysplastic/Myeloproliferative Disease;Myelopoiesis;Myeloproliferative disease;novel;Pathway interactions;Patients;Population;Preleukemia;pressure;Process;programs;Reagent;regenerative;Research Personnel;Role;sample collection;Sampling;Signal Transduction;single cell analysis;single cell genomics;single cell technology;Speed;stem cell population;stem cells;Stress;Stromal Cells;Systems Biology;Therapeutic Intervention;Time;tool;TP53 gene;transcriptomics;Work

PROJECT_TITLE: Aging-related hematopoietic stem cell intrinsic and microenvironmental signals in AML transformation


NIH_SPENDING_CATS: Aging;Biotechnology;Cancer;Clinical Research;Genetics;Hematology;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

PHR: Narrative The objective of the Administrative Core is 3-fold: 1) to foster and facilitate overall progress of the scientific work of the Program foster, scientific focus, integrity and ethical conduct and support to the Projects and Core B; 2) to provide fundamental services and capabilities related to AML patient samples and samples from healthy aging individuals and support for xenograft organoid models; and 3) to provide biostatistical support.

PROJECT_TERMS: Address;Age;age related;Aging;aging related;Aliquot;Arthroscopy;Authorization documentation;Biometry;Biopsy;bone;Bone Marrow;Cells;Classification;Clinical;Clinical Data;Clinical Research;clinical translation;Clonal Evolution;Collection;Comprehensive Cancer Center;Confidentiality of Patient Information;Cryopreservation;Cryopreserved Cell;Data;data access;Data Analyses;data sharing;Databases;DNA Library;Ethics;Experimental Designs;experimental study;Fostering;Gene Frequency;Genes;genetic variant;healthy aging;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Herbert Irving Comprehensive Cancer Center;Hip region structure;hip replacement arthroplasty;Human;Human Resources;in vivo;Individual;Institution;Laboratory Study;Leadership;Link;Maps;Medical center;meeting reports;meetings;member;Modeling;Molecular;mouse model;Mus;Mutate;Mutation;Myeloproliferative disease;Organoids;Patients;Plasma;Population;Prevalence;Program Research Project Grants;programs;Progress Reports;Publications;Recombinant DNA;Records;Reporting;Research;Research Personnel;Sampling;Schedule;Series;Services;Signal Transduction;sound;Source;Statistical Methods;stem cells;targeted sequencing;Tissue Banks;Tissue Sample;tool;transcriptomics;translational study;Travel;Universities;Vertebrates;web page;web site;Work;Writing;Xenograft procedure

PROJECT_TITLE: Core A: Administrative Core


NIH_SPENDING_CATS: Aging;Cancer;Childhood Leukemia;Clinical Research;Genetics;Hematology;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

PHR: PROJECT NARRATIVE  In addition to genetic driver mutations, activation of emergency myelopoiesis (EM) pathways contributes to leukemia development. However, our understanding of the role of EM pathway engagement in leukemia is still incomplete, which represents a major roadblock in the translation of our extensive knowledge of this fundamental process of demand-adapted myeloid cell amplification into treatments for acute myeloid leukemia (AML) patients. The overall goal of this project is to identify key regulatory nodes that could be exploited to disrupt EM pathway activation and prevent leukemia progression.

PI_NAMEs: PASSEGUE, EMMANUELLE  (contact)

PROJECT_TERMS: Acceleration;Acute;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;Affect;age related;Aging;aging related;Architecture;Atlases;Automobile Driving;Blood;Bone Marrow;cell behavior;Cells;Chronic;clinical translation;Clonal Evolution;Clonal Expansion;Consensus;CRISPR/Cas technology;Cytometry;Cytotoxic agent;Development;Disease;Disease Progression;DNA Methylation;DNMT3a;DNMT3a mutation;driver mutation;Dysmyelopoietic Syndromes;Elderly;Elements;Emergency Situation;Environment;Epigenetic Process;epigenetic regulation;Exposure to;FLT3 gene;Fluorouracil;Genetic;Genetic Transcription;Goals;granulocyte;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Hematopoietic System;high risk;Homeostasis;Human;humanized mouse;Image;in vivo;Individual;Infection;Inflammatory;Injections;Interleukin-1;Investigation;Knowledge;Lead;leukemia;Leukemic Hematopoietic Stem Cell;leukemic stem cell;leukemic transformation;leukemogenesis;Link;Macrophage;Malignant - descriptor;Modality;Modeling;mouse model;Multipotent Stem Cells;Mus;Mutation;Mycobacterium avium;Myelodysplastic/Myeloproliferative Disease;Myelogenous;Myeloid Cells;Myelopoiesis;Natural regeneration;older patient;Organism;Pathogenesis;Pathway interactions;Patients;Population;pre-clinical;Preleukemia;prevent;Process;Production;progenitor;programs;Proliferating;Recording of previous events;regenerative;Regulation;response;Risk Factors;Role;screening;self-renewal;Signal Transduction;single-cell RNA sequencing;Somatic Mutation;Stimulus;Stress;Structure;success;System;Systems Biology;Testing;therapeutic target;tissue mapping;Transcriptional Regulation;transcriptomics;translational study;Translations;Work

PROJECT_TITLE: Project 1: Role of emergency myelopoiesis as a driver of clonal evolution in AML


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

PHR: Project 2: Microenvironmental and inflammatory mechanisms in MDM4-driven AML pathogenesis. Project Leader: Ulrich Steidl Project Narrative We hypothesize that MDM4 overexpression acts in ARCH/MDS-to-AML progression in the context of microenvironmental changes and selection pressures that are frequently encountered during aging and inflammatory stress. Our studies will provide novel mechanistic insights into combinatorial cell-intrinsic/extrinsic preleukemic to AML progression as well as a preclinical proof- of-concept for the design of preventative clinical trials in the future.

PI_NAMEs: STEIDL, ULRICH  (contact)

PROJECT_TERMS: Address;age related;Aging;aging related;Automobile Driving;beta catenin;Biological Assay;cancer cell;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Cessation of life;Clinical;Clinical Trials;Clone Cells;Collaborations;combinatorial;cytokine;Data;design;Disease;Double Minutes;Epigenetic Process;Felis catus;Future;Genetic;Genetic Transcription;genomic biomarker;Hematopoiesis;Hematopoietic stem cells;high risk;Human;improved;In Vitro;in vivo;Inflammatory;inhibitor;insight;Interleukin-1;leukemia;Leukemic Cell;Leukemic Hematopoietic Stem Cell;leukemic stem cell;leukemic transformation;Linear Models;Maps;Mediating;Modeling;Molecular;mouse model;Mus;Mutation;novel;novel strategies;Outcome;overexpression;Pathogenesis;Pathway interactions;Patients;pharmacologic;Phenotype;pre-clinical;Preleukemia;pressure;prevent;Preventive treatment;Process;Publishing;Relapse;Reporting;Role;Sampling;Science;Signal Pathway;Signal Transduction;stem cells;Stress;Testing;Therapeutic Intervention;therapeutically effective;TP53 gene;tumor heterogeneity;tumor progression


NIH_SPENDING_CATS: Aging;Cancer;Clinical Research;Genetics;Hematology;Prevention;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

PHR: PROJECT 3 NARRATIVE We have identified a stroma cell-triggered transcriptional event driving MDS to AML transformation. We will delineate the mechanism of this pathway in AML evolution and clonal dynamics. These studies will identify transcriptional and clonal events that are significant contributors to AML transformation, define the role of the stroma in their regulation and can lead to new therapeutic approaches that target stroma-elicited signals to prevent or treat AML.

PROJECT_TERMS: Abnormal Karyotype;Age Factors;age related;Aging;aging related;Agreement;Automobile Driving;beta catenin;Bone Marrow;Cell Count;cell stroma;Cells;Chronic;clinically relevant;Clonal Evolution;Clonal Expansion;cohort;Cytogenetics;Databases;Development;Disease;Disease remission;Dysmyelopoietic Syndromes;Early identification;effective therapy;Emergency Situation;Epigenetic Process;Event;Evolution;founder mutation;Genes;Genetic;Genetic Transcription;Genetically Engineered Mouse;Hematology;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Heterogeneity;Human;human stem cells;Inflammation;Inflammatory;Inhibition of Apoptosis;insight;Interleukin-1;Intrinsic factor;Lead;Leukemic Cell;Leukemic Hematopoietic Stem Cell;Maintenance;Malignant - descriptor;Maps;Marrow;Mediating;Megakaryocytes;Messenger RNA;Modeling;Morphology;mouse model;Mus;Mutation;Myelogenous;Myeloid Progenitor Cells;Myelopoiesis;Myeloproliferative disease;novel therapeutic intervention;Osteoblasts;overexpression;Pathogenesis;Pathway interactions;Patients;permissiveness;Play;Population;Precancerous Conditions;Preleukemia;prevent;Preventive;progenitor;Regenerative response;Regulation;Resistance;Risk;Role;Sampling;Secondary to;Signal Transduction;single-cell RNA sequencing;Somatic Mutation;stem cell population;Stress;Stromal Cells;targeted treatment;The Cancer Genome Atlas;therapeutic target;therapy development;Transplantation

PROJECT_TITLE: Project 3: Role of stromal cell-activated CNOT6L deadenylase in driving AML transformation


NIH_SPENDING_CATS: Aging;Bioengineering;Biotechnology;Cancer;Cancer Genomics;Data Science;Genetics;Human Genome;Networking and Information Technology R&D (NITRD);Stem Cell Research;Stem Cell Research - Nonembryonic - Human

PHR: Core B: NARRATIVE The Computational Genomics Core will provide a centralized structure to collect, analyze and integrate data from all three projects. Simultaneous genomic, transcriptomic and proteomic mapping of bone marrow (BM) tissue will provide a unique opportunity to visualize the numerous cell types, their states and pathway specific expression patterns in a spatially resolved manner. The generated datasets will be mined to chart the rewiring of both cell states in the BM niche and their aberrant signaling during AML transformation. The Core will apply methods for processing and analysis of single-cell RNA sequencing data, inference and visualization of AML clonal evolution, reconstruction of transcriptional regulatory networks and analysis of transcriptional targets, and integration of data across technologies.

PI_NAMEs: RABADAN, RAUL  (contact)

PROJECT_TERMS: 3-Dimensional;aging related;analysis pipeline;Antibodies;Automobile Driving;Bayesian Network;blind;bone;Bone Marrow;Cell Communication;cell type;Cells;Chromatin;Clonal Evolution;Collaborations;computational pipelines;Computational Technique;computer science;Computing Methodologies;Cytometry;Data;Data Analyses;data integration;Data Set;Development;DNA analysis;DNA Sequence Alteration;DNA sequencing;Epigenetic Process;Evolution;experimental study;Gene Expression;gene regulatory network;Genes;Genetic;Genetic Transcription;genomic data;Genomics;Genotype;Goals;Hematopoietic stem cells;Image;image registration;improved;In Situ;Inflammatory;intercellular communication;leukemogenesis;Machine Learning;Malignant Neoplasms;Maps;Marrow;Mathematics;Methods;Methylation;multimodality;Multiomic Data;Mutation;Neighborhoods;novel;Pathway interactions;Pattern;Physics;Population;Preleukemia;Proteomics;reconstruction;Research Personnel;Scientist;segmentation algorithm;Signal Transduction;single cell analysis;single-cell RNA sequencing;skeletal;Source;statistics;Stromal Cells;Structure;Techniques;Technology;Testing;Tissues;tool;Training;transcription factor;transcription regulatory network;transcriptome;transcriptomic profiling;transcriptomics;Variant;Visualization;Work

PROJECT_TITLE: Core B: Computational Genomics Core


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Social Determinants of Health

ORG_CITY: GLASSBORO

ORG_DEPT: BIOLOGY

ORG_NAME: ROWAN UNIVERSITY

ORG_STATE: NJ

PHR: The Cumberland Bridge to Rowan (CB2) Bridges to the Baccalaureate Research Training Program is a biomedical research training program seeking to diversify the biomedical workforce. Trainees in the program will develop scientific and research skills that will support discovery in biomedical sciences which ultimately support public health.

PI_NAMEs: KRUFKA, ALISON  (contact);KRUMMENACHER, CLAUDE F;RANDA, MARK

PROGRAM_OFFICER_NAME: NELSON, SHAKIRA M

PROJECT_TERMS: Area;Articulation;Associate Degree;Bachelor's Degree;Bioinformatics;Biomedical Research;bridge to the baccalaureate;career;college;community college;County;Creativeness;design;Development;education research;Ensure;Goals;improved;Institution;Low income;Mentors;Microbiology;Needs Assessment;Poverty;Preparation;programs;Research;Science;skills;Sorbus;student participation;Students;success;Talents;Time;transfer student;United States National Institutes of Health;Universities;university student

PROJECT_TITLE: Bridges to the Baccalaureate: Cumberland Bridge to Rowan

STUDY_SECTION: TWD

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


NIH_SPENDING_CATS: Aging;Clinical Research;Health Services;Palliative Care

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Project Narrative This program continues to serve as a national resource for training outstanding new investigators in Psycho-oncology.

PI_NAMEs: HAY, JENNIFER L (contact);OSTROFF, JAMIE S.

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TITLE: Psychosocial Palliative and Community Research in Cancer

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Institutional Training and Education Study Section (F)[NCI-F]


ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: OVERALL – PROJECT NARRATIVE The Mayo Clinic Specialized Programs of Research Excellence in Hepatobiliary Cancers, funded by the National Cancer Institute, has developed new tools to improve early detection, diagnosis, and therapeutic treatment for patients facing these deadly liver and biliary malignancies. Each of the three projects and shared resources cores focuses on improving the duration and quality of life for these patients by markedly expanding scientific knowledge, systematic tools, and clinical practice of hepatobiliary cancer medicine.

PI_NAMEs: MC NIVEN, MARK A. (contact);ROBERTS, LEWIS R

PROGRAM_OFFICER_NAME: KUZMIN, IGOR A

PROJECT_TERMS: Accountability;Advocate;Affect;anti-cancer research;Award;base;Basic Science;Biliary;Bioinformatics;Biometry;Blood;Cancer Biology;Cancer Etiology;cancer therapy;CAR T cell therapy;career;Career Choice;career development;Cell Survival;Cessation of life;Chemicals;Childhood;Cholangiocarcinoma;Clinic;Clinical;clinical care;clinical center;clinical efficacy;clinical practice;Clinical Research;Clinical Sciences;Clinical Trials;Collaborations;Combined Modality Therapy;Communication;Communities;community engagement;Comprehensive Cancer Center;Computational Biology;Country;design;Development;Diagnosis;Diagnostic;drug repurposing;Early Diagnosis;Education;Elements;Ensure;experience;Financial Support;Fostering;Foundations;Funding;Genetic Transcription;Genomics;Goals;Hand;Hepatobiliary;hepatobiliary cancer;Immune;Immunotherapeutic agent;immunotherapeutic virotherapy;Immunotherapy;improved;Industry;Infrastructure;inhibitor;innovation;Knowledge;Leadership;Link;Liver;Malignant neoplasm of liver;Malignant Neoplasms;Medicine;Mentorship;Mission;Modeling;National Cancer Institute;neoplastic cell;novel;novel strategies;novel therapeutics;Oncogenic;Oncolytic viruses;organizational structure;Pathology;patient oriented;patient population;patient prognosis;patient response;Patients;Pilot Projects;Positioning Attribute;pre-clinical;Pre-Clinical Model;precision medicine;Prevention;Primary carcinoma of the liver cells;Process;programs;Proteins;Quality of life;Recording of previous events;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;Scientist;Signal Transduction;skills;Sleeping Beauty;Solid;Specialized Program of Research Excellence;standard of care;Structure;success;System;Talents;Technology;Testing;Therapeutic;therapy resistant;tool;translational cancer research;Translational Research;translational research program;treatment response;Trees;Tumor Burden;Tumor Markers;Underrepresented Populations;United States National Institutes of Health;Urine;Vertebral column;Virotherapy;young adult

PROJECT_TITLE: Mayo Clinic Hepatobiliary SPORE

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RPRB-8 (M1)]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Liver Cancer;Liver Disease;Prevention;Rare Diseases

PHR: ADMINISTRATIVE CORE A – PROJECT NARRATIVE This section is not applicable to the Administrative Core.

PI_NAMEs: MC NIVEN, MARK A. (contact)

PROJECT_TERMS: Address;Advocate;Basic Science;Bioinformatics;Biometry;Cancer Patient;career;Cholangiocarcinoma;Clinic;Clinical Management;Clinical Research;Clinical Trials;Collaborations;Communication;Communities;community engagement;Community Outreach;Complement;Comprehensive Cancer Center;Consent;Data;data integration;data management;Decision Making;design;Detection;Development;Education;Educational Activities;Enrollment;Ensure;Evaluation;experience;Funding;Goals;Hepatobiliary;hepatobiliary cancer;improved;Infrastructure;innovation;Institution;Lead;Leadership;Malignant neoplasm of liver;Malignant Neoplasms;meetings;member;Methods;Monitor;multidisciplinary;Occupational activity of managing finances;Office of Administrative Management;operation;organizational structure;patient engagement;Patient Participation;patient population;Patients;Pilot Projects;Policies;Population Heterogeneity;Prevention;programs;Quality Control;recruit;Research;research and development;Research Personnel;Research Project Grants;Resource Sharing;Resources;Science;Secure;Series;Structure;success;System;Translational Research;Translations;Underrepresented Populations;United States National Institutes of Health;Universities

PROJECT_TITLE: Admin Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Genetics;Human Genome;Liver Cancer;Liver Disease;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

PHR: PROJECT 1 – PROJECT NARRATIVE Our ability to understand human cancers has been revolutionized the past two decades by the sequencing of the human genome and the ability to introduce altered genes into cells. This project builds upon this by using the study of a pediatric cancer and a functional precision medicine screen to develop the first diagnostic tests and therapeutic treatments for this cancer.

PI_NAMEs: SIMON, SANFORD M (contact)

PROJECT_TERMS: Acids;addiction;Antibodies;antibody detection;B-Lymphocytes;Biochemical;Biological Assay;Biological Markers;Biological Models;Biology;Biopsy;Blood;C-reactive protein;cancer therapy;Carbamoyl Transferases;Carbamyl Phosphate;Cells;chemotherapy;Childhood Liver Cancer;Chimeric Proteins;Clinic;Clinical;clinical care;Clinical Trials;clinically actionable;clinically relevant;Combined Modality Therapy;Development;Diagnosis;Diagnostic;Diagnostic tests;Disease;Dissociation;DNA;drug repurposing;efficacy evaluation;Enzyme-Linked Immunosorbent Assay;Excision;Fibrolamellar Hepatocellular Carcinoma;Genes;Genetically Engineered Mouse;Genomics;Goals;Hepatobiliary;Histopathology;Human;human genome sequencing;Immunoglobulin G;Immunology;individual patient;individualized medicine;insight;Libraries;liver inflammation;Location;Malignant Childhood Neoplasm;Malignant Epithelial Cell;Malignant neoplasm of liver;Malignant Neoplasms;Maps;metabolome;MicroRNAs;Modality;Molecular;monocyte;Mus;Neoplasm Metastasis;Normal Cell;novel;novel diagnostics;novel therapeutic intervention;novel therapeutics;Nucleotides;Oncogenes;Oncogenic;Oncoproteins;Operative Surgical Procedures;Organoids;Ornithine;overexpression;Pathology;Patient Care;patient derived xenograft model;Patients;peripheral blood;personalized diagnostics;personalized medicine;Pharmaceutical Preparations;Phase I Clinical Trials;Phosphotransferases;Plasma;pre-clinical;Pre-Clinical Model;precision medicine;Precision Medicine Initiative;Predictive Value;PRKACA gene;prognostic value;prospective;Proteins;Proteome;Radiology Specialty;Records;Recurrence;Research;Resected;response;RNA;Scanning;Sensitivity and Specificity;Sorting;Survival Rate;Symptoms;System;Testing;Therapeutic;Therapeutic Agents;therapeutic evaluation;therapeutic target;therapeutically effective;tool;Transcript;transcriptome;Treatment Efficacy;tumor;Tumor Burden;tumor growth;Urine;Vitamin B 12;Work

PROJECT_TITLE: Project 1


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Digestive Diseases - (Gallbladder);Immunotherapy;Liver Cancer;Liver Disease;Rare Diseases

PI_NAMEs: SMOOT, RORY  (contact)

PROJECT_TERMS: Biliary;Binding;Biology;cancer type;carcinogenesis;Cell Death;Cell Survival;Cells;chemotherapy;Cholangiocarcinoma;Cisplatin;Clinic;Clinical;Clinical Trials;Combination Drug Therapy;combinatorial;Complex;Cyclophosphamide;Cytoprotection;Cytotoxic T-Lymphocytes;Data;Dependence;Development;Disease;Down-Regulation;Doxycycline;efficacy evaluation;Event;first-in-human;gemcitabine;Genetic Transcription;granulocyte;Hepatobiliary;Human;Human Cell Line;Immune checkpoint inhibitor;Immune Evasion;Immunocompetent;Immunologic Surveillance;immunoregulation;Immunotherapy;In Vitro;in vivo;in vivo Model;Incidence;Infiltration;inhibitor;innovation;insight;Institution;Interruption;Mediating;Modeling;Molecular;Mouse Cell Line;mouse model;Mus;Myelogenous;Myeloid-derived suppressor cells;novel;novel therapeutic intervention;Nuclear Protein;Oncogenic;paralogous gene;patient derived xenograft model;patient prognosis;Patients;Phase I Clinical Trials;pre-clinical;Pre-Clinical Model;preclinical study;Primary Malignant Neoplasm of Liver;protein activation;protein expression;Protein Inhibition;Proteins;Research Personnel;resistance mechanism;Role;Safety;Signal Transduction;Signaling Protein;Stains;standard of care;Testing;Therapeutic;Therapeutic Effect;Therapeutic Intervention;therapeutic target;therapy resistant;Transcription Coactivator;transcriptomics;Translating;tumor;tumor microenvironment;tumor progression;tumor-immune system interactions;Unresectable

PROJECT_TITLE: Project 2


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

PHR: PROJECT 3 - PROJECT NARRATIVE This research project will develop novel regimens by which the current standard of care (SOC) therapy for hepatocellular cancer (HCC) can be enhanced, and extended to patients who have progressed following first- line Immune Checkpoint Blockade (ICB) therapies. We will do this both by using oncolytic viruses expressing tumor antigens associated with HCC (TAAHCC) to direct populations of highly activated effector T cells into the tumor microenvironment (whose anti-tumor cytotoxic activity can be further enhanced by immune checkpoint blocking molecules, such as anti-PD-L1) and by using our novel technology in which oncolytic viruses loaded onto CAR T cells targeting the TAAHCC GPC3 can be used as potent immunological adjuvants to improve the efficacy of CAR T cell therapy against HCC. Finally, as a prelude to testing clinical efficacy, we will test the safety of a completely novel VSV platform as a means of delivering TAAHCC-targeted viro-immunotherapy in a Phase I clinical study of VSV-CSDE1-GPC3 as therapy in patients with advanced HCC who have received SOC bevacizumab/atezolizumab.

PI_NAMEs: VILE, RICHARD G. (contact)

PROJECT_TERMS: Adjuvant;Algorithms;anti-PD-L1;anti-PD-L1 antibodies;Antibodies;Antigen Targeting;BAY 54-9085;beta catenin;bevacizumab;Binding;Biological Assay;CAR T cell therapy;CD44 gene;CD8-Positive T-Lymphocytes;CD8B1 gene;chimeric antigen receptor T cells;Clinic;Clinical;clinical efficacy;Clinical Research;cofactor;Combined Modality Therapy;CXCR6 gene;cytotoxic;Data;differential expression;effective therapy;Effector Cell;effector T cell;Engineering;Exclusion;FDA approved;first-in-human;Frequencies;Genes;Glypican;Goals;GPC3 gene;Granzyme;Hepatobiliary;Histologic;Human;human disease;human study;Immune;immune cell infiltrate;immune checkpoint;immune checkpoint blockade;Immunologic Adjuvants;Immunologics;Immunosuppression;immunotherapeutic virotherapy;Immunotherapy;improved;in vivo;Infiltration;Inflammatory;Injections;Interferon-beta;Liver;liver cancer model;Mediating;Mus;nanobodies;Nature;new technology;novel;novel therapeutics;Oncogenes;Oncolytic;oncolytic Vesicular Stomatitis Virus;Oncolytic viruses;Pathologic;Patients;PD-1/PD-L1;Phase;Plasmids;Point Mutation;Population;pre-clinical;Primary carcinoma of the liver cells;programmed cell death ligand 1;programmed cell death protein 1;Proteins;Refractory;Regimen;Research Project Grants;Safety;safety testing;Sleeping Beauty;standard of care;synergism;T cell response;T-Lymphocyte;Testing;Therapeutic;Time;transcriptome sequencing;tumor;Tumor Antigens;tumor microenvironment;Vascular Endothelial Growth Factors;Vesicular stomatitis Indiana virus;Viral;Viral Antigens;Viral load measurement;Virotherapy;Virus;Virus Diseases;Xenograft Model

PROJECT_TITLE: Project 3


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Data Science;Digestive Diseases;Genetics;Human Genome;Liver Cancer;Liver Disease;Networking and Information Technology R&D (NITRD);Rare Diseases

PHR: CORE B (BIOSTATISTICS AND BIOINFORMATICS) – PROJECT NARRATIVE The Biostatistics and Bioinformatics Core collaborates with HBC SPORE investigators in designing studies and clinical trials, determining optimal data collection methods, performing data management and quality control, and in analyzing and interpreting study results. The Biostatistics and Bioinformatics Core interacts with the Biospecimen and Pathology Core, ensuring optimal use of resources and outstanding quality research with the utmost reliability.

PI_NAMEs: WANG, CHEN  (contact)

PROJECT_TERMS: Address;anti-cancer research;archive data;Area;ATAC-seq;Bioinformatics;Biological Models;Biometry;Biostatistics Core;Blood;career;Cell Line;Characteristics;Cholangiocarcinoma;Clinic;Clinical;Clinical Trials;Clinical Trials Design;Collaborations;Communities;complex data;Comprehensive Cancer Center;Computational Biology;Computer software;computerized data processing;Consultations;Data;Data Analyses;data archive;Data Collection;Data Discovery;data handling;data management;data quality;Data Reporting;data resource;data reuse;data sharing;Databases;design;Development;DNA sequencing;electronic data;Ensure;Evaluation;experience;Genomics;Goals;Hepatobiliary;hepatobiliary cancer;Human;Individual;Informatics;Information Management;Infrastructure;Institution;Knowledge;Leadership;Link;Malignant Neoplasms;Manuscripts;Medidata;member;Mentors;Metadata;Methodology;Methods;MicroRNAs;Multiomic Data;Normal tissue morphology;Pathology;Pathway Analysis;patient derived xenograft model;Patients;Pilot Projects;Population Study;Predictive Cancer Model;Preparation;Primary carcinoma of the liver cells;programs;Proteomics;public database;quality assurance;Quality Control;Registries;Reproduction spores;Research;Research Design;Research Personnel;research study;Resource Sharing;Resources;Sampling;searchable database;Sequence Alignment;Specialist;Statistical Data Interpretation;System;Techniques;The Cancer Genome Atlas;Tissues;tool;transcriptome sequencing;translational study;tumor;usability;Variant;Work

PROJECT_TITLE: Biostatistics Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Liver Cancer;Liver Disease;Rare Diseases

PHR: BIOSPECIMEN AND PATHOLOGY CORE C – PROJECT NARRATIVE This Core obtains research permission from cancer patients and appropriate normal or control individuals, collects tissues and blood samples, and links the specimens with information about the patient, including their age and gender, risk factors for cancer, response to treatment, and survival. The samples are then made available for the SPORE projects and other investigators studying liver and biliary cancers, to facilitate our understanding of the biological basis of cancer, prevent cancer, and develop new treatments for cancer. Mayo Clinic has one of the world’s largest specimen collections for liver and biliary cancers. We will continue to develop this important resource by expanding our extensive network of national and international collaborators, particularly focusing on specimens from patients living in diverse and underserved communities.

PI_NAMEs: TORBENSON, MICHAEL S (contact)

PROJECT_TERMS: Age;Agreement;Aliquot;Animal Model;anti-cancer research;Arizona;Authorization documentation;Bacterial Artificial Chromosomes;Bile fluid;biobank;Biological;Blood;Blood Platelets;Blood specimen;burden of illness;Cancer Model;Cancer Patient;cancer specimen resource;cancer therapy;career;Cell Line;Cessation of life;Cholangiocarcinoma;Cholestasis;Clinic;Clinical;Clinical Data;Collaborations;Communities;Consent;Core Facility;COVID-19 pandemic;Data;demographics;Development;Diagnostic;Dietary History;digital imaging;disease registry;Dissociation;DNA;early phase clinical trial;Eligibility Determination;Ethics;Family;Feces;Fibrolamellar Hepatocellular Carcinoma;Florida;Formalin;Freezing;Fresh Tissue;Funding;Future;Gender;Genetic;Genomic DNA;Germ Lines;Goals;Hepatobiliary;hepatobiliary cancer;Hepatology;Histology;Human;human tissue;Immunocompetent;immunodeficiency;Immunohistochemistry;Individual;Infrastructure;Institution;Institutional Review Boards;International;Joints;Knock-out;Laboratories;Legal;Link;Liver;liver transplantation;Maintenance;Malignant neoplasm of liver;Malignant Neoplasms;Mayo Clinic Cancer Center;Medical History;Medidata;member;Mission;mouse model;Online Systems;Operating Rooms;Operative Surgical Procedures;Organoids;Outcome;Paraffin;Paraffin Embedding;Pathologic;Pathology;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phenotype;Plasma;Population Heterogeneity;prevent;Primary carcinoma of the liver cells;Process;Program Research Project Grants;programs;prospective;Protocols documentation;Recording of previous events;Registries;repository;Research;Research Personnel;Research Project Grants;Resected;Resource Sharing;Resources;Risk Factors;sample collection;Sampling;Serum;Services;Shipping;single cell sequencing;Site;Sleeping Beauty;Specimen;Stains;success;Surgical Pathology;Time;Tissue Embedding;tissue fixing;Tissue Microarray;Tissue Sample;Tissues;Toxin;Transgenic Organisms;Translational Research;transplant registry;treatment response;tumor;Tumor stage;underserved community;Universities;Urine;virtual

PROJECT_TITLE: Biospecimens Core


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Liver Cancer;Liver Disease;Rare Diseases

PHR: DEVELOPMENTAL RESEARCH PROGRAM – PROJECT NARRATIVE The Developmental Research Program is an important resource to support innovative translational research in liver and biliary cancers. A rigorous process ensures transparency and fair review of applications. The program encourages inter-disciplinary proposals with high payoff potential to rapidly translate new treatment concepts to patients with liver and biliary cancers.

PROJECT_TERMS: Advocate;anti-cancer research;Architecture;Award;Cancer Center;Cancer Etiology;Cessation of life;Cholangiocarcinoma;Clinic;Clinical;Clinical Investigator;Clinical Research;clinically relevant;Collaborations;community engagement;Comprehensive Cancer Center;Death Rate;Development;Developmental Therapeutics Program;Disabled Persons;Ensure;Environment;Epidemiology;Ethnic Population;Evaluation;expectation;experience;Extramural Activities;Fostering;Funding;Funding Agency;Future;Generations;Genetic;Goals;Grant;Hepatobiliary;hepatobiliary cancer;high risk;Immunology;Incidence;Individual;innovation;Institution;Intervention;Laboratories;Leadership;Malignant neoplasm of liver;Malignant Neoplasms;meetings;member;Minority;Monitor;Morbidity - disease rate;mortality;originality;Patients;Peer Review;Pharmacology;Population;Population Sciences;Process;Program Research Project Grants;programs;Qualifying;racial population;recruit;Research;research and development;Research Personnel;Research Project Grants;Research Proposals;Resource Sharing;Resources;Role;Scientist;sound;success;Techniques;Testing;Translating;translational potential;Translational Research;Tumor Biology;Underserved Population;Woman;Work

PROJECT_TITLE: Developmental Research Program


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

PHR: CAREER ENHANCEMENT PROGRAM (CEP) – PROJECT NARRATIVE This section is not applicable to the Career Enhancement Program.

PI_NAMEs: ROBERTS, LEWIS R (contact)

PROJECT_TERMS: Address;anti-cancer research;Architecture;Award;Cancer Center;career;Career Choice;Cholangiocarcinoma;Clinic;Clinical Investigator;Collaborations;Comprehensive Cancer Center;Dedications;Development;Diagnosis;Disabled Persons;Disease;Eligibility Determination;Ethnic Population;Evaluation;expectation;experience;Extramural Activities;Funding;Future;Hepatobiliary;hepatobiliary cancer;Individual;Institution;K-Series Research Career Programs;Leadership;Malignant neoplasm of liver;medical schools;meetings;Mentors;Mentorship;Minnesota;Minority;Monitor;Morbidity - disease rate;mortality;National Cancer Institute;outreach;Positioning Attribute;Prevention;Problem Solving;Process;programs;Qualifying;recruit;Research Personnel;Resources;Role;Science;Scientist;Source;success;synergism;Talents;Translational Research;translational scientist;Underserved Population;Universities;Woman;Work

PROJECT_TITLE: Career Enhancement Program


ORG_CITY: STANFORD

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE (OVERALL) New targeted cancer drugs have transformed care for patients, but they can lead to heart disease as an unintended consequence for some patients. This Program Project uses a synergistic, multi-disciplinary approach using mouse- and cell-based models to understand how heart-related side effects occur and to create a new platform for testing future therapeutics. This ultimately has critical implications for precision medicine to better manage cancer patients who could be susceptible to side effects resulting from cancer therapeutics.

PI_NAMEs: WU, JOSEPH C. (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Acute;Address;Adverse effects;Antineoplastic Agents;Area;Basic Science;cancer care;Cancer Patient;Cardiomyopathies;cardioprotection;Cardiotoxicity;Cardiovascular system;Caring;Cells;Chemicals;Chromosome Mapping;Chronic;Clinical;Clinical Management;Data;drug development;epigenomics;Explosion;Exposure to;Functional disorder;Funding;Future;Genetic;Genetic Predisposition to Disease;Genotype;Gleevec;Goals;Heart;Heart Diseases;Imatinib;improved;Individual Differences;induced pluripotent stem cell;interdisciplinary approach;kinase inhibitor;leukemia treatment;Malignant Neoplasms;Methods;Modeling;mouse model;multidisciplinary;Mus;novel;novel therapeutics;Oncology;Patient Care;Patient Recruitments;patient subsets;Patients;Pharmaceutical Preparations;Phenotype;Phosphotransferases;Population;Population Study;Positioning Attribute;pre-clinical;precision medicine;Prediction of Response to Therapy;Predisposition;Prevention strategy;Program Research Project Grants;programs;receptor;repository;Research;Research Personnel;response;Risk;risk stratification;Science;Secondary Myocardial Diseases;Secondary to;Shotguns;side effect;small molecule;surveillance strategy;synergism;System;Testing;Therapeutic;Toxic effect

PROJECT_TITLE: Multiscale Systems to Elucidate Susceptibility and Cardioprotective Mechanisms in Cardio-oncology


NIH_SPENDING_CATS: Cardiovascular;Telehealth

PROJECT_TERMS: Administrator;cardioprotection;Cardiovascular system;Collaborations;Ensure;Goals;Grant;meetings;member;Oncology;Persons;Predisposition;Program Research Project Grants;programs;Reporting;research and development;Research Personnel;synergism;System;Videoconferencing;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PI_NAMEs: SALLAM, KARIM  (contact)

PROJECT_TERMS: Address;Adverse effects;Agammaglobulinaemia tyrosine kinase;biobank;cardioprotection;Cardiotoxicity;Cell Line;Chromosome Mapping;Cities;Clinic;Clinical;Clinical Data;clinically relevant;cohort;Collaborations;Collecting Cell;Communities;Complex;Data;data sharing;empowerment;Ensure;Equity;experience;Fostering;Freezing;Gender;Generations;Genetic;Genetic Variation;genome sequencing;Goals;human induced pluripotent stem cells;Individual;Individual Differences;induced pluripotent stem cell;Infrastructure;interest;Link;Malignant Neoplasms;Mission;Oncology;Outcomes Research;participant enrollment;patient derived induced pluripotent stem cells;patient population;Patient Recruitments;Patients;Peripheral Blood Mononuclear Cell;Predisposition;Procedures;Process;Program Research Project Grants;programs;protective pathway;Quality Control;Race;racial diversity;Recovery;recruit;Research;Research Personnel;Resistance;Resources;response;Role;Sampling;Sendai virus;Sex Distribution;Standardization;System;Therapeutic;Tyrosine Kinase Inhibitor;whole genome

PROJECT_TITLE: iPSC Processing Core


NIH_SPENDING_CATS: Cancer;Cardiovascular;Heart Disease;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PROJECT_TERMS: Agammaglobulinaemia tyrosine kinase;Arrhythmia;Atrial Fibrillation;B lymphoid malignancy;Binding;cancer therapy;Cardiac;Cardiac Myocytes;cardioprotection;Cardiotoxicity;cardiovascular effects;Cardiovascular system;Cells;Clinical;clinical heterogeneity;clinical practice;CRISPR/Cas technology;Databases;Drug Modelings;Drug Screening;Drug toxicity;Electrophysiology (science);Generations;Genetic;Genomics;Homeostasis;human induced pluripotent stem cells;induced pluripotent stem cell;inhibitor;inhibitor therapy;International;kinase inhibitor;Malignant Neoplasms;Maps;Mediating;Mediator;Methods;Modeling;mouse model;mutant;novel;Oncology;Optics;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacovigilance;Phosphotransferases;Play;pre-clinical;Pre-Clinical Model;Predisposition;protein-tyrosine kinase c-src;Risk;Risk Factors;Role;small molecule;src-Family Kinases;stem cell biology;success;Syndrome;synergism;System;Testing;theories;tool;Toxic effect;Transgenic Mice;Tyrosine Kinase Inhibitor

PROJECT_TITLE: Mechanisms of Cardiotoxicity Associated with Covalent Kinase Inhibitors


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Cardiovascular;Clinical Research;Genetics;Heart Disease;Human Genome;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PROJECT_TERMS: 3-Dimensional;Address;Adverse drug effect;Affect;Aftercare;Animals;Antineoplastic Agents;Biological Assay;Biology;Cancer Patient;cancer therapy;Cardiac;Cardiac Myocytes;cardioprotection;Cardiotoxicity;Cardiovascular Diseases;Cardiovascular system;causal variant;Cause of Death;Cell Line;Cells;chemotherapy;Cities;Collaborations;Development;Dose;Drug Screening;Electrophysiology (science);Endothelial Cells;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;epigenome;Etiology;experimental study;Fibroblasts;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Generations;Genes;Genetic;Genetic Predisposition to Disease;Genetic Screening;Genetic study;Genetic Transcription;genetic variant;genome editing;genome sequencing;genome-wide;Genomics;genotyped patients;Grant;In Vitro;Individual;induced pluripotent stem cell;inhibitor therapy;kinase inhibitor;Malignant Neoplasms;Maps;Measures;Metabolism;meter;Methodology;Modeling;Monitor;mortality;multiple omics;novel;Oncology;Organoids;Pathway interactions;patient derived induced pluripotent stem cells;patient variability;Patients;Pharmaceutical Preparations;Polymorphism Analysis;Population;Population Study;Predisposition;Process;Property;protective pathway;Quantitative Trait Loci;Reactive Oxygen Species;Recovery;recruit;response;Sampling;screening;Series;single cell analysis;Single Nucleotide Polymorphism;single nucleus RNA-sequencing;Site;stem cell biology;System;targeted cancer therapy;Technology;three-dimensional modeling;Tissues;Toxic effect;transcriptome;Tyrosine Kinase Inhibitor;Variant;variant detection;whole genome;XCL1 gene

PROJECT_TITLE: Elucidating Genetic Susceptibility of Covalent Kinase Inhibitors with iPSC "Cell Village"


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Cardiovascular;Genetics;Heart Disease;Human Genome;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PI_NAMEs: MERCOLA, MARK  (contact)

PROJECT_TERMS: Adult;Advanced Development;Adverse drug effect;Adverse effects;Affect;Agammaglobulinaemia tyrosine kinase;Arrhythmia;ATAC-seq;Atrial Fibrillation;B lymphoid malignancy;Binding;Biological;Biological Assay;Cancer Patient;Cancer Survivorship;cancer therapy;Cardiac Myocytes;cardioprotection;Cardiotoxicity;Cardiovascular system;Cells;Chemicals;Chromatin;Chromatin Remodeling Factor;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Collaborations;Complement;CRISPR interference;CRISPR-mediated transcriptional activation;Data;deep learning algorithm;Distant;DNA;Dose;Elements;epigenomic profiling;epigenomics;Exhibits;experimental study;Exposure to;functional genomics;gene discovery;Generations;Genes;Genetic;Genetic Transcription;Genomic approach;Heart;Heart Atrium;high throughput screening;Human;Human Genetics;human induced pluripotent stem cells;improved;in vivo;Incidence;inhibitor;Joints;kinase inhibitor;knock-down;Knock-out;Life;Mediating;Modeling;Modernization;Molecular Target;mouse model;Mus;muscle enhancer factor-2A;Oncology;overexpression;Patients;Pharmaceutical Preparations;pharmacologic;Predisposition;Program Research Project Grants;Quality of life;Receptor Protein-Tyrosine Kinases;Regulator Genes;Regulatory Element;Risk;Role;screening;small molecule;Specificity;Susceptibility Gene;synergism;System;Testing;Therapeutic;therapeutic target;tool;Toxic effect;transcription factor;Treatment Efficacy;Tyrosine Kinase Inhibitor;vector;Ventricular;Ventricular Arrhythmia;XCL1 gene

PROJECT_TITLE: Elucidating Protective Mechanisms for Cardiotoxicity of Kinase Inhibitors


ORG_CITY: ALBUQUERQUE

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: PROJECT NARRATIVE Damaged lysosomes and dysfunctional stress granules have become increasingly associated with a wide range of human diseases and have important clinical applications. Pioneering research I conducted before achieving an independent faculty position was the first to demonstrate that lysosomal damage triggers stress granule formation. The proposed research will elevate these findings by providing insight into the relationship between lysosomal damage and stress granule formation, thereby offering the potential to promote significant advancements in therapeutic interventions.

PI_NAMEs: CASSANO, JINGYUE JIA (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TITLE: Cellular Mechanisms of Lysosomal Damage Response

STUDY_SECTION: MRAD

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - D Study Section[MRAD]


ORG_CITY: SAN FRANCISCO

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: OVERALL: NARRATIVE The WISDOM Study, opened in 2016, is the first large clinical trial of a new, personalized approach to breast cancer screening in which women receive individualized screening recommendations based on their personal risk for breast cancer. While our initial efforts were focused on showing that personalized screening was as safe, less morbid, preferred and more likely to result in uptake of preventive strategies in comparison to annual screening, we will now focus on using advances in polygenic risk models and mammographic AI to improve our ability to predict risk for developing fast or slow growing breast cancer subtypes, and tailoring screening and prevention strategies accordingly. Four closely integrated projects will enable us to work toward the goal of a personalized breast cancer screening program that is more effective and efficient, and more likely to help find serious breast cancers early, when they are more likely to be treated successfully, and decrease the incidence of slow growing cancers.

PI_NAMEs: ESSERMAN, LAURA J (contact);VAN'T VEER, LAURA J

PROGRAM_OFFICER_NAME: HECKMAN-STODDARD, BRANDY

PROJECT_TERMS: 3-Dimensional;Age;Algorithms;artificial intelligence model;Bioinformatics;Biology;Breast Cancer Detection;Breast Cancer Model;Breast Cancer Risk Factor;breast density;Cancer Intervention and Surveillance Modeling Network;cancer invasiveness;cancer subtypes;cancer type;Cessation of life;Classification;Clinical;clinical risk;Clinical Trials;cohort;Cohort Studies;Collaborations;Complex;cost effectiveness;Coupled;Data;deep learning;Detection;Development;Discipline;Disease;Early Diagnosis;Effectiveness;efficacy evaluation;Enrollment;Epidemiologic Factors;Ethnic Origin;Evaluation;experience;Genetic;genomic predictors;Genomics;Germ Lines;Germ-Line Mutation;Goals;Harm Reduction;Healthcare;High Risk Woman;Image;implementation science;improved;Incidence;Individual;individualized prevention;Knowledge;learning progression;Lesion;Malignant Breast Neoplasm;Malignant Neoplasms;Mammography;Modeling;mortality;mutation carrier;Patient-Focused Outcomes;Penetrance;Performance;personalized approach;personalized screening;polygenic risk score;Population;precision medicine;predictive modeling;Predisposition;Prevention;Prevention strategy;preventive intervention;programs;Race;radiomics;Recommendation;Recurrence;Research;Resources;Risk;Risk Assessment;Risk Factors;Risk Marker;risk prediction;Risk Reduction;risk stratification;routine screening;Science;Scientific Advances and Accomplishments;screening;screening guidelines;screening program;Site;statistics;Testing;Time;tool;tumor;Update;uptake;Woman;Work

PROJECT_TITLE: WISDOM: A platform to optimize subtype-specific screening and prevention

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RPRB-T (M1)]


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

PHR: CORE A: NARRATIVE The overall goal of the Program Project is to develop and study improvements in breast cancer risk assessment and use these to see how they can make breast cancer screening better. The Administration, Communication and Project Management Core will be responsible for overall project management and communications, partnership development with payors, stakeholder engagement, dissemination of educational materials, and will facilitate the successful transition of products and models developed within the projects to support WISDOM protocol development and implementation.

PI_NAMEs: FISCALINI, ALLISON STOVER (contact)

PROJECT_TERMS: Advocate;Area;Biological Markers;Breast Cancer Detection;Breast Cancer Risk Factor;Budgets;Clinical Trials;cohort;Collaborations;Communication;Communities;community engagement;Complex;cost effectiveness;Data;Data Collection;Development;Dissemination and Implementation;Education;Educational Materials;Ensure;experience;Genomics;Goals;Image;improved;Individual;Information Systems;Institutional Review Boards;Leadership;Maintenance;meetings;Modeling;multidisciplinary;Outcome;Participant;Population;Prevention;Privatization;Procedures;Process;programs;prospective;protocol development;provider networks;recruit;Reporting;repository;Research Personnel;Resources;Risk;Risk Assessment;Role;Scientific Advances and Accomplishments;screening;screening guidelines;Specimen;success;System;Testing;Time;tool;Training;Underrepresented Populations;Update;Validation;Voice;webinar

PROJECT_TITLE: Core A: Administration, Communication and Project Management