ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative The Jumonji histone demethylases are enzymes that drive cancer’s uncontrolled growth and allow cancer cells to adapt to therapeutic toxic stress, surviving it. Here we propose to define how a key Jumonji enzyme in lung cancer gets activated when DNA is damaged with radiation therapy and to find ways to block the activity of this enzyme in order to sensitize non-small cell lung cancers to radiation, overcoming radiation resistance. Our goal is to make lung tumors exquisitely responsive to radiation therapy locally, without any damage to normal tissue.

PI_NAMEs: MARTINEZ, ELISABETH D (contact)

PROGRAM_OFFICER_NAME: SHARMAN, ANU

PROJECT_TERMS: Alanine;Aspartic Acid;ataxia telangiectasia mutated protein;cancer cell;Cancer Patient;Cell Death;Cell Line;Cell Survival;Cells;Chromatin;Consensus Sequence;demethylation;DNA;DNA Damage;DNA Repair;DNA Repair Pathway;enzyme activity;enzyme substrate;Enzymes;Epigenetic Process;Exposure to;Foundations;gain of function;Genetic Transcription;Genomics;Glutamic Acid;Goals;Grant;Growth;histone demethylase;Histones;homologous recombination;In Vitro;inhibitor;Ionizing radiation;KDM5B gene;knock-down;Knock-out;Local Therapy;loss of function;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Measures;Mediating;Modernization;Molecular;Mutate;Non-Small-Cell Lung Carcinoma;Nonhomologous DNA End Joining;Normal tissue morphology;novel;novel strategies;Oncogenic;overexpression;palliative;Pathway interactions;Phosphorylation;Phosphorylation Site;Phosphotransferases;Positioning Attribute;Post-Translational Protein Processing;Predisposition;Radiation;radiation resistance;Radiation therapy;recruit;repaired;Resistance;Resolution;response;Role;Signal Transduction;Site;Stress;Therapeutic;Treatment Protocols;tumor;Tumor Tissue

PROJECT_TITLE: Post-translational modifications control JARID enzyme activity during DNA damage


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: HOSPITALS

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Cervical Cancer;Clinical Research;Genetics;Human Genome;Precision Medicine;Radiation Oncology;Women's Health Research

ORG_CITY: HOUSTON

ORG_COUNTRY: UNITED STATES

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: Project Narrative This project aims to validate potential targets for chemoradiation sensitization in patients with cervical cancer undergoing chemoradiation for cure. This will be accomplished by testing previously identified potential targets in cervical cancer cell lines and organoid models and by computationally validating mutations that expand during CRT in patients undergoing treatment. This proposal uses a novel, non-invasive swab-based biopsy method to collect serial data without harm or discomfort to patients, which is the first approach in cervical cancer.

PI_NAMEs: COLBERT, LAUREN ELIZABETH (contact)

PROGRAM_OFFICER_NAME: PRASANNA, PAT G

PROJECT_TERMS: Address;Aftercare;biobank;Biological Models;Biopsy;Blood Banks;Cancer cell line;Cancer Patient;Candidate Disease Gene;candidate validation;Cause of Death;cell bank;Cell Line;Cervical;chemoradiation;Chemotherapy and/or radiation;Clinic;Clinical;clinical translation;Clonal Expansion;cohort;computational pipelines;CRISPR library;Custom;Data;Databases;Dimensions;DNA Library;DNA Sequence Alteration;driver mutation;Drug Screening;Evolution;exome sequencing;experience;Fistula;Freezing;Fresh Tissue;Future;Gene Pool;Genes;genetic testing;Hemorrhage;high risk;human tissue;Immune;improved;In Vitro;in vitro testing;Institution;Laboratories;large-scale database;Libraries;Malignant neoplasm of cervix uteri;Malignant Neoplasms;Methods;microbiome;Modeling;Mutate;Mutation;new therapeutic target;novel;Organoids;Pathway interactions;patient population;Patients;Pharmaceutical Preparations;Pharmacotherapy;Pilot Projects;Population;Precision therapeutics;predictive marker;Prognostic Marker;Publishing;Qualifying;radiation resistance;radiation response;Radiation-Sensitizing Agents;Radiosensitization;Recording of previous events;Relapse;research clinical testing;Resistance;response;Risk;risk variant;Sampling;screening;single-cell RNA sequencing;standard of care;Swab;targeted agent;targeted treatment;Techniques;Testing;therapeutically effective;Tissue Banks;Tissues;Translating;Treatment outcome;tumor;tumorigenesis;Woman;Women's mortality

PROJECT_TITLE: Identifying Novel Radiation Sensitizers in Cervical Cancer


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prostate Cancer;Racial and Ethnic Minority Health Research;Social Determinants of Health;Urologic Diseases

ORG_CITY: Loma Linda

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: LOMA LINDA UNIVERSITY

ORG_STATE: CA

PHR: NARRATIVE Men of African ancestry have a higher incidence and mortality from prostate cancer (PCa) than men of European ancestry. There is currently an urgency to understand the molecular mechanisms underlying these race-related differences and to harness them for identifying novel therapeutic targets. The high mortality of advanced PCa is attributed to therapy resistance, thus there is also an urgent clinical need to develop innovative approaches to circumvent this resistance. The proposed study will uncover the molecular basis for specific race-related differences in PCa immunobiology, which could provide key insights into immune determinants contributing to PCa mortality disparities. The study will also establish the glycolytic enzyme Enolase as a potential therapeutic and theranostic target for advanced PCa, which could lead to innovative clinical strategies to reduce overall PCa mortality disparities.

PI_NAMEs: ALMAGUEL, FRANKIE G;CASIANO, CARLOS A. (contact);DAS, BHASKAR CHANDRA

PROGRAM_OFFICER_NAME: WALLACE, TIFFANY A

PROJECT_TERMS: Active Sites;advanced prostate cancer;Affect;African ancestry;anti-tumor immune response;antitumor effect;Autoantibodies;Biological;Biological Markers;Biological Testing;Boron;cancer biomarkers;cancer gene expression;cancer health disparity;cancer immunobiology;Cell surface;Cells;Characteristics;Chemoresistance;Clinical;clinical effect;Clinical Research;design;Development;Diagnostic;Diagnostic Imaging;differential expression;Disparity;Effectiveness;enolase;Enzymes;European ancestry;FOLH1 gene;Future;Genes;Genetic;Homology Modeling;Image;Immune;Immune response;Immune Targeting;immunoreactivity;Incidence;Inflammatory;innovation;insight;Invaded;Lead;Libraries;Life Style;Malignant neoplasm of prostate;men;Metabolism;Metastatic Prostate Cancer;migration;Molecular;mortality;mortality disparity;nanomolar;Neoplasm Metastasis;neoplastic cell;neuroendocrine differentiation;new therapeutic target;novel;novel therapeutics;Organoids;Outcome;Pathway interactions;patient derived xenograft model;patient subsets;Patients;Permeability;pharmacokinetics and pharmacodynamics;pharmacophore;Positron-Emission Tomography;Post-Translational Protein Processing;Pre-Clinical Model;Process;Proliferating;Property;prostate cancer cell;prostate cancer cell line;prostate cancer model;Prostatic Neoplasms;Protein Isoforms;Proteins;Race;racial difference;racial disparity;racial diversity;Radiolabeled;Radionuclide therapy;Resistance;response;Role;small molecule;small molecule inhibitor;socioeconomics;Specificity;Structure-Activity Relationship;Surface;Surface Antigens;taxane;Testing;theranostics;Therapeutic;therapy resistant;tomography;Toxic effect;transcriptome sequencing;tumor;Tumor Antigens;X-Ray Computed Tomography

PROJECT_TITLE: Role and Theranostics Potential of Enolase in Prostate Cancer Health Disparities


ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE In the US, approximately 1 in every 2-3 individuals will develop cancer, a disease of uncontrolled cellular proliferation that can be fatal. The TP53 gene is the most commonly mutated gene in human cancer, reflecting the fact that p53 plays an essential role as a tumor suppressor. This research aims to elucidate the mechanisms by which p53 acts to suppress cancer, with the ultimate goal of improving early detection and treatment of cancer.

PI_NAMEs: ATTARDI, LAURA D (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: Acute;Affect;Alternative Splicing;Alveolar;Biological Assay;cancer cell;cancer therapy;carcinogenesis;Cell Differentiation process;Cell Proliferation;Cells;CRISPR screen;Disease;DNA Damage;Early Diagnosis;Early treatment;Event;Evolution;Genes;Genetic Transcription;Goals;Human;improved;in vivo;Individual;insight;Kinetics;KRASG12D;Lung Adenocarcinoma;lung injury;lung regeneration;Malignant Neoplasms;Mediating;Molecular;mouse model;Mus;Mutant Strains Mice;Mutate;novel;Pathway interactions;Play;posttranscriptional;Primary carcinoma of the liver cells;programs;Proteome;Proteomics;Research;response;RNA Splicing;RNA-Binding Proteins;Role;single cell ATAC-seq;single-cell RNA sequencing;small hairpin RNA;standard of care;targeted treatment;Testing;Therapeutic;TP53 gene;Transcriptional Activation Domain;tumor;tumor barcoding and sequencing;tumor microenvironment;Tumor Suppression;Tumor Suppressor Genes;Tumor Suppressor Proteins;Work;Zinc Fingers

PROJECT_TITLE: Integrative approaches to elucidate p53 transcriptional networks during carcinogenesis


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Hematology;Pancreatic Cancer;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Narrative The primary focus of my work has been to understand the mechanisms by which cancers subvert normal developmental and stem cell signals to grow, spread and evade therapy. Over the last decade our work has ranged from discovery of new signals involved in cancer growth and progression to preclinical work that has formed the basis of clinical trials testing new agents for drug-resistant leukemias – leading to the recent approval of Glasdegib to treat aggressive leukemia – and pancreatic cancer. In the coming years, we will continue to strive to make important contributions that will have a meaningful impact on the many lives that deeply depend on the discoveries we make as a community.

PI_NAMEs: REYA, TANNISHTHA  (contact)

PROGRAM_OFFICER_NAME: HILDESHEIM, JEFFREY

PROJECT_TERMS: Benign;Cancer Biology;Cancer Control;cancer heterogeneity;cancer initiation;Cancer Relapse;cancer therapy;Cells;Clinical Trials;Communities;Development;Drug resistance;Early Diagnosis;Evolution;Growth;Hematologic Neoplasms;Image;improved;Lesion;leukemia;Malignant neoplasm of pancreas;Malignant Neoplasms;Molecular;New Agents;Patient-Focused Outcomes;pre-clinical;programs;Recurrent disease;Regulation;Research;Role;Signal Transduction;stem cells;Testing;therapy resistant;tumor progression;Undifferentiated;Work

PROJECT_TITLE: Molecular strategies for early detection and targeting of cancer


NIH_SPENDING_CATS: Aging;Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Genetics;Human Genome;Prevention;Women's Health Research

ORG_CITY: BOSTON

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: Project Narrative: The only effective means of breast cancer prevention in women with inherited BRCA mutations is prophylactic mastectomy, which, while effective, raises issues relating to quality of life and other psychological and physical consequences. The overarching objective of this application is to develop strategies to detect and eliminate pre-malignant cells in breast tissues from high-risk women. To accomplish this goal, we have used state-of- the-art single-cell technologies to detect and isolate subpopulations of breast cells that accumulate in BRCA1 and BRCA2 mutation carriers and propose studies to determine how these subpopulations contribute to tumor development and what causes their accumulation in order to develop strategies to interfere with cancer development in high-risk women.

PI_NAMEs: BRUGGE, JOAN SIEFERT (contact)

PROJECT_TERMS: brca gene;BRCA mutations;BRCA1 gene;BRCA1 Mutation;BRCA2 gene;BRCA2 Mutation;Breast;Breast Cancer Prevention;Breast Cancer Risk Factor;Cell Lineage;Cell Proliferation;Cells;Cytometry;Development;diagnostic strategy;DNA Damage;Evolution;Goals;high risk;high risk population;High Risk Woman;High-Risk Cancer;Histology;Human;Image;Immunocompromised Host;Immunofluorescence Immunologic;In Situ;Inherited;Intervention;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary Gland Parenchyma;Mammary Neoplasms;Masks;Mus;mutant;Mutation;mutation carrier;novel diagnostics;Organoids;Periodicity;Population;Population Analysis;premalignant;Premalignant Cell;Premalignant Change;prevent;programs;Proliferation Marker;prophylactic;prophylactic mastectomy;psychologic;Quality of life;reconstitution;RNA;single cell analysis;single cell technology;single-cell RNA sequencing;Structure;Surface;Susceptibility Gene;Technology;Tissues;tool;tumor;tumor progression;tumorigenesis;Woman;women's prevention

PROJECT_TITLE: Tracking the evolution of breast cancer through single cell analyses of premalignant breast tissues from women at high risk for cancer development


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Prevention;Social Determinants of Health

ORG_CITY: AMHERST

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: Narrative Our research demonstrated that a mobile produce market can have a significant positive impact on diets of residents in lower-income communities. We want to test this program more widely to determine if the effect can be replicated and develop a best-practices toolkit to help others sustainably implement the program.

PI_NAMEs: LEONE, LUCIA A (contact)

PROGRAM_OFFICER_NAME: AGURS-COLLINS, TANYA

PROJECT_TERMS: Behavior Therapy;Body mass index;Businesses;Carotenoids;Chronic;cluster randomized design;Cluster randomized trial;Communities;community college;community engaged approach;community engagement;community organizations;Community Outreach;Computer software;Consumption;Control Groups;cooking;cost;Country;Data;Dermal;design;Diet;dietary;Dose;Eating;Education;Effectiveness;effectiveness measure;effectiveness testing;effectiveness/implementation hybrid;environmental intervention;Evaluation;Face;farmers markets;Fatty acid glycerol esters;Feedback;Fingers;flexibility;follow-up;Food;Food Access;food environment;Food Preferences;fruits and vegetables;Funding;Future;Health;health disparity;Health Food;Healthy Eating;Heart Diseases;Height;Hour;Housing;hybrid type 1 design;implementation framework;implementation process;Improve Access;improved;Income;Individual;informant;Intake;Intervention;intervention participants;Interview;Knowledge;Low income;Low Income Population;Malignant Neoplasms;Marketing;Measurement;Measures;member;Minority;Minority Groups;Modeling;Neighborhood Health Center;Neighborhoods;Nonprofit Organizations;North Carolina;nutrition education;Obesity;Outcome;Participant;Patient Self-Report;Periodicals;Persons;Population;Preparation;Price;Process;process evaluation;Process Measure;Program Effectiveness;programs;Qualifying;Randomized;Randomized, Controlled Trials;recruit;Reporting;Request for Proposals;Research;research study;Running;Sales;saturated fat;Scanning;Selection Criteria;Self Efficacy;Site;skills;social cognitive theory;Socioeconomic Status;Sodium;success;sugar;Surveys;Techniques;Telephone;Testing;theories;Time;underserved community;Unhealthy Diet;Update;Vulnerable Populations;Weight

PROJECT_TITLE: Effectiveness and Implementation of a Research Tested Mobile Produce Market Designed to Improve Diet in Underserved Communities


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

ORG_NAME: DANA-FARBER CANCER INST

PHR: PROJECT NARRATIVE Death from chemoresistant germ cell tumors (GCTs) account for the greatest number of life years lost of any non-childhood malignancy, and the origins and evolution to chemoresistance in this disease are incompletely characterized. We have developed data identifying reciprocal loss of heterozygosity (RLOH) as a disease- defining genomic defect in GCTs, presence of apoptotic priming underlying the more typical chemosensitivity, and accumulation of RLOH as GCTs evolve towards chemoresistance. Through the use of several novel molecular techniques applied directly to patient specimens, this proposal will enable this program to develop a more complete understanding of the factors driving oncogenesis and evolution to chemoresistance in this rare cancer, with the plan to translate targets revealed through this study to therapeutic development in this area of unmet medical need.

PI_NAMEs: VAN ALLEN, ELIEZER M (contact)

PROJECT_TERMS: Acceleration;Activities of Daily Living;Address;Affect;Algorithms;Alleles;Apoptosis;Apoptotic;Area;arm;Automobile Driving;Award;Biological Assay;Biology;Cancer Biology;Cancer Center;cancer genetics;cancer type;Cessation of life;Chemoresistance;chemotherapy;Chromosomes;Clinical;Clinical assessments;clinically actionable;Computational algorithm;Computational Biology;Dana-Farber Cancer Institute;Data;Defect;Development;Diagnosis;Disease;disease model;disorder risk;Dissection;DNA;DNA copy number;Early identification;Epigenetic Process;epigenetic silencing;epigenome;Event;Evolution;Exhibits;experimental study;Foundations;Genes;Genetic;Genetic Processes;Genetic Transcription;Genome;genome analysis;Genomics;Germ cell tumor;Germ Lines;Goals;high risk;Human;Individual;Infrastructure;innovation;Institution;Interdisciplinary Study;International;Investigation;Life Expectancy;Loss of Heterozygosity;Malignant Neoplasms;Mediastinum;Medical;Meiosis;Meiotic Recombination;Mitochondria;Modeling;Molecular;Molecular Analysis;mortality;Mutation;new therapeutic target;novel;Oncogenic;Oncology;Outcome;Ovary;patient oriented;patient stratification;Patients;Pattern;Persons;Phenotype;Platinum;pluripotency;Pre-Clinical Model;Predisposition;Procedures;prognostic;programs;rare cancer;Recurrence;Refractory Disease;relapse prediction;Research;Resistance;Resources;Sampling;Sentinel;Somatic Mutation;Specimen;Stratification;Study models;Techniques;Testicular Germ Cell Tumor;Testis;Therapeutic;therapeutic development;therapy resistant;transcriptomics;Translating;Translations;treatment strategy;tumor;tumor initiation;tumor progression;tumorigenesis;Urogenital Cancer;Work;years of life lost;young man

PROJECT_TITLE: Molecular origins and evolution to chemoresistance in germ cell tumors


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome;Orphan Drug;Precision Medicine;Radiation Oncology;Rare Diseases

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Rectal cancer represents a growing problem, because it is increasingly diagnosed in people in the prime of life; however, research into new treatments has been hampered because current models of rectal cancer poorly represent patient tumors. Our goal is to develop rectal cancer organoids (tumoroids) as models for rectal cancer research and to establish whether the tumoroids allow for prediction of individual patients' responses to the components of standard treatment, including chemotherapy or radiotherapy. The ultimate result will be expansion of patient-specific research tools, accelerated discovery of new treatment options for rectal cancer patients, and eventually better treatment decisions for individual patients.

PI_NAMEs: SMITH, JESSE JOSHUA  (contact)

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: 3-Dimensional;Acceleration;Address;Affect;Anatomy;anti-cancer research;biobank;Bioinformatics;Biology;Biometry;cancer genomics;Cancer Patient;cBioPortal;Cell Culture Techniques;Cell Line;chemotherapy;Chemotherapy and/or radiation;Clinical;clinically relevant;Collection;colon cancer cell line;Colorectal Surgery;Communities;Complex;Credentialing;Data;Development;Diagnosis;Disease;effective therapy;Environment;flexibility;Gene Expression;Genitourinary system;Genomics;Goals;Histology;Human;Implant;implantation;in vivo;in vivo Model;Incidence;Individual;individual patient;individual response;Injections;Institution;interest;Invaded;Investigation;KRAS2 gene;Life;Location;Malignant Neoplasms;Memorial Sloan-Kettering Cancer Center;Modeling;Molecular;mouse model;Mus;Mutation;Neoadjuvant Therapy;Neoplasm Metastasis;Operative Surgical Procedures;Organ;Organoids;Pathologic;Pathology;patient derived xenograft model;patient response;Patient Selection;Patients;Pelvis;Persons;Physiological;pilot test;pre-clinical;predicting response;predictive tools;Quality of life;Radiation;Radiation Oncology;Radiation therapy;Rectal Adenocarcinoma;Rectal Cancer;Rectum;repository;Research;Resources;response;Selection for Treatments;standard care;standard of care;subcutaneous;success;Surgical Oncology;survival outcome;Testing;tool;TP53 gene;trait;transcriptome;Transplantation;treatment response;tumor;Tumor Tissue;two-dimensional

PROJECT_TITLE: Expansion of Tumoroid Models for Precise Treatment of the Rectal Cancer Patient

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


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Colorectal Cancer;Complementary and Integrative Health;Digestive Diseases;Nutrition;Physical Activity;Prevention;Rehabilitation;Social Determinants of Health;Telehealth

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Colorectal cancer is the 2nd leading cause of cancer death in the United States. A lifestyle consistent with the American Cancer Society (ACS) Nutrition and Physical Activity Guidelines is associated with approximately 40% lower risk of death in people with colorectal cancer, but few colorectal cancer survivors follow the guidelines. This study will use an innovative framework to identify an intervention to improve physical activity, diet, and body size among colorectal cancer survivors that can be remotely delivered and broadly accessible.

PI_NAMEs: VAN BLARIGAN, ERIN LYNN (contact)

PROJECT_TERMS: Accelerometer;Address;Affect;Age;American Cancer Society;Behavior;behavior change;Behavior Therapy;Behavioral;Biological;Biology;Body mass index;Body Size;California;Cancer Etiology;cancer recurrence;cancer survival;Cancer Survivor;Cessation of life;Clinical;colon cancer patients;Colon Carcinoma;Colorectal Cancer;colorectal cancer risk;Counseling;Dana-Farber Cancer Institute;Data;design;Diagnosis;Diet;Dietary Fiber;digital health;Disinhibition;effective intervention;Effectiveness;end of life;Engineering;Enrollment;Ethnic Origin;expectation;experience;experimental study;Family;Fasting;Friends;Fruit;Gender;Glucose;Goals;good diet;Guidelines;Health;improved;Individual;inflammatory marker;innovation;Insulin;Interleukin-6;Intervention;Life Style;lifestyle intervention;Literature;Malignant Neoplasms;Measurable;Measures;Mediating;Mediator;men;Mental Depression;Monitor;mortality;mortality risk;multiphase optimization strategy;nutrition;Outcome;Participant;Patients;pedometer;Persons;Physical activity;Physical Function;Population;prevent;primary outcome;Printing;psychologic;Public Health;Race;Randomized;Randomized, Controlled Trials;Recommendation;remote delivery;remote intervention;Reporting;Research;Research Personnel;Resources;San Francisco;Self Efficacy;self reported behavior;social cognitive theory;Social support;sociodemographics;standard care;standardize measure;Subgroup;Survival Rate;Telephone;Testing;Text Messaging;Time;TNF gene;tool;Training;trial enrollment;United States;Universities;Vegetables;wearable device;Woman;women versus men

PROJECT_TITLE: Optimization of a remote intervention to improve nutrition and physical activity in colorectal cancer survivors

STUDY_SECTION: PRDP

STUDY_SECTION_NAME: Psychosocial Risk and Disease Prevention Study Section[PRDP]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Lung;Lung Cancer;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE Despite recent advances, lung cancer five-year survival rates remain dismal. One barrier to progress is the identification of new treatment strategies for specific genotype-defined subsets of lung cancer. In this work, we characterize the mechanism of a little-studied new cancer oncogene, RIT1, and test two new therapeutic strategies for the treatment of RIT1-mutant lung cancer.

PI_NAMEs: BERGER, ALICE  (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: Antimitotic Agents;aurora kinase;aurora kinase A;Biochemical;Biological;BRAF gene;cancer cell;Cancer cell line;cancer subtypes;cancer therapy;Cells;Chromosomal Rearrangement;clinical practice;Clinical Trials;Complex;Coupled;CRISPR screen;Data;Development;Disease;driver mutation;Drug resistance;Drug Screening;efficacy testing;Epidermal Growth Factor Receptor;Epithelial Cells;Event;experimental study;Family;FDA approved;functional genomics;gain of function mutation;Genes;Genetic;Genetically Engineered Mouse;genome-wide;Genomics;Genotype;Germ Lines;Goals;Human;Impairment;improved;improved outcome;Individual;inhibitor;insight;kinase inhibitor;KRAS2 gene;Laboratories;Lung;Lung Adenocarcinoma;lung cancer cell;Lung Neoplasms;lung tumorigenesis;Malignant neoplasm of lung;Malignant Neoplasms;Maps;Mediating;metaplastic cell transformation;Mitotic Checkpoint;Molecular;Monomeric GTP-Binding Proteins;mutant;Mutate;Mutation;Myeloid Leukemia;Nature;Noonan Syndrome;novel;novel therapeutic intervention;novel therapeutics;Oncogenes;Oncogenic;overexpression;Pathogenicity;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Pattern;Play;Postdoctoral Fellow;pre-clinical;precision oncology;Precision therapeutics;preclinical study;protein complex;Proteins;Proteomics;ras Proteins;Receptor Protein-Tyrosine Kinases;Regulation;Resistance;Role;Signal Transduction;small molecule;Structure;Survival Rate;synergism;targeted treatment;Testing;The Cancer Genome Atlas;Therapeutic;Translating;translational potential;Translations;treatment strategy;tumor;tumorigenesis;tumorigenic;United States;Variant;Work

PROJECT_TITLE: Understanding and exploiting novel therapeutic vulnerabilities of RIT1-driven lung cancer

STUDY_SECTION: MONC

STUDY_SECTION_NAME: Molecular Oncogenesis Study Section[MONC]


ORG_CITY: IRVINE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE. A current challenge in cancer research is understanding tumor heterogeneity, a major cause of resistance to chemotherapy drugs as well as metastasis development. APOBEC3A and APOBEC3B have been identified as two of the major drivers of tumor heterogeneity by promoting the deamination of cytosine to uracil on DNA and inducing genomic mutations. The goal of this proposal is to uncover the molecular mechanisms that govern APOBEC3A and APOBEC3B regulation in cancer cells.

PI_NAMEs: BUISSON, REMI  (contact)

PROGRAM_OFFICER_NAME: OKANO, PAUL

PROJECT_TERMS: anti-cancer research;apoB mRNA editing catalytic subunit;Attenuated;Automobile Driving;Binding;cancer cell;cancer cell differentiation;cancer genome;cancer type;Cells;Cessation of life;chemotherapy;Clinical;Clinical Treatment;Complex;Cytosine;Data;Deamination;Development;Disease Progression;DNA;DNA biosynthesis;DNA Damage;DNA Repair;DNA Sequence Alteration;Drug resistance;Event;Evolution;Family;fighting;Genetic Transcription;Genetic Variation;Genome;Genomic Instability;genomic signature;Genomics;Goals;Heterogeneity;Individual;Induced Mutation;insight;Knowledge;Lead;Location;Malignant Neoplasms;member;Molecular;Mutagenesis;Mutation;Natural Immunity;Neoplasm Metastasis;neoplastic cell;next generation sequencing;Normal Cell;Outcome;Pathway interactions;Patients;Pattern;Pharmaceutical Preparations;Population;prevent;Process;Prognosis;protein complex;Proteins;Regulation;replication stress;Research;Resistance;Sampling;Signal Pathway;Signal Transduction;Single Stranded DNA Virus;Single-Stranded DNA;Site;Source;Stat2 protein;Stress;Survival Rate;System;Technology;Therapeutic;therapeutic development;tumor;tumor heterogeneity;Uracil;Virus Replication;Writing

PROJECT_TITLE: Molecular Mechanisms of APOBEC-Induced Mutagenesis in Cancer

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;HPV and/or Cervical Cancer Vaccines;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Immunization;Infectious Diseases;Pediatric;Prevention;Primary Health Care;Rural Health;Sexually Transmitted Infections;Social Determinants of Health;Vaccine Related

ORG_CITY: HERSHEY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

ORG_STATE: PA

PHR: Project narrative Our proposed research is to evaluate the effectiveness of using an existing implementation strategy infrastructure at academic centers in delivering best-practice communication interventions to increase HPV vaccination rates in rural primary care clinics. The project is relevant to public health because it aims to increase HPV vaccination rates and reduce cancer inequities in rural populations by addressing the context- specific communication needs of both rural providers and parents, especially those parents who are vaccine hesitant. The proposed research is relevant to the NCI because it aims to improve implementation of effective interventions that are responsive to behavioral and sociocultural factors in cancer prevention among rural populations, an understudied area in cancer prevention research.

PI_NAMEs: CALO, WILLIAM ALEXIS (contact)

PROGRAM_OFFICER_NAME: KOBRIN, SARAH

PROJECT_TERMS: 17 year old;Address;Adolescent;Adoption;Age;Area;arm;Behavioral;boys;cancer prevention;care outcomes;Caring;Case Management;Clinic;Clinic Visits;Clinical;Cluster randomized trial;Communication;Community Healthcare;Community Networks;comparison control;comparison intervention;Complex;Consolidated Framework for Implementation Research;cost;Data;Decision Making;design;Dose;effective intervention;Effectiveness;effectiveness evaluation;effectiveness testing;Electronic Health Record;Evaluation;evidence base;experience;Exposure to;Family Practice;follow-up;girls;Goals;health inequalities;Healthcare;HPV vaccine acceptance;Human papilloma virus infection;Human Papilloma Virus Vaccination;Human Papilloma Virus Vaccine;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;implementation framework;implementation outcomes;implementation strategy;improved;Inequity;Infrastructure;innovation;Intervention;Interview;Malignant Neoplasms;men;Methods;Modeling;Monitor;Notification;Outcome;Parents;Penetration;Pennsylvania;Physicians;post intervention;President's Cancer Panel;prevent;Prevention Research;primary care clinic;primary care practice;primary care provider;primary outcome;Provider;Public Health;Randomized;Recommendation;Reporting;Research;Research Personnel;Resources;Risk;Rural;rural America;Rural Community;rural health clinic;Rural Population;Schedule;Scientist;secondary outcome;sex;social media;sociocultural determinant;Source;Structure;Surveys;System;Testing;Time;Training;treatment arm;Use Effectiveness;Vaccination;vaccine hesitancy;Vaccines;video session;Woman;Work

PROJECT_TITLE: HPV ECHO: Increasing the adoption of evidence-based communication strategies for HPV vaccination in rural primary care practices

STUDY_SECTION: DIRH

STUDY_SECTION_NAME: Dissemination and Implementation Research in Health Study Section[DIRH]


NIH_SPENDING_CATS: Biotechnology;Cancer;Dental, Oral, and Craniofacial Disease;Immunotherapy;Orphan Drug;Rare Diseases

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative When developing new cancer treatments, many scientists use animal models in which human tumors are implanted into research animals (i.e. patient-derived xenografts or PDXs). Despite the popularity of these models, we lack understanding of how we bias our results based on the methods we use to make new PDXs (e.g. implanting tumor pieces under the skin of immunocompromised mice as opposed to implanting into the site of origin). To improve the efficiency of pre-clinical research, this proposal will provide a clear answer to this question in head and neck cancer by methodically studying the site of implant, the age of the tumor, and the influence of an immune system on the tumor biology, evolution, and treatment response.

PI_NAMEs: KIMPLE, RANDALL J. (contact)

PROJECT_TERMS: Address;Affect;Age;Animal Experimentation;Animal Model;Animals;anti-cancer treatment;Biological;Biological Models;Biology;Cancer Model;cancer therapy;Caring;Cetuximab;Clinical;Clinical Trials;cost;Data;Decision Making;DNA sequencing;Evolution;expectation;experience;Funding;Generations;Genetic;Genetic Variation;Goals;Head and Neck Cancer;head and neck cancer patient;Histologic;HPV positive;HPV-negative head and neck cancer;Human;Human Biology;human disease;human model;humanized mouse;Immune;immune cell infiltrate;Immune system;Immunocompetent;Immunocompromised Host;Immunotherapy;Implant;implantation;improved;improved outcome;In Situ;In Vitro;innovation;Longevity;Malignant Neoplasms;Methodology;Methods;Modeling;Molecular;mouse model;Mus;Nose;novel;novel therapeutics;Operative Surgical Procedures;Oral;Organoids;Outcome;Pathway interactions;Patient Care;patient derived xenograft model;patient response;Patients;Pharyngeal structure;pre-clinical;pre-clinical research;prevent;Primary Neoplasm;Research;Resistance;response;Role;Sampling;Scientist;Serial Passage;Signal Pathway;single-cell RNA sequencing;Site;Skin;Source;Specimen;Squamous cell carcinoma;Squamous Epithelium;standard care;subcutaneous;Subcutaneous Tissue;targeted treatment;Testing;Therapeutic Studies;therapy resistant;Time;Translating;translational model;treatment response;tumor;Tumor Biology;tumor microenvironment;tumor-immune system interactions;Use Effectiveness;Wisconsin

PROJECT_TITLE: Improving the translational value of head and neck cancer patient-in-mouse models

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


PHR: PROJECT NARRATIVE The resistance to current AR targeted therapies is one of the biggest challenges when treating advanced prostate cancer and largely hinders the clinical outcome of patients with this deadly disease. This study aims to determine the molecular role of a new potential tumor suppressor in prostate cancer, SYNCRIP, in suppressing APOBEC- mediating mutagenesis and resistance to AR targeted therapies. Elucidating the role of this protein and the molecular mechanism of the resistance may identify new actionable targets and establish a pathway for the development of therapeutic approaches to overcome the resistance and ultimately benefit patients.

PI_NAMEs: MU, PING  (contact)

PROGRAM_OFFICER_NAME: KAI, MIHOKO

PROJECT_TERMS: advanced prostate cancer;Affect;American;androgen independent prostate cancer;apoB mRNA editing catalytic subunit;Apoptosis;Automobile Driving;Binding;cancer diagnosis;cancer initiation;Cancer Patient;Castration;Cell Proliferation;Cells;Clinical;Cytoplasm;Data;Deaminase;Dependence;Disease;DNA;DNA Sequence Alteration;enzalutamide;Genes;genetic testing;Genetically Engineered Mouse;Genomics;Human;Impairment;improved;In Vitro;in vitro Model;in vivo;insight;knock-down;Knock-out;Libraries;Malignant neoplasm of prostate;Mediating;men;Messenger RNA;Molecular;mouse model;Mus;Mutagenesis;Mutate;neoplastic cell;novel;Oncogenes;Oncogenic;Organoids;Outcome;Pathologic;Pathway interactions;Patient-Focused Outcomes;Patients;Pattern;prostate cancer cell;prostate cancer cell line;prostate cancer model;Proteins;Reporting;Resistance;resistance mechanism;Resolution;response;RNA-Protein Interaction;Role;screening;senescence;Signal Pathway;synaptotagmin;targeted treatment;therapeutic development;therapeutic target;therapy resistant;treatment response;tumor;tumor growth;tumor heterogeneity;Tumor Suppressor Genes;Tumor Suppressor Proteins;tumorigenesis;Work;Xenograft Model

PROJECT_TITLE: Elucidating the Molecular Role of SYNCRIP in Prostate Cancer and AR Targeted Therapy Resistance

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Immunotherapy;Liver Disease;Skin Cancer

PHR: PROJECT NARRATIVE Melanoma is an aggressive cancer with an increasing incidence. Metastatic melanoma to the liver is frequent and associated with poor prognosis and resistance to novel therapies, such as immunotherapies. The current study will use novel models, methodologies and a large cohort of patient biopsies to elucidate the molecular underpinnings of the development of liver metastasis and how these lesions confer resistance to immunotherapies. This will inform rationale design of novel therapeutic avenues for patients with metastatic melanoma to the liver.

PI_NAMEs: IZAR, BENJAMIN  (contact)

PROJECT_TERMS: advanced disease;Animals;Antibodies;Biological Markers;Biopsy;Brain;cancer cell;cancer immunotherapy;CD4 Positive T Lymphocytes;CD8B1 gene;cell motility;Cell Physiology;cell type;Cells;Cellular Metabolic Process;Clinical;cohort;Communities;CRISPR screen;CRISPR/Cas technology;Dependence;design;Development;Disease;Disseminated Malignant Neoplasm;Drug Design;drug development;Drug resistance;Environment;exome;experimental study;Flow Cytometry;Frequencies;Functional disorder;gene product;Genetic;Genome engineering;Genomics;Glucose;Goals;Hematogenous;Human;Image;Immune;immune cell infiltrate;Immune checkpoint inhibitor;Immune System Diseases;Immunotherapy;Impairment;improved;in vivo;Incidence;inhibitor;innovation;Insulin;Insulin Receptor;insulin signaling;Knock-out;Lesion;Liver;liver biopsy;liver development;Lung;lymph nodes;Lymphatic;Malignant Neoplasms;Measurement;Mediating;Melanoma;Melanoma Cell;Melanoma patient;metabolomics;Metastatic Melanoma;Metastatic Neoplasm to the Liver;Metastatic Neoplasm to the Lung;Methodology;Methods;Modeling;Molecular;mouse model;multiplexed imaging;Mus;Mutation;Neoplasm Metastasis;neoplasm resource;novel;novel therapeutics;Organ;Pancreas;Pathway interactions;Patients;Pattern;Peripheral Blood Mononuclear Cell;Persons;Pharmaceutical Preparations;Pharmacotherapy;phosphoproteomics;Phosphorylation;Physiological;PI3K/AKT;PIK3CG gene;Population;Pre-Clinical Model;Primary Neoplasm;Prognosis;Proto-Oncogene Proteins c-akt;Research;Resistance;response;Role;Route;sample collection;Signal Transduction;single cell sequencing;single-cell RNA sequencing;Site;Survival Rate;T-Lymphocyte;Testing;transcriptomics;treatment response;tumor growth;Variant;Xenograft Model

PROJECT_TITLE: Mechanisms of liver metastasis and associated resistance to immunotherapy

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: RALEIGH

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

ORG_STATE: NC

PHR: PROJECT NARRATIVE CAR-T cell therapy drafts a patient's immune system (cytotoxic T cells) to target and kill tumors and its combination of pin-point specificity and broad efficacy has translated into exciting clinical data and revolutionary treatment for certain blood cancers. The major impediment to widespread use of CAR-T therapy remains its cost, which approaches $500K, a slow manufacturing process and huge regulatory hurdles for facilities that manufacture CAR-T cells. We will develop biomaterial approaches to CAR-T cell therapy, including improved methods to reprogram cells, to release cells quickly to tumors, and even to generate the CAR-T cells entirely within a patient's own body.

PI_NAMEs: BRUDNO, YEVGENY  (contact)

PROGRAM_OFFICER_NAME: SALOMON, RACHELLE

PROJECT_TERMS: 3-Dimensional;Achievement;Adopted;Alginates;Allogenic;Antibodies;Architecture;Autologous;B lymphoid malignancy;Biocompatible Materials;Biological Assay;biomaterial compatibility;bioscaffold;CAR T cell therapy;CD28 gene;CD3 Antigens;Cell Count;Cell Differentiation process;Cell Physiology;Cell Reprogramming;Cell Therapy;Cells;Cellular biology;cellular transduction;Centrifugation;Characteristics;chimeric antigen receptor;chimeric antigen receptor T cells;Circulation;Clinical;Clinical Data;clinically relevant;Coculture Techniques;confocal imaging;cost;crosslink;CXCL10 gene;cytokine;Cytotoxic T-Lymphocytes;Data;density;design;Devices;Disease;Dose;Drug Delivery Systems;Encapsulated;Engineering;Engraftment;Ensure;Generations;Genetic;Goals;graft vs host disease;Hematopoietic Neoplasms;Immune system;immunogenicity;Implant;implantation;improved;In Situ;In Vitro;in vivo;Interleukin-2;Interleukins;Kinetics;Lentivirus;Lentivirus Vector;Longevity;Lymphocyte;Lymphoma;manufacture;manufacturing facility;manufacturing process;mechanical properties;Mediating;Medical;Methods;Modeling;multidisciplinary;Mus;Patients;Peripheral Blood Mononuclear Cell;Phenotype;Physiological;Polybrene;Porosity;preclinical efficacy;prevent;procedure cost;Procedures;Process;Production;programs;Proliferating;Proteins;Protocols documentation;recruit;Research;response;Retroviral Vector;scaffold;Signal Transduction;Solid Neoplasm;Specialist;Specificity;success;System;T-Cell Activation;T-Lymphocyte;Technology;Testing;Therapeutic;Time;transduction efficiency;Translating;translational potential;tumor;Tumor Burden;Viral;Viral Vector;Xenograft Model

PROJECT_TITLE: Biomaterial Scaffolds for Ex Vivo and In Situ CAR-T Cell Production

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


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

ORG_CITY: Aurora

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE  PARP inhibitor resistance is a growing clinical problem, and alternative therapeutic strategies are needed. Hyperactivation of Wnt/beta-catenin signaling drives PARP inhibitor resistance and immune evasion. Thus, we hypothesize that combining a Wnt inhibitor with a checkpoint blockade (e.g., anti-PD-1) could overcome PARPi resistance and activate an anti-tumor immune response. In our unique PARP inhibitor- resistant models, we propose to examine the anti-tumor effect of a first-in-class Wnt/ beta-catenin inhibitor in a syngeneic and humanized mouse models.

PI_NAMEs: BITLER, BENJAMIN G (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: alpha catenin;Anti-Inflammatory Agents;anti-PD-1;anti-tumor immune response;antitumor effect;Attenuated;B-Lymphocytes;beta catenin;Biological Markers;Biological Models;Biological Sciences;brca gene;Cancer Biology;cancer cell;Cancer cell line;cancer infiltrating T cells;Cancer Model;cancer type;CD8-Positive T-Lymphocytes;Cell Communication;Cell Death;Cell Line;Cells;Cessation of life;chromatin immunoprecipitation;Clinic;Clinical;Clinical Management;Clinical Trials;Collaborations;Colorado;comparison control;Complement Factor D;CSF2 gene;cytokine;Data;Detection;differential expression;Disease Resistance;DNA Repair;Down-Regulation;Effectiveness;effector T cell;efficacy testing;Engraftment;Environment;Enzyme-Linked Immunosorbent Assay;Epithelial ovarian cancer;Future;Genes;Genetic;Genetic Transcription;Goals;homologous recombination;humanized mouse;IL6 gene;Immune;immune activation;immune cell infiltrate;immune checkpoint;immune checkpoint blockade;immune checkpoint blockers;Immune Evasion;Immune signaling;immunogenic;Immunosuppression;Immunotherapy;improved;In Vitro;in vivo Model;Inflammation;Inflammatory;inhibitor;innovation;Interferons;Investigation;IRF1 gene;knock-down;Literature;Macrophage;Macrophage Activation;Malignant neoplasm of ovary;Measures;Mediating;Modeling;mouse model;mutant;Mutate;novel;novel therapeutics;Ovarian Serous Adenocarcinoma;overexpression;paracrine;Paracrine Communication;Pathway interactions;patient derived xenograft model;Patients;PD-1/PD-L1;pharmacologic;Poly(ADP-ribose) Polymerase Inhibitor;pre-clinical;Prognosis;programmed cell death ligand 1;Progression-Free Survivals;Proteins;Publishing;Recurrence;refractory cancer;Regulation;Regulatory T-Lymphocyte;Research Personnel;Resistance;response;Role;Serous;Serum;Signal Transduction;success;T cell differentiation;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;therapy resistant;TNF gene;tumor;Tumor Immunity;Tumor Promotion;Tumor Suppressor Proteins;tumor-immune system interactions;Universities;Up-Regulation;WNT Signaling Pathway;Work;Xenograft Model

PROJECT_TITLE: Targeting Wnt signaling in therapy-resistant ovarian cancer


ADMINISTERING_IC: OD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Endocrine Disruptors;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Nutrition;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: PHILADELPHIA

ORG_NAME: DREXEL UNIVERSITY

PHR: NARRATIVE No U.S. cohort to date has evaluated associations with per- and polyfluoroalkyl substances (PFAS) with measures of health consequence of reduced immune function including common childhood infections and some allergies, despite the use of decreased antibody response following vaccine as a critical endpoint for the regulation of PFAS. We propose to combine pediatric birth cohorts with available prenatal PFAS serum concentrations from across the Environmental Influences on Child Health Outcomes cohort, to evaluate associations with childhood infections (bronchiolitis, croup, pneumonia and bronchitis, ear infections) and allergies (allergy symptoms, and atopic dermatitis) at infancy and early childhood for individual PFAS and mixtures. Additional analyses will include effect modification by biological and sociodemographic factors to evaluate the cumulative impact of environmental stressors, as well as study of dietary and sociodemographic determinants of low-level PFAS exposure to develop guidance for reducing exposure among pregnant women in the U.S.

PI_NAMEs: GLEASON, JESSIE  (contact)

PROGRAM_OFFICER_NAME: MASH, CLAY

PROJECT_TERMS: Allergic;Allergic rhinitis;Animals;Antibody Response;Atopic Dermatitis;Awareness;Biological;Birth;Body Burden;Body mass index;Breast Feeding;Bronchiolitis;Bronchitis;Characteristics;Child;Child Health;Childhood;cohort;Cohort Studies;comparative;Croup;Data;data de-identification;design;Diet;dietary;Dietary Questionnaires;drinking water;ear infection;early childhood;Environment;Environmental Impact;environmental stressor;Epidemiology;Ethnic Origin;Evaluation;Exposure to;Frequencies;Future;General Population;Geography;hazard;Health;health determinants;Human;Hypersensitivity;Immune;immune function;Income;Individual;infancy;Infant;Infection;Insurance;interest;International;Level of Evidence;Life;Linear Regressions;Logistic Regressions;manufacture;Measurement;Measures;Modeling;Modification;National Toxicology Program;Outcome;Pediatric cohort;Persons;Pneumonia;Poly-fluoroalkyl substances;Population Heterogeneity;Poverty;Pregnant Women;prenatal;programs;prospective;Prospective Studies;Public Health;Race;Regulation;Research;resilience;Risk;Serum;Severities;sex;Sinus;sociodemographic factors;sociodemographics;Source;Subgroup;Symptoms;systematic review;Toxic effect;Toxicology;Vaccines;virtual;Vulnerable Populations

PROJECT_TITLE: Prenatal per- and polyfluoroalkyl substances (PFAS) exposure and associations with common childhood infections and allergies: A study of risks and resiliencies in the ECHO Program

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 EPH-F (50)]


ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE The proposed studies will establish novel bioengineered ribonucleic acid molecules made through in vivo fermentation production as first-in-class tools for research and development, minimally an addition to conventional agents synthesized in vitro. The lead ribonucleic acids may be used to modulate human lung cancer cell metabolism and immune checkpoint to improve the treatment of lethal lung cancer.

PI_NAMEs: YU, AIMING  (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: Abbreviations;Action Potentials;Amino Acids;Animal Model;Bioinformatics;Biological;Biological Response Modifiers;Biomedical Engineering;Blood;Cancer Cell Growth;Cancer cell line;Cancer Etiology;Carbon;Cell model;Cell Physiology;Cell Proliferation;Cell Survival;Cells;Cessation of life;clinically relevant;comparative efficacy;Development;Drug Combinations;Drug Kinetics;Drug or chemical Tissue Distribution;Effectiveness;efficacy evaluation;Endotoxins;Engineering;Enzymes;Exhibits;Fermentation;Folic Acid;Gene Expression;Gene Expression Regulation;Genetic Transcription;Genome;Goals;Hepatic;High Pressure Liquid Chromatography;HLA Antigens;Human;Immune;immune checkpoint;Immunity;immunogenic;improved;In Vitro;in vivo;innovation;Invaded;invention;Isotopes;Kidney;Knowledge;Lead;Legal patent;Liposomes;Location;lung cancer cell;Malignant neoplasm of lung;Malignant Neoplasms;men;Metabolic;Metabolism;metabolome;MicroRNAs;Mitochondria;Modeling;Modification;Molecular;mouse model;nanocomplexes;nanotherapeutic;Neoplasm Metastasis;Non-Small-Cell Lung Carcinoma;novel;novel therapeutic intervention;Nutrient;Oncolytic;patient derived xenograft model;Pemetrexed;Peptides;Peripheral Blood Mononuclear Cell;Pharmaceutical Preparations;pharmacodynamic biomarker;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacologic Actions;Platinum;Post-Transcriptional Regulation;posttranscriptional;Process;Production;programmed cell death ligand 1;Proliferating;Property;protein expression;Proteins;Proteomics;Regulation;Regulator Genes;Research;research and development;response;restoration;RNA;RNA Interference;Role;Safety;screening;Seminal;Serum;Side;Small Interfering RNA;Small RNA;Specificity;stemness;synergism;Technology;technology platform;Testing;therapeutic miRNA;therapeutic RNA;therapeutically effective;therapy outcome;tool;Toxic effect;transcriptome sequencing;translational potential;tumor;Tumor Immunity;tumor metabolism;tumor progression;United States;Untranslated RNA;Woman

PROJECT_TITLE: Novel bioengineered microRNA therapeutics for lung cancer

STUDY_SECTION: DMPC

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology C Study Section[DMPC]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Childhood Leukemia;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on genetic and epigenetic factors that underlie the etiology of Ph-like acute lymphoblastic leukemia where there exists a cancer health disparity within the Hispanic/Latino population regarding incidence, prevalence, and mortality. Further understanding of these factors lays the groundwork for predictive diagnostics and personalized preventative medicine. Thus, this proposal is relevant to the part of the NIH’s mission to foster discoveries pertaining to the causes, diagnosis, and prevention human diseases and improve human health.

PI_NAMEs: PANNUNZIO, NICHOLAS  (contact)

PROJECT_TERMS: activation-induced cytidine deaminase;Acute Lymphocytic Leukemia;Address;Adolescent and Young Adult;Advocate;Affect;Automobile Driving;B lymphoid malignancy;B-Cell Acute Lymphoblastic Leukemia;B-Lymphocytes;bcr-abl Fusion Proteins;Biological Assay;bisulfite sequencing;California;cancer health disparity;cancer risk;Catchment Area;Cells;Chromosomal translocation;Clinical;Collecting Cell;Communities;community living;Comparative Study;Comprehensive Cancer Center;CRISPR/Cas technology;Cytokine Receptors;Cytosine;Data;Deamination;Death Rate;Diagnosis;Diagnostic;digital;Disease;Disease remission;Disparity;DNA Double Strand Break;DNA Methylation;DNA Repair;Doxycycline;Early Diagnosis;Early Intervention;effective therapy;Enzyme Activation;Epigenetic Process;Ethnic Origin;Etiology;experimental study;Fostering;Gene Expression Profile;General Population;Genes;Genetic;Genome;genome-wide;Genomic Instability;Genomics;Goals;Health;health disparity;Heavy-Chain Immunoglobulins;high risk;Hispanic;hispanic community;Hispanic Populations;Human;human disease;IGH@ gene cluster;imprint;improved;improved outcome;Incidence;individualized prevention;innovation;Knowledge;Latino Population;lectures;lentiviral integration;Link;Maps;meetings;Methods;Methylation;methylation pattern;Mission;Modification;Molecular;mortality;Mutation;Not Hispanic or Latino;novel;novel diagnostics;Oncogenes;overexpression;Patients;personalized medicine;personalized predictions;Philadelphia Chromosome;Population;predictive marker;Predisposing Factor;Prevalence;Prevention;Prevention strategy;Preventive Medicine;Process;Public Health;Recurrent disease;Regulation;relapse risk;repaired;Research;Risk;Role;Sampling Studies;Site;stem;Survival Rate;Techniques;Testing;Time;treatment comparison;treatment response;United States National Institutes of Health;Whole Blood;Work

PROJECT_TITLE: Defining the Mechanism of Genome Rearrangements in Ph-Like ALL to Determine Predictive Markers in High-Risk Hispanic Populations

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


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_DEPT: SURGERY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Relevance narrative Approximately 19% of the US population resides in rural areas; for over three decades, this population has experienced increasingly inferior health outcomes when compared with their urban counterparts. The underlying cause(s) of the widening rural/urban gap in cancer outcomes is hypothesized to be multifactorial, and this study will provide a comprehensive multi-level evaluation of rural/urban mortality disparities. Findings will provide the critical evidence needed to inform policy, as well as to inform intervention development to address the systemic disparities in mortality experienced by rural patients with cancer.

PI_NAMEs: KENZIK, KELLY  (contact)

PROGRAM_OFFICER_NAME: DELLAVALLE, CURT TAVIS

PROJECT_TERMS: Address;Area;Behavioral Risk Factor Surveillance System;Black Populations;Black race;Budgets;cancer health disparity;Cancer Patient;Caring;Censuses;Characteristics;Clinical Trials;Code;cohort;Commuting;comorbidity;Complex;contextual factors;County;Data;data registry;Data Set;Databases;Death Rate;deprivation;Diagnosis;Disparity;Emergency department visit;Evaluation;evidence base;Excess Mortality;experience;Future;Geographic Factor;Geographic Locations;Geography;Health;Health behavior;Health Information National Trends Survey;Health Insurance;health literacy;Health Services Accessibility;Healthcare;Hospitalization;indexing;Individual;Inferior;Insurance;Intervention;Link;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Mediation;Methodology;Modeling;mortality;mortality disparity;multilevel analysis;Nature;neoplasm registry;Office Management;Outcome;Participant;Play;Policies;Policy Developments;Policy Maker;Population;Poverty;Poverty Areas;primary outcome;Quality of Care;Race;Reasons for Geographic And Racial Differences in Stroke;Reporting;Research Personnel;Role;Rural;rural area;rural disparities;rural patients;Rural Population;rural poverty;rural residence;rurality;Sampling;screening;SEER Program;Social support;social vulnerability;sociodemographics;Socioeconomic Status;Specialist;statistics;Stroke Belt;System;therapy development;Transportation;urban area;urban disparity;urban residence;virtual;Work

PROJECT_TITLE: Understanding rural mortality disparities in cancer: a multi-level approach

STUDY_SECTION: CHSB

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


NIH_SPENDING_CATS: Cancer;Clinical Research;Digestive Diseases;Immunotherapy;Liver Disease;Pancreatic Cancer;Rare Diseases

ORG_DEPT: PATHOLOGY

PHR: PROJECT NARRATIVE Nearly half of patients with pancreatic neuroendocrine tumors (PanNET) present with liver metastases at diagnosis, which correlates with poor prognosis, and the immunosuppressive microenvironment of PanNET limits the efficacy of immune checkpoint inhibitors (ICI) for metastatic PanNET patients, with a less than 10% objective response rate. Emerging evidence suggests that increased vascular leakage and poor vascular perfusion resulting from vascular destabilization impair immune cell infiltration into tumors, thus facilitating tumor immune evasion and consequent tumor progression. In this work, we propose to study role of angiopoietin-2/Tie2 signaling, which regulates vascular destabilization and dysfunction, in liver metastatic progression and in ICI therapy resistance of metastatic PanNET as well as the potential of Tie signaling molecules as sensitive cancer biomarkers for PanNET patients.

PI_NAMEs: KIM, MINAH  (contact)

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: Agonist;Angiopoietin-2;ANGPT2 gene;antagonist;anti-PD1 therapy;Binding;Biological Markers;Blocking Antibodies;Blood Vessels;cancer biomarkers;CD8-Positive T-Lymphocytes;Cell Physiology;checkpoint therapy;Clinical Management;Data;Development;Diagnosis;Disease;Endothelium;Excision;Extravasation;follow-up;Functional disorder;Genetic;Growth;high risk;Human;immune cell infiltrate;Immune checkpoint inhibitor;Immune Evasion;Immunodeficient Mouse;immunoregulation;Immunosuppression;Immunotherapy;Impairment;improved;Incidence;Inflammatory;insight;Islet Cell Tumor;Liver;liver function;Mediating;Metastatic Neoplasm to the Liver;mouse model;Mus;Neoplasm Metastasis;objective response rate;Operative Surgical Procedures;Patients;Perfusion;Plasma;potential biomarker;Primary Neoplasm;Prognosis;prognostic;Prognostic Marker;receptor;Receptor Protein-Tyrosine Kinases;Regulation;Resistance;response;Role;Sampling;Signal Transduction;Signaling Molecule;T cell infiltration;T-Lymphocyte;Testing;Therapeutic;therapeutic target;TIE-2 Receptor;Time;transcriptome sequencing;tumor;tumor diagnosis;Tumor Escape;tumor growth;Tumor Markers;tumor progression;tumor-immune system interactions;Up-Regulation;Vascular remodeling;Work

PROJECT_TITLE: Angiopoietin-2/Tie2 signaling regulation of liver metastasis in pancreatic neuroendocrine tumors

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Cancer Genomics;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Nutrition;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: HONOLULU

ORG_NAME: UNIVERSITY OF HAWAII AT MANOA

ORG_STATE: HI

PHR: This renewal application seeks support for the infrastructure maintenance of the Multiethnic Cohort (MEC) Study, established in 1993-1996, to continue a well-integrated program of research testing innovative hypotheses aimed at ensuring that racial/ethnic disparities are investigated and progress in disease prevention applies to major US racial/ethnic minorities. By including 215,251 men and women mostly of 5 racial/ethnic populations (African Americans, Japanese Americans, Latinos, Native Hawaiians and Whites), the MEC is the most racially and ethnically diverse cancer cohort, and its value for etiologic research on chronic diseases is widely recognized. Leadership of the MEC entails a highly interactive, team-science approach; investigators have amply demonstrated willingness to share data and samples.

PI_NAMEs: HAIMAN, CHRISTOPHER ALAN;LE MARCHAND, LOIC  (contact);WILKENS, LYNNE R

PROGRAM_OFFICER_NAME: MAHABIR, SOMDAT

PROJECT_TERMS: actigraphy;African American population;Aliquot;Anthropometry;Bayesian Modeling;biobank;Biological Markers;Blood;blood product;Blood specimen;Calibration;California;Cancer health equity;Cessation of life;Chemicals;Chronic Disease;climate change;Clinical;cohort;Cohort Studies;complex data;computerized;Computerized Medical Record;Consultations;Cost efficiency;Cryopreservation;Cultural Diversity;Data;Data Analyses;data harmonization;Data Management Resources;Data Security;Data Set;data sharing;database of Genotypes and Phenotypes;Databases;design;Diagnosis;Diagnostic;dietary;Dietary intake;digital repositories;Disease Outcome;disorder prevention;Energy Intake;Energy Metabolism;Ensure;Environment;Environmental Epidemiology;Environmental Exposure;Environmental Risk Factor;Epigenetic Process;epigenomics;ethnic difference;ethnic disparity;ethnic diversity;ethnic health disparity;ethnic minority;Ethnic Origin;Ethnic Population;Etiology;follow-up;Funding;Genetic;genetic risk factor;genome wide association study;Genomics;Genotype;Geographic Locations;Grant;Hawaii;Health;Health behavior;Health equity research;Hospitals;improved;Incidence;indexing;Indirect Calorimetry;Infrastructure;innovation;Intake;Japanese American;Latino Population;Leadership;Life Style;Lymphocyte;Maintenance;Malignant Neoplasms;Measurement;Measures;Medical;Medicare/Medicaid;member;men;metabolomics;Methodology;microbiome research;multi-ethnic;Native Hawaiian;Neighborhoods;neoplasm registry;Normal tissue morphology;novel strategies;nutrition;Oral;Outcome;Paper;Participant;Phenotype;Physical activity;Physiological;Pilot Projects;Planning Techniques;Postdoctoral Fellow;programs;prospective;Prospective, cohort study;Publishing;Questionnaires;Race;racial disparity;racial diversity;racial health disparity;racial minority;racial population;Registries;Research;Research Methodology;Research Personnel;Research Project Grants;Residual state;Resources;Rest;Risk Factors;Saliva;Sampling;Science;Slide;Social Environment;social health determinants;Specimen;stool sample;Structural Racism;Students;Testing;Tissue Banks;Tissue Sample;Training;tumor;tumor registry;Tumor Tissue;United States National Institutes of Health;Urine;Vertebral column;Vital Statistics;web platform;willingness;Woman

PROJECT_TITLE: Understanding Ethnic Differences in Cancer: The Multiethnic Cohort Study

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Uterine Cancer;Women's Health Research

ORG_CITY: DETROIT

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: Project Narrative/Relevance African Americans continue to have poor outcomes after a cancer diagnosis and few African American cohorts exist to support studies of the determinants of cancer prognosis and progression, survival, quality of life and post-treatment outcomes. The proposed continuation of follow-up of this cohort of population-based, African American cancer survivors will provide longer-term outcomes data and biospecimens for a research agenda driven by priorities in the African American community and aimed at understanding and improving cancer outcomes in this population.

PI_NAMEs: BEEBE-DIMMER, JENNIFER L;SCHWARTZ, ANN G. (contact)

PROGRAM_OFFICER_NAME: GALLICCHIO, LISA M

PROJECT_TERMS: actigraphy;Address;Affect;African American;African American population;Aftercare;Age;Aging;Anxiety;Back;Biological;cancer diagnosis;Cancer Etiology;cancer health disparity;Cancer Prognosis;Cancer Survivor;cancer therapy;Caring;Cessation of life;cohort;Collaborations;Colorectal Cancer;Communities;community engagement;Community Outreach;Community Participation;community partners;comorbidity;Complex;COVID-19 impact;Data;Death Rate;Development;Diagnosis;Disease;disparity gap;Early Diagnosis;early onset;Early treatment;end of life care;Endometrial Carcinoma;Enrollment;Ethnic Population;Event;experience;Family;Financial Hardship;financial toxicity;follow-up;Funding;Geography;Goals;Grant;Health;Health behavior;health equity;improved;Incidence;Institution;Investigation;Link;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Measures;Medical;Medical History;Medical Records;member;Mental Depression;metropolitan;mortality;Mutation;Neighborhoods;Not Hispanic or Latino;Outcome;outcome disparities;Paper;participant enrollment;participant retention;patient population;Patients;Periodicals;Population;population based;Population Heterogeneity;primary caregiver;psychologic;Publishing;Quality of life;racial population;Recording of previous events;Recurrence;Recurrent disease;Registries;Reporting;Research;Research Priority;Resources;Second Primary Cancers;side effect;sleep health;sociodemographics;Sociology;Source;Surveys;Survivors;survivorship;System;treatment adherence;Treatment outcome;tumor;tumor progression;United States Centers for Medicare and Medicaid Services;United States National Institutes of Health;Update;Work

PROJECT_TITLE: Detroit Research on Cancer Survivors (Detroit ROCS)


NIH_SPENDING_CATS: Breast Cancer;Cancer;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

PHR: Project Narrative This grant will help elucidate mechanisms of how glycosylation regulates pathways of cancer initiation. Specifically, we will focus on how O-GlcNAcylation regulates tumor-initiation pathways. Additionally, we will test novel agents for their anti-tumor properties thus this proposal may help establish a new therapeutic target for treatment of cancer.

PI_NAMEs: BALL, LAUREN ELIZABETH;REGINATO, MAURICIO J. (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Model;Breast Epithelial Cells;cancer cell;Cancer Control;cancer initiation;Cancer Model;cancer stem cell;cancer therapy;Cell Death;Cell Maintenance;Cell Proliferation;Cells;chemotherapy;conventional therapy;Data;design;detection of nutrient;Disease;Drug resistance;Drug Targeting;endoplasmic reticulum stress;Enzymes;Epithelium;experimental study;Gene Expression Regulation;Glucose;Glutamine;Glycolysis;glycosylation;Goals;Grant;Growth;Hexosamines;In Vitro;in vivo;in vivo Model;inhibitor;Link;Malignant Breast Neoplasm;Malignant Neoplasms;Mammospheres;Metabolic;Metabolic Pathway;Metabolism;Molecular;Natural regeneration;Neoplasm Metastasis;new therapeutic target;novel;Nuclear;Nutrient;O-GlcNAc transferase;overexpression;Oxygen;Pathway interactions;pharmacologic;Phenotype;Play;pre-clinical;Process;Property;prostate cancer cell;Proteins;Radiation therapy;rapid growth;refractory cancer;Regulation;Relapse;Resistance;Role;self-renewal;sensor;Shunt Device;Signal Transduction;stem cell biomarkers;Stem Cell Factor;stem-like cell;Testing;Therapeutic;therapeutic target;therapeutically effective;Time;tumor;tumor growth;tumor initiation

PROJECT_TITLE: Role of O-GlcNAcome on Breast Cancer Initiating Cells


NIH_SPENDING_CATS: Cancer;Clinical Research;Immunotherapy

ORG_CITY: ATLANTA

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

ORG_STATE: GA

PHR: PROJECT NARRATIVE This project investigates the mechanical regulation of binding, signaling, and function of the molecule Programmed cell death 1 (PD-1) in relation to T cell responses to melanoma. Results from this project will advance our understanding of PD-1 mechanobiology and improve cancer immunotherapy by targeting the mechanoregulation of PD-1.

PI_NAMEs: ZHU, CHENG  (contact)

PROGRAM_OFFICER_NAME: JOHNSON, ERIC MICHAEL

PROJECT_TERMS: acute infection;adaptive immunity;Adoptive Cell Transfers;Amino Acids;Antigens;Binding;cancer immunotherapy;Cancer Vaccines;CD28 gene;CD4 Antigens;CD8 receptor;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Differentiation process;cell killing;Cell Physiology;Cells;cellular imaging;chemokine receptor;Chronic;Communicable Diseases;Complex;Coupled;Cytokine Receptors;Cytotoxic T-Lymphocytes;Data;Devices;Discrimination;Disease;Dissociation;DNA;Effector Cell;Engineering;exhaustion;Foundations;Generations;Goals;gp100 Antigen;Human;Image;Immunologist;Immunooncology;Immunotherapy;improved;in silico;In Situ;In Vitro;in vivo;insight;Investigation;Kinetics;Ligands;Major Histocompatibility Complex;Malignant Neoplasms;Mechanics;Mediating;Melanoma;Memory;Methods;Microfluidics;Modeling;Molecular;Molecular Conformation;molecular dynamics;mouse model;multidisciplinary;Mus;Mutate;novel strategies;Oncology;Peptide Receptor;Peptides;physical science;programmed cell death ligand 1;programmed cell death protein 1;receptor;Receptor Signaling;Regulation;Reporting;response;Signal Transduction;single molecule;Solid;stem;stem-like cell;stemness;Structure;synergism;T cell differentiation;T cell response;T cell therapy;T memory cell;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Therapeutic;Thinking;tool;tumor;Tumor Immunity;Vaccination;Vaccine Therapy;Virus Diseases

PROJECT_TITLE: Exploiting the Mechanobiology of PD-1 for Cancer Immunotherapy


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

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative We focus on understanding fundamental mechanisms governing immune modulation and progression of disseminated tumor cells at the metastatic sites, both of which carry immense clinical relevance in treating metastatic disease in women with triple negative breast cancer, for which there currently is no cure. Moreover, the proposed studies focusing on tumor-derived exosomes carry a high translational potential in the development of liquid biopsy-based biomarkers for noninvasive detection, and discovery of new targets for immunotherapy and prevention of metastasis.

PI_NAMEs: GUO, WEI ;RADHAKRISHNAN, RAVI  (contact);WEAVER, VALERIE MARIE

PROGRAM_OFFICER_NAME: NADEAU, CHRISTINE FRANCES

PROJECT_TERMS: Address;Adhesions;Affect;Aggressive behavior;anti-cancer research;Biological Markers;Biology;Biomedical Engineering;biophysical model;Breast Cancer Cell;Breast Cancer Model;Breast Cancer Patient;Cancer Biology;cancer cell;Cancer Patient;cell cortex;Cell Culture Techniques;cell growth;Cells;Cellular biology;Cessation of life;Clinical;Clinical Pathology;clinically relevant;Collaborations;Cytoskeleton;Data;Deposition;Desmoplastic;Development;Devices;Disease;Disseminated Malignant Neoplasm;Drug Kinetics;Exhibits;exosome;experimental study;Extracellular Matrix;Fostering;Foundations;Future;Genetically Engineered Mouse;Immune checkpoint inhibitor;Immune Evasion;Immune system;Immunity;Immunologic Surveillance;Immunology;immunoregulation;Immunosuppression;Immunotherapy;In Vitro;in vivo;insight;interest;Invaded;Isogenic transplantation;Joints;Link;liquid biopsy;Macrophage;Malignant Neoplasms;Mechanics;mechanotransduction;Mediating;Membrane;metastasis prevention;Metastatic/Recurrent;Methods;Modeling;Modification;Molecular;mortality;mouse model;multi-scale modeling;multidisciplinary;Neoplasm Metastasis;neoplastic cell;Non-Invasive Detection;novel;Pathway interactions;Patients;PD-1/PD-L1;pharmacokinetic model;physical science;Play;prevent;Primary Neoplasm;Process;Production;protein transport;Publications;Research;Research Personnel;Resistance;response;Role;Signal Transduction;Site;T-Lymphocyte;Technology;Testing;Therapeutic Intervention;Tissues;trafficking;translational potential;triple-negative invasive breast carcinoma;tumor;Tumor Immunity;tumor immunology;tumor microenvironment;tumor progression;Tumor Promotion;Tumor Tissue;Tumor-Derived;United States;Woman;women's treatment;Xenograft Model;Xenograft procedure

PROJECT_TITLE: A physical sciences approach to investigate the role of exosomes in metastatic progression


NIH_SPENDING_CATS: Biomedical Imaging;Brain Cancer;Brain Disorders;Cancer;Clinical Research;Immunotherapy;Machine Learning and Artificial Intelligence;Neurosciences;Rare Diseases

ORG_CITY: SCOTTSDALE

ORG_NAME: MAYO CLINIC ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Our inability to explain why some patients do not respond to immunotherapy, combined with our inability to predict the responders, poses a serious challenge to advancing cancer care and research. Currently, biopsies serve as the most informative way to assess the immunological activity within a cancerous area, but we are spatially and temporally limited in the number of biopsies we can obtain from patients, especially in cases of brain cancer. We propose here a novel strategy merging artificial intelligence and mechanistic modeling to reveal the spatial and temporal tumor-immune landscape within patients by connecting a unique resource of image-localized biopsies and clinical imaging for cohorts treated with standard and immunotherapies.

PI_NAMEs: CANOLL, PETER ;HU, LELAND ;SWANSON, KRISTIN R (contact)

PROJECT_TERMS: Advanced Malignant Neoplasm;anti-cancer research;Anti-Inflammatory Agents;Area;Artificial Intelligence;Biological;biological heterogeneity;Biophysics;Biopsy;cancer care;Cancerous;cell type;Cells;Classification;Clinical;clinical decision-making;clinical imaging;cohort;Complex;Computer Models;cytotoxic;Data;Decision Making;Diagnostic;Early identification;Edema;effective therapy;Environment;Evolution;Future;Glioblastoma;Glioma;Goals;Heterogeneity;Image;Immune;immune cell infiltrate;Immune system;Immunologics;Immunology;Immunosuppression;Immunotherapy;In Situ;in vivo;Inflammation;Inflammatory;insight;Link;Location;Machine Learning;machine learning model;Macrophage;Magnetic Resonance Imaging;Malignant neoplasm of brain;Malignant Neoplasms;Maps;Measures;Microglia;Modeling;Molecular;molecular phenotype;neoplastic cell;Neuroglia;novel strategies;Oncology;Operative Surgical Procedures;Outcome;outcome prediction;Pathway interactions;Patient-Focused Outcomes;Patients;personalized approach;Phenotype;Physics;Population;predictive modeling;Predisposition;Prognosis;quantitative imaging;radiomics;Recurrence;Resources;response;Role;Scientist;serial imaging;sex;Sex Differences;Signal Transduction;single-cell RNA sequencing;Spatial Distribution;spatiotemporal;Specimen;standard of care;synergism;System;Testing;Therapeutic;Therapeutic Intervention;Time;tool;tumor;tumor behavior;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;tumor-immune system interactions;Variant

PROJECT_TITLE: Image-based models of tumor-immune dynamics in glioblastoma


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Rare Diseases;Skin Cancer

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Project Narrative High throughput sequencing of the rearranged T cell receptor genes (HTS) is an approach that profiles T cells in the tissue and has enhanced the ability to diagnose and manage patients with cutaneous T cell lymphoma (CTCL). However, the formalin used to preserve skin biopsy specimens damages DNA and affects readings in a way that could lead to errors in patient diagnosis and care. We seek to identify new fixatives and tissue handling procedures that enable multiple different analyses to be accurately carried out on small skin biopsies obtained in CTCL clinical trials, including HTS readings, histologic studies and measures of gene expression.

PI_NAMEs: CLARK, RACHAEL ANN (contact)

PROGRAM_OFFICER_NAME: RAO, ABHI

PROJECT_TERMS: Affect;Age;Biological Assay;Biological Markers;Biometry;Biopsy;Biopsy Specimen;Blood;cancer type;Caring;Cell Count;Clinical;Clinical effectiveness;Clinical Trials;Collection;Cutaneous Lymphoma;Cutaneous T-cell lymphoma;Data;Dermatology;Diagnosis;Disease;Disease Progression;disorder risk;DNA;DNA Damage;Epitopes;Fixatives;Formalin;Freezing;Future;Gel;Gene Expression;Genes;Goals;High-Throughput Nucleotide Sequencing;Histologic;histological studies;Histology;Human;Immunology;Immunotherapy;indexing;Industrialization;Industry;innovation;lymph nodes;Malignant - descriptor;Measurement;Measures;next generation;Non-Hodgkin's Lymphoma;Nucleic Acids;Oncology;Pathology;Patients;Performance;phase III trial;Placebo Control;preservation;Procedures;Proteins;Randomized;Reproducibility;resiquimod;response;Reverse Transcriptase Polymerase Chain Reaction;RNA;Sampling;Skin;skin biopsy;skin lesion;Specimen;T cell receptor repertoire sequencing;T-Cell Receptor;T-Cell Receptor Genes;T-Lymphocyte;Techniques;Temperature;Testing;Time;Tissue Banks;tissue processing;Tissues;treatment response;tumor

PROJECT_TITLE: Optimizing pre-analytic sample handling for high throughput TCR sequencing in cutaneous T cell lymphoma


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Liver Cancer;Liver Disease;Rare Diseases

PHR: Project Relevance to Public Health SIGNIFICANCE:  Cancer incidence and mortaility trends show therapeutic progress against multiple liquid and solid tumors, but some solid tumor types such as liver cancer remain exceptions [Siegel 2020], which motivates a deeper understanding of solid tumors.  We hypothesize a causal biophysical link between two aspects of solid tumors that are widely considered unrelated, namely (1) stiffness of the tissue which is a major risk factor for liver cancer – as it is for other maliganancies such as breast cancer, and (2) genetic changes – that are a hallmark of cancer and that are increasingly being targeted in therapy but are also most abundant in solid tumors.  We propose a mechano-genetics process in which genetic changes are caused by tissue stiffness including compression in mitosis, and to test our hypothesis and clarify aspects of mechanism, we will develop and apply a novel approach with gene editing that allows us to see genetic changes in real-time, in single cells under physical duress.

PI_NAMEs: DISCHER, DENNIS E. (contact)

PROJECT_TERMS: 3-Dimensional;Alleles;Biophysics;Biopsy;Brain;cancer cell;cancer imaging;cancer type;Cell Count;Cell division;cell killing;Cell Nucleus;Cell Separation;Cells;chromosome loss;chromosome missegregation;Chromosomes;constriction;Cytoplasm;Defect;DNA;DNA Damage;DNA Repair;DNA sequencing;Engineering;Engraftment;Exhibits;experimental study;Flow Cytometry;Genes;Genetic;Genetic Processes;Goals;Growth;Hematopoietic Neoplasms;Heritability;Human;human induced pluripotent stem cells;Image;Immune checkpoint inhibitor;Immunodeficient Mouse;In Vitro;in vivo;Incidence;Injections;Interphase;intraperitoneal;Karyotype determination procedure;knock-down;Link;Liquid substance;Liver;liver cancer patient;Liver neoplasms;Malignant Breast Neoplasm;Malignant neoplasm of liver;Malignant Neoplasms;Measures;Mechanics;Methods;micronucleus;Mitosis;Mitotic spindle;Modernization;Motility;Mutation;Normal Cell;novel strategies;Nuclear Envelope;Palpable;Pathway interactions;patient derived xenograft model;Patients;Pediatric Neoplasm;Pharmaceutical Preparations;Phenotype;Physics;Point Mutation;pressure;prevent;Process;Public Health;red fluorescent protein;Reporter;Risk Factors;Rupture;Shapes;Site;soft tissue;Soft Tissue Neoplasms;Solid Neoplasm;Sorting;spheroids;Squash;Stress;subcutaneous;Suspensions;Testing;Therapeutic;three dimensional cell culture;Three-Dimensional Imaging;Time;Tissues;trend;tumor;Tumor Suppressor Proteins;Tumor Tissue;tumor xenograft

PROJECT_TITLE: Live cell reporters of genetic changes in stiff vs soft surroundings - Causes & Consequences


NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Estrogen;Genetics;Human Genome;Precision Medicine;Women's Health Research

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

PHR: PROJECT NARRATIVE We will develop a new mechanistic understanding of cancer cell cycle dysregulation and resistance pathways using an experimentally validated mathematical model applied to patient tumor cells. These analyses will provide a guide to personalized treatment combinations and dosing for more durable control of cancer cell proliferation.

PI_NAMEs: NATH, ARITRO  (contact)

PROGRAM_OFFICER_NAME: DUECK, HANNAH RUTH

PROJECT_TERMS: Acceleration;Automobile Driving;Biological Models;Biopsy;Breast Cancer Cell;Breast Cancer Patient;Bypass;cancer cell;Cancer Control;Cancer Patient;CDK4 gene;Cell Cycle;Cell Cycle Checkpoint;Cell Cycle Progression;Cell Cycle Regulation;Cell division;Cell Line;Cell Lineage;Cell Proliferation;cell type;Cells;Cessation of life;Chemosensitization;Clinical;Clinical Trials;Collection;Combined Modality Therapy;Couples;Cyclin-Dependent Kinase Inhibitor;Data;design;Dose;Drug Combinations;Drug Modelings;drug testing;Drug usage;Effectiveness;Endocrine;Equilibrium;ERBB2 gene;ErbB4 gene;Estrogen receptor positive;Estrogens;Evolution;experimental study;Feedback;Gene Expression;Gene Expression Profile;Hand;hormone therapy;improved outcome;In Vitro;in vitro Model;in vivo;inhibitor;kinase inhibitor;Letrozole;Malignant Breast Neoplasm;MAP Kinase Gene;Maps;mathematical model;Measurement;Measures;Mediating;Mitogen-Activated Protein Kinase Kinases;Modeling;neoplastic cell;Outcome Study;Pathway interactions;patient response;Patients;personalized medicine;Pharmaceutical Preparations;Pharmacotherapy;Phosphotransferases;Population;Preoperative Endocrine Therapy;prevent;Proliferating;promoter;reconstruction;refractory cancer;Repression;Resistance;resistance mechanism;response;Role;Sampling;Series;Signal Pathway;Signal Transduction;single-cell RNA sequencing;spheroids;System;targeted treatment;Testing;Therapeutic;therapy resistant;Time;tool;transcriptomics;treatment strategy;tumor;tumor heterogeneity;Tumor stage;Up-Regulation

PROJECT_TITLE: Mechanism of estrogen independent proliferation in ER+ breast cancer cells


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Complementary and Integrative Health;Genetics;Infectious Diseases;Natural Products

ORG_CITY: UNIVERSITY

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MISSISSIPPI

ORG_STATE: MS

PHR: Project Narrative Myxobacteria are an incredible resource for discovery of bacterial natural products and have provided candidate therapeutics with antibacterial, antifungal, cytotoxic, antiviral, and immunosuppressive activities. However, established synthetic biology tools for investigation of myxobacteria pale in comparison with techniques available for routine use with other prolific producers of biologically active metabolites such as Streptomyces. The proposed research will develop and utilize novel synthetic biology tools to ensure continued natural products discovery from this unique and underexplored resource.

PI_NAMEs: STEVENS, DAVID COLE (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Actinobacteria class;Anti-Bacterial Agents;anti-fungal agents;Anti-viral Agents;Bacteria;Bacterial natural products;Biological Models;Chemicals;Clinical Pharmacology;Collection;comparative;contig;cytotoxic;Data;Development;DNA;drug discovery;Engineering;Ensure;Environment;Escherichia coli;Evolution;experimental study;Future;Gene Cluster;General Practitioners;Genetic;genetic association;Genetic Recombination;Genome;genome sequencing;Gifts;Green Fluorescent Proteins;Health;Horizontal Gene Transfer;Human;Immunosuppression;Immunosuppressive Agents;improved;innovation;Investigation;Life Style;Location;Maintenance;Methodology;Methods;Microbe;microbial host;Mining;Modeling;Molecular;Monitor;Myxococcales;Myxococcus xanthus;Natural Increases;Natural product discovery;Natural Products;Nature;novel;novel strategies;novel therapeutics;Nutrient;Phenotype;Plasmids;Predatory Behavior;preservation;pressure;Process;Production;Reporter;Research;Resistance;Resources;response;scaffold;Source;Streptomyces;success;synthetic biology;System;Techniques;Therapeutic;therapeutic candidate;tool;Viral Physiology

PROJECT_TITLE: Expansion and application of synthetic biology tools for natural products discovery from myxobacteria

STUDY_SECTION: CSB

STUDY_SECTION_NAME: Chemical Synthesis and Biosynthesis Study Section[CSB]


ORG_CITY: BUFFALO

ORG_NAME: ROSWELL PARK CANCER INSTITUTE CORP

PHR: PROJECT NARRATIVE The long-standing history and contribution to the Human Genome Program through clone generation (RP11 BAC libraries), high throughput mapping, array technology development, and distribution of these resources worldwide, provides a track record documenting expertise of the Genomics Shared Resource (GSR), which is an integral part of the Roswell Park Comprehensive Cancer Center (Roswell Park) Cancer Center Support Grant (CCSG) program (P30CA016056, PI Dr. Candace Johnson). As the Director of the GSR with over 19 years of relevant experience, Dr. Prashant Singh’s efforts are dedicated to support the mission of the GSR, which is to provide state-of-the-art instrumentation and expertise that enables CCSG members to acquire and analyze genomic data sets across basic, translational, clinical and population studies. Dr. Singh’s intellectual and practical contributions are invaluable to NCI-funded projects of the CCSG program members. Funding Dr. Singh as an NCI Core-based Scientist will ensure the stability and continued growth of a vital resource to Roswell Park’s CCSG programs and allow him to dedicate his time for novel technology development.

PI_NAMEs: SINGH, PRASHANT KUMAR (contact)

PROGRAM_OFFICER_NAME: MCKEE, TAWNYA C

PROJECT_TERMS: anti-cancer research;Applications Grants;Award;Bacterial Artificial Chromosomes;Biological Assay;Cancer Center Support Grant;cancer genetics;cancer genomics;Cancer Patient;cancer research center director;Clinical;Clinical Research;Clinical Trials;Complement;Comprehensive Cancer Center;Data;Dedications;design;Diagnostic;Doctor of Philosophy;Ensure;epigenomics;experience;Faculty;Funding;Generations;genetic makeup;Genomic approach;genomic data;Genomics;Genomics Shared Resource;Goals;Grant;Growth;Human Genome;Institution;instrumentation;Leadership;Libraries;Malignant Neoplasms;Maps;meetings;member;Mission;NCI Center for Cancer Research;new technology;New York;Ovarian;Peer Review;personalized medicine;Play;population based;Population Study;Preparation;Principal Investigator;professor;Program Research Project Grants;programs;Publications;Recording of previous events;recruit;Reporting;Research;research clinical testing;Research Support;Resources;Role;Sampling;Science;Scientist;Services;success;technology development;Time;tobacco flavor;tobacco products;translational study;United States National Institutes of Health;Wages;Work

PROJECT_TITLE: Director Genomics Shared Resource

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-1 (M2)]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: Project Narrative Metabolic relationships between the retina and RPE are essential for retina function and survival. We will use measurements of metabolic flux to determine how those metabolic relationships function within an eye.

PI_NAMEs: HURLEY, JAMES BRYANT (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: Affect;Animals;Biochemical;Blood Glucose;Catheters;Cause of Death;Cells;Characteristics;Choroid;Collaborations;Communities;Consumption;Cultured Cells;design;Ecosystem;Energy Metabolism;Enzymes;experimental study;Eye;Fructose;Genes;Glucose;glucose transport;glucose uptake;Glycogen;Glycolysis;Hypoxia Inducible Factor;in vivo;Label;Measurement;Measures;Metabolic;Metabolism;Methods;Modeling;mouse model;Muller's cell;Mus;Mutation;oxidative damage;Pentosephosphate Pathway;photoreceptor degeneration;prevent;Pyruvate Kinase;response;Retina;Retinal Degeneration;Rod;SLC2A1 gene;Structure of jugular vein;Testing;Therapeutic;Tissues;Vertebrate Photoreceptors;Vision

PROJECT_TITLE: Determinants of Rod and Cone Response Characteristics

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: PROJECT NARRATIVE Tyrosine kinase driven Non-small-cell lung cancers (NSCLC) develop resistance to tyrosine kinase inhibitors. Waiting for resistance, reverse engineering its molecular origins, and then responding to that resistance with new drugs is a slow, costly, and ultimately losing battle. This grant will propel the model driven forward engineering design of “dual-switch selection drives” in NSCLC that re-program tumor cells to work with existing therapies to combat drug resistance—regardless of molecular origin.

PI_NAMEs: PRITCHARD, JUSTIN  (contact)

PROJECT_TERMS: 3-Dimensional;arms race;Biological;Biophysics;Bystander Effect;Cancer Biology;cancer cell;Cancer cell line;Cancer Patient;cell killing;Cell Therapy;Cells;Chemicals;Clinical;Collaborations;combat;Combined Modality Therapy;Compensation;cost;Coupled;Cues;Data;design;Diffusion;Dimerization;Directed Molecular Evolution;drug development;drug discovery;Drug resistance;dual switch selection gene drive;effective therapy;efficacy evaluation;Endothelial Cells;Engineering;engineering design;Environment;Epidermal Growth Factor Receptor;Evolution;Exhibits;experimental study;Extracellular Matrix;Failure;Fibroblasts;fighting;fitness;gene drive system;Gene Library;Genes;Goals;Grant;Heterogeneity;Human;Immune;improved;In Situ;inhibitor;insight;Investigation;kinase inhibitor;Lead;Learning;Left;Lung;Malignant neoplasm of lung;Malignant Neoplasms;Mammalian Cell;Mathematics;Measurement;Measures;mimetics;Modeling;Mole the mammal;Molecular;mutant;Mutation;neoplastic cell;Non-Small-Cell Lung Carcinoma;novel therapeutics;Oncogenes;Oncologist;Organoids;Patients;Performance;Pharmaceutical Preparations;pharmacologic;prevent;Process;Prodrugs;programs;Protein Tyrosine Kinase;prototype;Reproducibility;Resistance;Resistance development;resistance mechanism;resistance mutation;Resolution;response;Reverse engineering;Risk;ROS1 gene;Safety;simulation;small molecule;standard of care;suicide gene;Suicide Gene Therapy;SWI1;Switch Genes;synthetic biology;systemic toxicity;Tacrolimus Binding Protein 1A;Techniques;Technology;Testing;Therapeutic;Toxicity Tests;Toxin;treatment response;tumor;tumor microenvironment;Tyrosine Kinase Inhibitor;Validation;Variant;Work

PROJECT_TITLE: Personalization and Failure Testing of Dual Switch Gene Drives in Lung Cancer


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Precision Medicine

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Project Narrative Using deconvolution approaches, we identified two tumor-intrinsic subtypes of PDAC (basal and classical) that are robust, replicable, prognostic and predictive of treatment response. We have also found two stroma subtypes associated with outcome and show tumor-stroma interactions in patients associated with outcome, recapitulated in tumor-CAF models. We will use a combination of cancer biology, computational approaches to determine tumor-stroma interactions and how they predict treatment response.

PI_NAMEs: RASHID, NAIM UR;TSAI, SUSAN ;YEH, JEN JEN  (contact)

PROGRAM_OFFICER_NAME: NOTHWEHR, STEVEN F

PROJECT_TERMS: Affect;Biological Assay;Biometry;Cancer Biology;Cell Communication;cell type;Cells;Characteristics;CLIA certified;Clinic;Clinical;clinical application;Clinical Trials;clinically relevant;Coculture Techniques;Computing Methodologies;Data;Data Set;Desmoplastic;early phase trial;Genes;Heterogeneity;immunoregulation;innovation;kinase inhibitor;Libraries;Manuscripts;Methods;Modeling;Molecular Profiling;molecular subtypes;multidisciplinary;Neoadjuvant Therapy;neoplastic cell;novel;Outcome;patient response;Patient-Focused Outcomes;Patients;Phosphotransferases;Positioning Attribute;predicting response;Prediction of Response to Therapy;Primary Neoplasm;prognostic;Proteome;response;Sampling;Selection for Treatments;Signal Transduction;single-cell RNA sequencing;standard of care;Systemic Therapy;Testing;Therapeutic;transcriptome;transcriptome sequencing;treatment effect;treatment response;tumor;tumor heterogeneity;tumor microenvironment;tumor progression;Tumor Subtype;Validation

PROJECT_TITLE: Integrating tumor and stroma to understand and predict treatment response


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Precision Medicine

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE The University of Michigan Center for Translational Cancer Proteogenomics (UM-CTCP) will perform advanced proteogenomics analyses a part of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiative. Working in collaboration with other members of the CPTAC, UM-CTCP will apply its advanced computational infrastructure for comprehensive and global characterization of genomics, transcriptomics, and proteomics data, collected from several cohorts of human tumors using NCI-provided biospecimens. UM- CTCP will conduct integrative analyses of data across these different data types with a goal to identify potentially cancer-related molecular alterations and to elucidate how distinct changes at the protein level are related to abnormalities in cancer genomes. A second priority of UM-CTCP is to assist with the selection of cancer-specific protein candidates for subsequent functional studies and validation using targeted assays.

PI_NAMEs: DHANASEKARAN, SARAVANA MOHAN ;NESVIZHSKII, ALEXEY I (contact)

PROGRAM_OFFICER_NAME: HILTKE, TARA

PROJECT_TERMS: Acceleration;Address;Adoption;Algorithms;Area;Benchmarking;bioinformatics tool;Biological;Biological Assay;Biological Markers;biomarker discovery;biomarker signature;Cancer Biology;cancer genetics;cancer genome;cancer genomics;cancer subtypes;cancer type;candidate selection;Cell Communication;Cells;Cellularity;Clinical;clinical implementation;clinically actionable;clinically relevant;Clonal Expansion;Code;cohort;Collaborations;Communities;computer infrastructure;computerized tools;computing resources;Copy Number Polymorphism;Data;Data Analyses;data modeling;Data Reporting;data visualization;Development;Disease;Early Detection Research Network;Ensure;Epigenetic Process;Event;experience;Foundations;Future;Gene Fusion;Generations;Genes;Genetic;genetic signature;Genome;genomic aberrations;Genomics;Goals;Histologic;Human;improved;Individual;individual patient;innovation;insight;inter-institutional;Investigation;Knowledge;Malignant Neoplasms;Measures;member;Methods;Michigan;Mission;Modeling;Molecular;molecular subtypes;multidisciplinary;multiple omics;Mutation;new technology;novel;novel strategies;Oncogenic;Oncology;oncology program;Pathologist;Pathology;Pathway Analysis;Patients;Peptides;Phenotype;Ploidies;Positioning Attribute;Post-Translational Protein Processing;precision oncology;Prognostic Marker;protein biomarkers;Proteins;proteogenomics;Proteome;Proteomics;Quality Control;Recording of previous events;Renaissance;Research;Research Personnel;Resources;SAGA;search engine;specific biomarkers;Speed;success;Systems Biology;technology development;therapeutic target;Time;Tissues;tool;transcriptome;transcriptomics;translational impact;Translations;tumor;Tumor Biology;tumor microenvironment;United States National Institutes of Health;Universities;Untranslated RNA;Validation;whole genome;Work;working group


ORG_CITY: ALBUQUERQUE

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: NARRATIVE There is a critical underrepresentation of cancers from American Indian patients in national cancer genome databases. Additionally, American Indians have the poorest cancer survival rates of all ethnicities in the United States. The goal of this proposal is to engage with American Indian communities and individuals in order to increase their understanding and participation in precision medicine, molecular characterization of tumors and cancer research with the long-term goal of reducing their cancer burden.

PI_NAMEs: TRENT, JEFFREY M.;WILLMAN, CHERYL LYNN (contact)

PROGRAM_OFFICER_NAME: MECHANIC, LEAH E

PROJECT_TERMS: Address;Agreement;Alaska Native;Alcohols;American Indian community;American Indian Tribe;American Indians;anti-cancer research;Behavior;Belief;biliary tract;Biological;Biological Markers;Breast;Cancer Burden;Cancer Etiology;cancer genome;cancer health disparity;Cancer Patient;cancer survival;Cancer Survivor;cancer type;Characteristics;Colorectal;Communication;Communities;community engagement;Data Commons;data sharing;Development;Diagnosis;Diet;differences in access;Disease;Disparity;DNA;Environmental Exposure;Ethnic Origin;Ethnic Population;Frequencies;Gallbladder;Genes;Genetic;Genome;genome database;genome sequencing;genome-wide;Genomics;Germ-Line Mutation;Goals;health care availability;Hepatitis;hepatobiliary cancer;Hormones;Human Papillomavirus;improved;Incidence;Indigenous;Individual;individualized prevention;Intervention;intravenous drug use;Kidney;Knowledge;Language;Liver;Malignant neoplasm of gastrointestinal tract;Malignant neoplasm of ovary;Malignant neoplasm of prostate;Malignant Neoplasms;Medical;Metabolism;Molecular;mortality;Mutation;Native Hawaiian or Other Pacific Islander;novel;novel diagnostics;Obesity;Outcome;Pancreas;Participant;patient engagement;Patients;personalized intervention;Policies;precision medicine;preventive intervention;Public Health;Publications;racial population;Religious Belief;Research;research study;Risk Behaviors;screening;Screening for cancer;Somatic Mutation;Stomach;Survival Rate;The Cancer Genome Atlas;Therapeutic Intervention;therapeutically effective;Tobacco;Translating;Translations;tribal community;Tribal Council;tribal Nation;Tribes;Trust;tumor;United States;United States National Institutes of Health;Urogenital Cancer;Vaccination;virtual;Virus;Visual

PROJECT_TITLE: Engagement of American Indians of Southwestern Tribal Nations in Cancer Genome Sequencing