NIH_SPENDING_CATS: Biotechnology;Genetics;Lung;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PI_NAMEs: HAWKINS, FINN  (contact)

PROJECT_TERMS: Address;Age;Airway Disease;airway epithelium;Alleles;Autologous;autosome;Basal Cell;Benchmarking;Biological;Biology;Caring;Cell Line;Cell Physiology;Cell Therapy;Cells;cellular engineering;Chronic lung disease;Cilia;cilium biogenesis;Clinical;clinical heterogeneity;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Communities;Cystic Fibrosis;Data;Defect;Development;Diagnosis;Disease;Dynein ATPase;early onset;effective therapy;Electron Microscopy;Engraftment;Ethnic Origin;experimental study;Frequencies;Functional disorder;gene correction;Genes;Genetic;Genetic Heterogeneity;Genetic Transcription;genetic variant;Genetic Variation;Genotype;Geography;Handedness;Heterogeneity;Human;Human Biology;human induced pluripotent stem cells;Immunoprecipitation;Impairment;improved;In Vitro;in vivo;in vivo evaluation;Incidence;Individual;induced pluripotent stem cell;Knock-out;Lead;Lung Diseases;Maps;Mass Spectrum Analysis;Methods;Modeling;Molecular;Morphology;Motility;Mucociliary Clearance;Mus;Mutation;novel;novel strategies;Pathogenicity;Patients;Penetrance;Phenotype;Pluripotent Stem Cells;Population;Precision therapeutics;Primary Ciliary Dyskinesias;Proteins;Proteomics;reconstitution;Reporting;Research;Role;self-renewal;Severity of illness;single-cell RNA sequencing;Source;Testing;Therapeutic;therapeutic development;therapeutic evaluation;Trachea;Transplantation;ubiquitin-protein ligase;Variant;variant of unknown significance;virulence gene

PROJECT_TITLE: Mapping genotype to phenotype in PCD using iPSCs


ADMINISTERING_IC: HL

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Genetics;Lung;Pulmonary Fibrosis;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Tobacco;Tobacco Smoke and Health

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

ORG_STATE: MA

PI_NAMEs: ALYSANDRATOS, KONSTANTINOS  (contact)

PROGRAM_OFFICER_NAME: LIN, SARA

PROJECT_TERMS: Adenosine Monophosphate;Adult;Agonist;Air;Alveolar;alveolar epithelium;Automobile Driving;Autophagocytosis;Biological Models;Biology;Cells;Cessation of life;Childhood;Coculture Techniques;CRISPR interference;Data;Development;Diagnosis;Disease;disease model;disease-causing mutation;Distal;druggable target;effective therapy;efficacy testing;Epithelium;Experimental Models;exposure to cigarette smoke;fibrogenesis;Fibrosis;Functional disorder;Gases;gene environment interaction;Genes;Genetic;genome wide association study;Glycolysis;Goals;Homeostasis;Human;human disease;human model;Idiopathic Interstitial Pneumonia;idiopathic pulmonary fibrosis;Impairment;In Vitro;in vivo;in vivo evaluation;induced pluripotent stem cell;Inflammatory;Interstitial Lung Diseases;knock-down;Liquid substance;Lung;Lung Diseases;Mediating;Mesenchymal;Mesenchyme;Metabolic;Methods;Mitochondria;mitochondrial dysfunction;Modeling;mouse model;mutant;novel;overexpression;Oxidative Phosphorylation;Pathogenesis;Pathway interactions;Patients;Phenotype;Pluripotent Stem Cells;Predisposition;progenitor;Protein Kinase;proteostasis;Publishing;Pulmonary Fibrosis;restoration;Role;self-renewal;single-cell RNA sequencing;Small Interfering RNA;stem cell model;Structure of parenchyma of lung;System;Testing;Therapeutic;Thyroid Hormones;Time;Variant;vector

PROJECT_TITLE: Patient-specific iPSCs to model and treat the inception of pulmonary fibrosis

STUDY_SECTION: HLBP

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: OVERALL NARRATIVE Despite the many recent advances in precision oncology, significant challenges remain in extending the benefits of this remarkable class of drugs to all cancer patients, particularly those with rare mutations in common cancer genes, those with rare cancers, and those from ethnic backgrounds that are not sufficiently represented in current precision oncology datasets. The investigators in our multi-disciplinary team will apply their complementary expertise to investigate these questions by leveraging the extensive observational data that can be accessed through a large, international clinico-genomic cancer registry called AACR Project GENIE.

PI_NAMEs: SAWYERS, CHARLES L. (contact)

PROGRAM_OFFICER_NAME: FILIPSKI, KELLY

PROJECT_TERMS: Address;American Association of Cancer Research;Bioinformatics;Biometry;Calibration;Cancer Center;cancer classification;cancer genomics;Cancer Patient;cancer risk;cancer subtypes;cancer therapy;checkpoint therapy;Clinical;Clinical Data;clinical decision-making;Clinical Trials;Clinical Trials Design;cohort;Collaborations;Communication;cost effective;Data;Data Analyses;Data Collection;data hub;data infrastructure;Data Set;data sharing;Diagnostic tests;digital pathology;Disease;DNA Sequence Alteration;driver mutation;Electronic Health Record;Ensure;Equity;Ethnic Origin;European;Event;Frequencies;Genetic;GENIE;genomic data;genomic profiles;Genomics;Germ Lines;Goals;Heterogeneity;Immune checkpoint inhibitor;Immunotherapy;improved outcome;Individual;Inequity;Infrastructure;innovation;Institution;International;Investigational Therapies;Knowledge;knowledge base;machine learning model;Malignant Neoplasms;Medicine;member;Memorial Sloan-Kettering Cancer Center;Methodology;molecular marker;molecular pathology;Molecular Profiling;multidisciplinary;Mutation;neoplasm registry;Occupational activity of managing finances;Office of Administrative Management;Oncogenes;Oncology;open source;optimal treatments;Outcome;Outcome Assessment;outcome prediction;pathology imaging;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Pharmacotherapy;Play;Population;Population Genetics;Population Sciences;precision medicine;precision oncology;Principal Investigator;Prognosis;prognostic;Program Research Project Grants;programs;Progression-Free Survivals;Publications;Race;rare cancer;Rare Diseases;rare variant;Registries;Reporting;Research Personnel;response;Role;Site;Somatic Mutation;Statistical Data Interpretation;targeted treatment;Time;Training;tumor;Work

PROJECT_TITLE: Leveraging Observational (Real World) Data to Advance Precision Oncology

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RPRB-6 (O1)]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Data Science;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine

PHR: PROJECT 1 NARRATIVE Research in precision cancer medicine requires large databases of molecular tumor characteristics linked to clinical information on responses to treatment. Efforts such as the AACR Project GENIE have gathered data on tumor characteristics for tens of thousands of patients, but the usefulness of this information has been limited by the difficulty of extracting and analyzing information on cancer outcomes from electronic health records, typically recorded as unstructured text. We will (1) evaluate a framework for medical record review to derive cancer endpoints by comparing framework-based annotations to traditional clinical trial endpoints; (2) develop cross-institutional artificial intelligence and natural language processing models to extract endpoints from physician reports automatically; and (3) evaluate a method for analyzing the resulting endpoints in the context of real-world data biases that may correlate with clinical risk.

PI_NAMEs: SCHRAG, DEBORAH  (contact)

PROJECT_TERMS: Acceleration;advanced analytics;American Association of Cancer Research;analytical method;anti-cancer research;Artificial Intelligence;artificial intelligence model;Biological Markers;biomarker identification;cancer type;Characteristics;Clinical;clinical care;clinical risk;Clinical Trials;cohort;Collaborations;Data;data modeling;Data Set;data standards;Databases;Disease;Disease Progression;Electronic Health Record;Event;federated learning;follow-up;GENIE;genomic data;Genomics;Goals;Healthcare Systems;Image;improved;Individual;individual patient;insight;Institution;interest;Knowledge;Link;Machine Learning;Malignant Neoplasms;Manuals;Measures;Medical Oncologist;Medical Records;Methodology;Methods;Modeling;Molecular;Natural Language Processing;novel;Oncology;Outcome;Pathology;Patients;Pattern;Performance;Physicians;Population;Population Heterogeneity;precision oncology;Progression-Free Survivals;Radiology Specialty;rare cancer;Reporting;Reproducibility;Research;Research Personnel;Resources;response;routine care;Selection for Treatments;Signs and Symptoms;simulation;Site;Solid Neoplasm;Source;Standardization;Structure;Testing;Text;Time;Training;treatment response;tumor;Vendor

PROJECT_TITLE: Project 1: Overcoming methodologic barriers to analysis of observational clinico-genomic data in oncology


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Lung;Lung Cancer;Precision Medicine;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

PHR: PROJECT 2 NARRATIVE Despite significant advances in cancer biology and clinical oncology, race- and ethnicity-based disparities in cancer outcomes remain a long-standing challenge. We propose to investigate how race, ethnicity, and genetic ancestry contribute to cancer outcomes in the largest publicly available registry of diverse cancer patients.

PI_NAMEs: ZHANG, JIAN  (contact)

PROJECT_TERMS: Accounting;African American;African American population;American Association of Cancer Research;Asian;Asian ancestry;Asian population;Automobile Driving;Awareness;Benchmarking;Biological Markers;Biology;Biomedical Research;Calibration;Cancer Biology;Cancer Etiology;cancer health disparity;Cancer Patient;cancer risk;cancer type;Categories;Clinic;Clinical;Clinical Data;Clinical Oncology;clinical sequencing;Collaborations;Collection;Colorectal Cancer;Complex;Computing Methodologies;Data;Disparity population;Epidermal Growth Factor Receptor;ethnic disparity;Ethnic Origin;Ethnic Population;Etiology;European ancestry;exome;exome sequencing;Frequencies;Future;Genes;Genetic;Genetic Determinism;Genetic study;GENIE;genome sequencing;genome-wide;Genomics;Germ Lines;Germ-Line Mutation;health disparity;High-Throughput Nucleotide Sequencing;Human;Human Characteristics;Immunotherapy;improved;Individual;Institution;Knowledge;loss of function mutation;Malignant neoplasm of prostate;Malignant Neoplasms;Methodology;Methods;Modeling;Molecular;Molecular Profiling;molecular scale;multi-ethnic;Mutation;Nature;non-genetic;Non-Small-Cell Lung Carcinoma;novel;Oncogenes;Outcome;Pathogenicity;Play;Population;Population Heterogeneity;precision oncology;Prognosis;prognostic;Protocols documentation;Public Domains;Race;racial difference;racial disparity;Recording of previous events;Recurrence;Registries;Research Personnel;Resolution;Risk;Role;Sampling;social;social health determinants;targeted sequencing;The Cancer Genome Atlas;transcriptome sequencing;triple-negative invasive breast carcinoma;tumor;Variant;White Women

PROJECT_TITLE: Project 2: Integrating race, ethnicity, and genomic ancestry across GENIE to understand genetic and environmental contributions to pan-cancer risk, prognosis, and outcomes


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Comparative Effectiveness Research;Genetics;Human Genome;Immunotherapy;Precision Medicine

PHR: PROJECT 3 NARRATIVE This project will leverage the large AACR Project GENIE clinical-genomic database to determine clinical outcomes of subsets of patients receiving immunotherapy and patients with rare mutations, and to evaluate the contribution of co-mutations, neoantigens, and expression signatures to response outliers. Findings will be incorporated into a clinical decision-making tool in OncoKB, a recognized resource for cancer precision medicine practitioners.

PI_NAMEs: SCHULTZ, NIKOLAUS  (contact)

PROJECT_TERMS: Address;American Association of Cancer Research;Biological Products;BRAF gene;Calibration;cancer type;Characteristics;checkpoint therapy;Clinical;clinical decision-making;Clinical Trials;clinically actionable;Collaborations;Data;data integration;Data Set;Databases;DNA Sequence Alteration;driver mutation;Drug Labeling;efficacy outcomes;ERBB2 gene;evidence base;Gene Expression Profile;Genes;GENIE;genomic biomarker;genomic data;genomic signature;Genomics;Goals;Immune checkpoint inhibitor;Immunologic Markers;Immunotherapy;improved;improved outcome;Individual;inhibitor;knowledge base;Label;Level of Evidence;Link;Malignant Neoplasms;Methodology;Mitogen-Activated Protein Kinases;molecular marker;Mutation;neoantigens;neoplasm resource;Oncogenic;Outcome;outcome prediction;Pathologic;Pathway interactions;patient subsets;Patient-Focused Outcomes;Patients;Pattern;Pharmacy facility;precision medicine;precision oncology;predictive tools;Progression-Free Survivals;prospective;rare variant;Records;Registries;repository;response;Sampling;Single Nucleotide Polymorphism;Specificity;survival outcome;targeted agent;targeted treatment;tool;transcriptomics;treatment and outcome;Treatment outcome;treatment response;tumor;Variant

PROJECT_TITLE: Project 3: Predictors of sensitivity to immunotherapy and targeted treatments based on real world evidence


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

PHR: NARRATIVE This P01 program is multi-institutional collaboration that will purse research to enhance the implementation and practice of precision oncology. The Administrative Core manages P01 Program activities including: budget and resource allocation, data sharing pipelines, research administration, and federal agency compliance.

PROJECT_TERMS: American Association of Cancer Research;Bioinformatics;Budgets;cBioPortal;Clinical Data;Collaborations;Collection;Communication;Communities;Computer Systems;conflict resolution;Data;Data Collection;data harmonization;data hub;data integrity;data management;data sharing;Decision Making;Doctor of Philosophy;electronic data;Ensure;Expenditure;Fostering;General Population;GENIE;genomic data;Grant;Health Insurance Portability and Accountability Act;Human Resources;Individual;Infrastructure;Institution;instrument;Lead;Leadership;Life Cycle Stages;Medical;meetings;molecular pathology;Monitor;National Cancer Institute;Occupational activity of managing finances;Office of Administrative Management;Patients;Performance;Policies;precision oncology;Principal Investigator;Process;Production;Program Research Project Grants;programs;Progress Reports;Publications;quality assurance;Regulation;Reporting;Research;Research Personnel;Resource Allocation;Risk;Risk Management;Services;Site;Statistical Data Interpretation;Training;United States National Institutes of Health;Update;Validation;Visualization

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Cancer Genomics;Data Science;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine

PHR: CORE A NARRATIVE The overarching goal of this core is to ascertain “real world” clinical outcomes with rigor and reproducibility and to ensure that the inferences made from the resulting observational databases are reliable and reported with transparency. We accomplish this by coordinating curation and interpretation efforts to apply PRISSMM, a tumor-site agnostic data model to specification of oncologic outcomes from EHR data. Broad availability of high- quality tumor genomic data linked to treatment exposures and survival outcomes will propel further advances in precision oncology and translational research.

PI_NAMEs: PANAGEAS, KATHERINE S (contact)

PROJECT_TERMS: Academy;Address;Agreement;Algorithms;American Association of Cancer Research;Articulation;Biological Assay;Biometry;Cancer Center;cancer type;Clinical;Clinical Data;Clinical Trials;clinically actionable;Code;Collaborations;Complex;Controlled Clinical Trials;Data;Data Analyses;Data Collection;data curation;data harmonization;data modeling;data quality;Data Set;Data Sources;data standards;Databases;Dedications;design;Diagnosis;Disease Progression;Electronic Health Record;Elements;Ensure;Generations;GENIE;genomic data;genomic profiling;Genomics;Glean;Goals;Health system;Histology;Image;imaging study;Individual;Institution;Kidney;Knowledge;Leadership;Link;Logic;machine learning algorithm;Malignant Neoplasms;Manuscripts;Measurement;Measures;Medical Oncologist;Melanoma;Methodology;Modeling;Molecular;Molecular Profiling;next generation sequencing;Oncology;Outcome;Ovarian;Pathology;Pathology Report;patient population;Patients;phenomics;precision medicine;precision oncology;predictive marker;Private Sector;Process;Program Research Project Grants;Progression-Free Survivals;Public Sector;quality assurance;radiologist;Radiology Specialty;Recommendation;Reporting;Reproducibility;Research Design;Resource Sharing;response;Roentgen Rays;Role;Signs and Symptoms;Site;Source;Specific qualifier value;Standardization;Statistical Data Interpretation;statistics;Structure;survival outcome;Therapeutic;Time;Training;Translational Research;treatment response;tumor;Tumor Markers;ultrasound;unstructured clinical data;Update;Work

PROJECT_TITLE: Core A: Curation and Statistical Analysis Core


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

PHR: CORE B NARRATIVE The Molecular Pathology and Bioinformatics Core will perform deep molecular characterization of tumors collected from patients across all participating cancer centers to identify DNA- and RNA-based features that correlate with clinical outcomes. In line with the goals of the Research Projects, we will select and prioritize tumors representing underrepresented populations, subclasses of patients who have received immunotherapy, and ERBB2 and BRAF fusion cancer types, and that benefit from coordinated efforts across many institutions to adequately study.

PI_NAMEs: BERGER, MICHAEL F. (contact)

PROJECT_TERMS: American Association of Cancer Research;Bioinformatics;bioinformatics pipeline;BRAF gene;Cancer Center;cancer type;checkpoint therapy;Clinical;Clonality;Collaborations;Data;data sharing;Diagnosis;digital pathology;DNA;Doctor of Philosophy;driver mutation;ERBB2 gene;exome sequencing;Gene Expression Profile;GENIE;genomic platform;Genomics;Goals;Image;Immunotherapy;Individual;Institution;Knowledge;Loss of Heterozygosity;Malignant Neoplasms;member;Methods;Molecular;Molecular Analysis;molecular pathology;molecular subtypes;multiple omics;Mutation;Normal tissue morphology;novel;Nucleic Acids;Outcome;Pathology;pathology imaging;Pathway interactions;Patient Selection;patient subsets;Patients;Population;precision oncology;Protocols documentation;rare cancer;Recurrence;repository;Research;Research Project Grants;Resolution;response;Retrieval;RNA;Running;Sampling;Scanning;Site;Slide;Specimen;Standardization;Statistical Methods;Supervision;Testing;tissue preparation;Tissue Sample;Tissues;transcriptome sequencing;transcriptomics;tumor;Underrepresented Populations;Variant;Work

PROJECT_TITLE: Core B: Molecular Pathology and Bioinformatics Core


ADMINISTERING_IC: TR

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

NIH_SPENDING_CATS: Brain Disorders;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: Project Narrative Leukodystrophies are a collection of rare genetic disorders that are predominantly fatal, progressive disorders of childhood with few targeted therapeutic options. Exciting recent advances, including gene therapy development for adrenoleukodystrophy and metachromatic leukodystrophy, underscore the critical need for continued innovation and a pipeline of future translational researchers interested in rare diseases. Leveraging resources within the Rare Diseases Clinical Research Network Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN) and educational expertise of the Institute for Translational Medicine and Therapeutics Education (ITMAT Ed) program, we propose an education program, the Predoctoral Preparatory Program (P3), targeting junior research coordinators within the GLIA-CTN which will (1) provide a curriculum related to responsible conduct of research and (2) prepare the next generation of physician scientists in translational research through professional development workshops and mentorship.

PI_NAMEs: ADANG, LAURA ANN (contact)

PROGRAM_OFFICER_NAME: URV, TIINA K

PROJECT_TERMS: Address;Adrenoleukodystrophy;Affect;Age;Area;career;Career Choice;career development;Career Exploration;Cerebrum;Child;Childhood;Clinical Research;Clinical Trials Network;Collaborations;Collection;Communication;Communities;community building;Critical Thinking;design;Development;Development Plans;Disease;Education;Educational Curriculum;Educational process of instructing;Educational workshop;Enrollment;Environment;expectation;experience;Exposure to;Foundations;Funding;Future;gene therapy;Goals;hands on research;Hour;Individual;Infrastructure;innovation;Institution;interest;Internet;Lead;leukodystrophy;medical schools;Medicine;meetings;Mentors;Mentorship;Metachromatic Leukodystrophy;Myelin;Neurologic;next generation;novel;Pediatric Hospitals;Pennsylvania;Persons;Philadelphia;Physicians;Population;pre-doctoral;Process;programs;Rare Diseases;rare genetic disorder;recruit;Research;research and development;Research Personnel;Resources;responsible research conduct;Science;Scientist;Self Perception;Site;skill acquisition;skills;symposium;Targeted Research;targeted treatment;Therapeutic;therapeutic development;therapy development;tool;translational medicine;Translational Research;translational scientist;translational therapeutics;Underrepresented Populations;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: Predoctoral Preparatory Program (P3) in Translational Research

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Developmental Biology Study Section[CHHD-C]


ADMINISTERING_IC: DK

ED_INST_TYPE: COLLEGES OF PODIATRIC MEDICINE

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: NORTH CHICAGO

ORG_DEPT: OTHER CLINICAL SCIENCES

ORG_NAME: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI

ORG_STATE: IL

PHR: PROJECT NARRATIVE The Summer Research Fellowship Program for Podiatric Medical Students seeks to increase the number of podiatric medical students entering careers in biomedical sciences. This is especially important in the field of diabetes, as foot pathology is one of the most common complications affecting the 29 million people in the United States living with the disease. Students who have participated in the program have produced numerous peer- reviewed publications, research abstracts, awards and grant funding in contribution to diabetes-related research.

PI_NAMEs: ROSENBLATT, NOAH  (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Address;American;Basic Science;Biomedical Research;career;Clinical Research;college;Communities;Data Analyses;Data Collection;Degree program;Diabetes Mellitus;Discipline;Doctor of Philosophy;Environment;experience;Exposure to;Faculty;Fellowship Program;foot;Fostering;Goals;Grant;Individual;Institution;Institutionalization;interest;Medical;Medical Research;Medical Students;Mentors;Mentorship;Mind;Oral;Pathology;Patients;Podiatry;Population;pre-doctoral;programs;recruit;Research;Research Personnel;Research Support;Schools;Science;Scientist;skills;Students;success;summer research;support network;Talents;Training;Training and Education;Training Programs;Translational Research;Work;Writing

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


ADMINISTERING_IC: AI

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Infectious Diseases;Social Determinants of Health

ORG_CITY: HOUSTON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: RICE UNIVERSITY

ORG_STATE: TX

PHR: Project Narrative To address the glaring lack of diversity at the highest levels of infectious disease research—and with the biomedical research community in general—PIs at Rice University and Houston Community College (HCC) will Augment Community College Education to Leverage Experiential Research and Advance Training Equity (ACCELERATE) by providing enhanced opportunities to HCC students from historically underrepresented groups. Specifically, the ACCELERATE Program will consist of professional development seminars; literature review training; laboratory modules for technical skill development; mentored summer research internships in infectious disease labs at Rice University and the Texas Medical Center (TMC); and mentorship from the Program PIs, HCC faculty, TMC investigators, and postdocs and graduate students. Given these opportunities and the support of their mentor and peer networks, students will be well-positioned to transfer to four-year universities, pursue research at those institutions, gain entrance to top graduate schools, and ultimately attain leadership positions to increase the diversity of the national biomedical workforce.

PI_NAMEs: MAHON, BRIAN ;MCHUGH, KEVIN JAMES (contact);NICHOL, CAROLYN AITKEN;STEAR, JEFF

PROGRAM_OFFICER_NAME: MOTEN, CARMEN

PROJECT_TERMS: Achievement;Address;Admission activity;Affect;Associate Degree;Attention;Biology;Biomedical Research;Black race;career;career development;Career Mobility;career networking;Charge;cohort;Collaborations;college;Color;Communicable Diseases;Communities;community college;Consultations;Decision Making;Development;doctoral student;Dropout;Education;Educational Curriculum;Educational Status;Elements;Engineering;Enrollment;Ensure;Equity;ethnic minority population;Exclusion;experience;Faculty;faculty mentor;forging;Fostering;Funding;Goals;graduate school;graduate student;Grant;health care disparity;Hispanic;improved;Individual;Infectious Diseases Research;insight;Institution;interest;Internships;Journals;Knowledge;Laboratories;laboratory curriculum;laboratory module;Leadership;Link;Lived experience;Low income;Measures;Medical center;Mentors;Mentorship;minority scientist;Minority-Serving Institution;Mission;Motivation;National Institute of Allergy and Infectious Disease;Occupations;Participant;peer;peer networks;Performance;Persons;Population;Positioning Attribute;Postdoctoral Fellow;Program Description;programs;promote resilience;Public Health;Qualifying;Recommendation;recruit;Research;Research Personnel;Research Training;Resource Development;Resources;Review Literature;Rice;Role;scaffold;Science;Science Policy;Series;skill acquisition;skills;STEM student;student participation;Student Selections;Students;success;summer program;summer research;supplemental instruction;symposium;System;Teacher Professional Development;Technical Expertise;Texas;Touch sensation;Training;Training and Education;transfer student;undergraduate student;Underrepresented Minority;underrepresented minority student;Underrepresented Populations;United States;United States National Institutes of Health;Universities;university student;Writing

PROJECT_TITLE: Rice-HCC ACCELERATE: Augmenting Community College Education to Leverage Experiential Research and Advance Training Equity

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 TC-D (S1)]


ADMINISTERING_IC: EB

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

ORG_CITY: MINNEAPOLIS

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE (OVERALL) This biotechnology research center project establishes a national resource that will provide cutting edge technologies to enable the use of magnetic resonance imaging (MRI) devices running at ultrahigh magnetic fields of 10.5T and 16.4T as sensitive tools for basic and clinical research. Combining these unique MRI capabilities with non-MR methods of advanced electrophysiology and multiphoton optical imaging system, a first of its kind, will be used to provide novel insights into brain function and connectivity from single neurons to the whole brain. Clinical research will benefit from the development of advanced methods that report on physiological and molecular processes where UHF will provide increased sensitivity assessing disease progression and evaluating treatment response. Specific engineering, physics and image reconstruction strategies will be implemented to realize the full potential of UHF systems.

PI_NAMEs: METZGER, GREGORY JOHN (contact);UGURBIL, KAMIL

PROGRAM_OFFICER_NAME: LIU, GUOYING

PROJECT_TERMS: 3-Dimensional;Acceleration;Address;Advanced Development;Algorithms;Amplifiers;Animal Model;Area;Basic Science;Biomedical Research;Biotechnology;Brain;Callithrix;Cell Nucleus;Clinical Research;Cognitive Science;Data;deep learning;denoising;design;Development;Disease;Disease Progression;Electrodes;Electronics;Electrophysiology (science);Engineering;experimental study;Future;Goals;Health;Health care facility;hemodynamics;high resolution imaging;Housing;Human;human imaging;Image;image reconstruction;Imaging Device;imaging study;imaging system;Imaging technology;improved;insight;integrated circuit;Joint repair;lens;Link;magnetic field;Magnetic Resonance Imaging;Malignant Neoplasms;Maps;Measurement;Methods;miniaturize;Modality;Modeling;Molecular;Molecular Probes;multi-photon;Multimodal Imaging;multimodality;multiphoton imaging;Musculoskeletal Diseases;Names;Nervous System Disorder;Neurons;Neurosciences;new technology;next generation;Noise;nonhuman primate;novel;Nuclear;optical imaging;Organism;Parameter Estimation;Phase;Physics;Physiologic pulse;Physiological;Process;Property;Protons;radio frequency;reconstruction;Relaxation;Reporting;Research;research and development;Resolution;Resources;Rotation;Running;Safety;safety assessment;senescence;Services;Signal Transduction;spatiotemporal;Spectrum Analysis;success;Synapses;System;Technology;Tissues;tool;Training;transmission process;treatment response;vascular contributions;Visual Cortex;Work

PROJECT_TITLE: Technology to Realize the Full Potential of UHF MRI

STUDY_SECTION_NAME: Special Emphasis Panel[ZEB1 OSR-D (O1)]


PI_NAMEs: METZGER, GREGORY JOHN (contact)

PROJECT_TERMS: Address;Advisory Committees;Biomedical Engineering;biomedical imaging;Biomedical Research;Biotechnology;Collaborations;Development;Ensure;experience;Faculty;Goals;Guidelines;Incidental Findings;Infrastructure;innovation;Institution;Institutional Review Boards;instrumentation;Interdisciplinary Study;Leadership;magnetic field;Magnetic Resonance;Magnetic Resonance Imaging;meetings;Methodology;Minnesota;National Institute of Biomedical Imaging and Bioengineering;operation;optical imaging;organizational structure;Personnel Management;Procedures;Process;programs;Progress Reports;Reporting;Research;Research Personnel;Resource Development;Resources;Role;Safety;Services;supportive environment;System;Technology;technology development;technology research and development;tool;Training;Universities;web based interface

PROJECT_TITLE: Administration Core


PI_NAMEs: ZIMMERMANN, JAN  (contact)

PROJECT_TERMS: Algorithms;Animal Model;Animals;Automobile Driving;Blood Vessels;Brain;Breeding;Callithrix;cell type;Cells;Complement;Complex;connectome;Contracts;Core-Binding Factor;Cortical Column;Coupling;Data;data acquisition;Detection;Development;Diffusion Magnetic Resonance Imaging;Electrodes;Electrophysiology (science);experimental study;Film;Functional Imaging;Functional Magnetic Resonance Imaging;Funding;Goals;Grant;Health care facility;hemodynamics;Housing;Human;Image;image reconstruction;improved;interest;Investigation;Investments;Lead;Macaca mulatta;magnetic field;Magnetic Resonance Imaging;Maps;Measurement;Mediating;Methodology;Methods;Minnesota;Modality;Modeling;mouse model;multi-photon;Multimodal Imaging;multimodality;multiphoton imaging;multiphoton microscopy;Nature;Neurons;neurovascular coupling;new technology;Noise;nonhuman primate;novel;novel strategies;optical fiber;optical imaging;Optics;optogenetics;Phase;Photons;Physiologic pulse;Physiological;Physiology;Positioning Attribute;Process;promoter;Research Personnel;Resolution;response;Signal Transduction;Site;Slice;spatiotemporal;Specificity;success;System;Techniques;Technology;temporal measurement;Thick;Thinness;Time;tool;two-photon;ultra high resolution;Universities;vascular contributions;Veins;Visual Cortex

PROJECT_TITLE: TRD1: Multimodal Imaging for Spanning Multiple Spatial Scales in the Brain; Expansion to New Technologies and Species


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Machine Learning and Artificial Intelligence

PROJECT_TERMS: Acceleration;Address;Advanced Development;anatomic imaging;Anatomy;angiogenesis;animal imaging;Area;arterial spin labeling;Biological Markers;Biomedical Research;Blood;Brain;Cell Nucleus;Clinical;clinical application;clinical translation;Collaborations;Computer software;contrast imaging;Data;data integration;denoising;Development;Disease;experience;experimental study;Functional Imaging;Goals;Health;Heating;human imaging;Image;imaging platform;imaging system;improved;in vivo;innovation;machine learning model;magnetic field;Magnetic Resonance Imaging;Maps;Measures;Metabolism;method development;Methods;Modality;Molecular;molecular dynamics;molecular imaging;molecular marker;neurovascular coupling;new technology;Noise;novel;novel strategies;Nuclear;Organism;Parameter Estimation;Performance;Perfusion;Phase;Physiological;Process;Property;Protocols documentation;Protons;reconstruction;Relaxation;Research;Resolution;RF coil;Rotation;Services;Signal Transduction;Spectrum Analysis;success;System;system architecture;Technology;temporal measurement;Tissues;transmission process;Work

PROJECT_TITLE: TRD2: Mapping of Molecular and Physiological Tissue Properties at UHF


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

PI_NAMEs: AKCAKAYA, MEHMET  (contact)

PROJECT_TERMS: absorption;Acceleration;Address;Algorithms;Anatomy;Calibration;Cell Nucleus;Classification;convolutional neural network;cost;Data;Data Set;data space;Databases;deep learning;denoising;design;Development;Ensure;Goals;Grant;high resolution imaging;Image;image reconstruction;Imaging technology;improved;Joint repair;Joints;Lead;lens;Link;Machine Learning;Magnetic Resonance Imaging;Maps;Methodology;Methods;Modality;Modeling;Motion;Multimodal Imaging;multimodal neuroimaging;multimodality;new technology;Noise;novel;novel strategies;optical imaging;Performance;Periodicity;Phase;Physics;Physiologic pulse;Protons;radio frequency;reconstruction;Recovery;resilience;Resolution;Scanning;self supervised learning;Series;Side;Signal Transduction;statistics;Structure;Techniques;Technology;technology development;Training;Translations;transmission process;voltage;voltage sensitive dye

PROJECT_TITLE: TRD3: Intelligent Physics-Driven Technologies for Inverse Problems in UHF Applications


PI_NAMEs: ADRIANY, GREGOR  (contact)

PROJECT_TITLE: TRD4: RF Coil Development for Capturing Ultimate Intrinsic SNR in UHF MRI


PROJECT_TERMS: Biochemical;Biomedical Engineering;biomedical imaging;Biomedical Research;Biotechnology;Clinical;Clinical Investigator;Communities;Complex;Computer software;computerized data processing;Computers and Advanced Instrumentation;connectome;Continuing Education;Data;Development;digital;Disease;Education;Educational workshop;Electrophysiology (science);Equipment;experience;experimental study;Faculty;Goals;graduate student;Health;Hospitals;Human;Image;image processing;image reconstruction;imaging modality;Individual;Industry;Institution;instrument;instrumentation;International;Investments;Journals;Laboratories;large scale data;lectures;magnetic field;Magnetic Resonance;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Measurement;member;Methodology;Methods;Minnesota;multidisciplinary;Multimodal Imaging;multiphoton imaging;novel;Organ;Participant;Peer Review;Physiologic pulse;Postdoctoral Fellow;posters;Process;Protocols documentation;Publications;reconstruction;recruit;Research;Research Personnel;Resources;Scientist;Series;skills;Source;Spectrum Analysis;Students;symposium;Teaching Materials;Techniques;Technology;technology research and development;Text;tool;Training;Training Activity;translational scientist;Universities;Visit;web app;web based software;web site

PROJECT_TITLE: Training and Dissemination


NIH_SPENDING_CATS: Hematology

ORG_CITY: IOWA CITY

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE The training program has as its primary objective to prepare MD, MD/PhD, and PhD postdoctoral fellows for productive careers in the hematology research workforce. There is a particular need to expand the number of scientists and physician-scientists trained in research in the field of hematology because of its direct relevance to some of the most common human medical conditions, including abnormalities of immune cells, vascular diseases, disorders of blood clotting, and sickle cell disease.

PI_NAMEs: CHAUHAN, ANIL KUMAR;LENTZ, STEVEN R (contact)

PROGRAM_OFFICER_NAME: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN

PROJECT_TERMS: Blood Cells;Cellular biology;Hematology;Molecular Biology;programs

PROJECT_TITLE: Program in Hematology:  Molecular & Cell Biology of Blood Cells

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM (OA)]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PROJECT NARRATIVE Identifying and cataloging the occurrence of structural variants (SVs)—including deletions, insertions, duplications, and inversions—in human chromosomes is essential for comprehensively understanding genetic disease risk and developing precision medicine approaches to mitigate disease. However, despite significant advances in long-read sequencing technology and genome assembly methods, many SVs can still not be assembled accurately, and improved methods and resources are required for genotyping, ascertaining functional relevance of SVs, and associations of SVs with specific phenotypic traits. We will capitalize on our combined expertise to develop the most comprehensive resource of human genome structural variation and significantly improve methods for SV detection, characterization and phenotype association to aid researchers and clinicians in understanding the role of SVs in genetic disease.

PI_NAMEs: EICHLER, EVAN ;KORBEL, JAN OLIVER;LEE, CHARLES  (contact);MARSCHALL, TOBIAS

PROGRAM_OFFICER_NAME: ARGUELLO, ALEXANDER

PROJECT_TERMS: Adoption;advanced analytics;analytical tool;arm;autism spectrum disorder;Awareness;Benchmarking;biobank;Biology;Cataloging;Catalogs;Centromere;Chromatin Structure;Chromosomes;Clinical;cohort;Collaborations;Communities;Complex;computational pipelines;Computer software;Computing Methodologies;cost;Data;data dissemination;data exchange;data integration;Data Set;Data Sources;data standards;Databases;Dedications;Disease;disorder risk;DNA Methylation;effectiveness evaluation;Elements;epigenomics;Event;Exclusion;Family;Future;Gene Expression;Generations;Genetic Diseases;Genetic Polymorphism;genetic variant;Genetic Variation;Genome;genome sequencing;Genomic Segment;Genomics;Genotype;Geographic Locations;Goals;Graph;Haplotypes;Health;Human;Human Chromosomes;Human Genetics;Human Genome;human pangenome;Human Resources;improved;Individual;International;Methods;Minisatellite Repeats;Molecular;molecular phenotype;National Human Genome Research Institute;novel;Nucleotides;Parents;Phase;Phenotype;Population;Population Heterogeneity;precision medicine;preservation;Qualifying;Quantitative Trait Loci;Research;Research Personnel;Resolution;Resources;RNA Splicing;Role;Sampling;Signal Transduction;Surveys;Technology;telomere;tool;Training;trait;Variant;variant detection;Visualization;Visualization software;whole genome;Work

PROJECT_TITLE: Identifying and Characterizing the Full Spectrum of Haplotype-resolved Structural Variation in Human Genomes

STUDY_SECTION_NAME: Special Emphasis Panel[ZHG1 HGR-M (O1)]


NIH_SPENDING_CATS: Clinical Research;Health Services

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Emergency medicine and hospital medicine are the foundation of hospital-based care for acute heart, lung, and blood disorders yet are underrepresented in scientific career development efforts. Drawing on institutional strengths in research training, scientific career development, and learning health systems, we propose the Vanderbilt Interdisciplinary Hospital-based Systems of Care Research Training Program (VISTA) for postdoctoral fellows. To improve hospital-based care in NHLBI priority areas, VISTA will provide rigorous mentored research training in discovery, evidence translation, data science, policy and epidemiology, and operations research, incorporating stakeholder engagement and health equity throughout the program.

PI_NAMEs: KRIPALANI, SUNIL ;STORROW, ALAN B;WARD, MICHAEL J. (contact)

PROGRAM_OFFICER_NAME: ROPER, REBECCA

PROJECT_TITLE: Vanderbilt Interdisciplinary Hospital-Based Systems of Care Research and Training ProgrAm (VISTA)


NIH_SPENDING_CATS: Asthma;Clinical Research;Data Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: MADISON

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Identifying modifiable prenatal and early life risk factors is crucial for developing strategies to prevent childhood asthma. While individual birth cohort studies have identified several asthma-related genetic, personal and environmental risk factors, these studies were mainly limited to homogeneous cohorts and modest sample sizes. We propose establishing a children's allergy and asthma data hub (The Children's Allergy and Asthma Data Repository, or “CADRE”) to ensure enduring access for the scientific community to allergy and asthma birth cohort data.

PI_NAMEs: GERN, JAMES E. (contact)

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: 17q12;Address;Affect;airway epithelium;Allergic Disease;analytical method;Asthma;Birth;Characteristics;Child;Child Health;Childhood;Childhood Asthma;Clinical;clinical phenotype;cohort;Cohort Studies;Collaborations;Communities;Consultations;Data;Data Analytics;data ecosystem;Data Element;data harmonization;data hub;data management;Data Pooling;data quality;data repository;Data Set;data sharing;DNA Methylation;early childhood;Electronic Health Record;Enrollment;Ensure;Environmental Risk Factor;Epithelial Cells;Ethics;ethnic disparity;Ethnic Origin;Extrinsic asthma;FAIR principles;Family;Foundations;Funding;Future;Genes;Genetic;Genetic Polymorphism;Geography;Goals;Health protection;Hypersensitivity;Incidence;Individual;Infant;Infrastructure;Intake;Investments;Life;Life Cycle Stages;Measurement;Metadata;multidimensional data;Natural History;Neighborhoods;Outcome;Participant;Phenotype;prenatal;preservation;prevent;Privacy;privacy protection;Procedures;Process;programs;Proteins;Publications;Quality Control;Questionnaires;Race;racial disparity;recruit;Reporting;repository;Research;Research Personnel;Resources;respiratory;Risk;Risk Factors;Rural;Sample Size;Sampling;Secure;Services;social;Socioeconomic Status;Source;Standardization;Structure;suburb;System;tool;United States National Institutes of Health;usability;Wheezing

PROJECT_TITLE: Children's Allergy and Asthma Data Repository (CADRE)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-T (55)]


NIH_SPENDING_CATS: Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: SAN JUAN

ORG_NAME: COMPREHENSIVE CANCER CENTER/ UNIV/PR

ORG_STATE: PR

PHR: Project Narrative Since 2019, the Cancer Prevention and Control (CAPAC) Research Training Program has organized mentored cancer research experiences in Puerto Rico for master-level and health professional students from diverse racial/ethnic backgrounds, with a focus on Hispanic populations. This unique program has resulted in successful scientific outcomes for its trainees, including cancer research experiences along the cancer control continuum, conference presentations, publications, and acceptance into doctoral programs. During the renewal period, CAPAC will increase the number of trainees, integrate new topics in the educational activities, and continue the development of the next generation of cancer researchers by mentoring and fostering participants and providing them the knowledge and skills to pursue a doctoral degree and/or academic and professional careers in cancer prevention and control research.

PI_NAMEs: ORTIZ, ANA PATRICIA (contact);SOTO-SALGADO, MARIEVELISSE

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: anti-cancer research;Area;Artificial Intelligence;Awareness;Cancer Burden;Cancer Control;Cancer Control Research;cancer health disparity;cancer prevention;cancer risk;career;career development;Clinical;cohort;Collaborations;college;Comprehensive Cancer Center;COVID-19 pandemic;Cultural Backgrounds;cultural competence;Cultural Sensitivity;Development;Disparity;Disparity population;Division of Cancer Control and Population Sciences;Doctor's Degree;Education;education research;Educational Activities;Educational workshop;Eligibility Determination;Enrollment;Ensure;Environment;ethnic minority;ethnic minority population;Ethnic Origin;Ethnic Population;Evaluation;experience;Exposure to;Faculty;Family;follow-up;Fostering;Funding;Gender;Geography;Goals;Graduate Degree;hands on research;Health;Health Disparities Research;health disparity;health disparity populations;Health Professional;Hispanic;Hispanic Populations;Institution;Intention;interest;Interview;Journals;Knowledge;Leadership;Letters;Malignant Neoplasms;Manuscripts;Master of Science;meetings;member;Mentors;Minority;Minority Groups;Minority Health Research;Modality;Modeling;next generation;Not Hispanic or Latino;Outcome;Participant;Patient Recruitments;peer;peer coaching;Peer Review;Performance;Politics;Population;Population Research;Process;Productivity;professional students;programs;Publications;Publishing;Puerto Rican;Puerto Rico;Race;racial diversity;racial minority population;racial population;Recommendation;recruit;Research;Research Personnel;satisfaction;skills;social culture;Societies;Students;Subgroup;success;summer program;Surveys;symposium;Techniques;Time;Training Programs;Underrepresented Populations;Underserved Population;United States;Universities;Work;Writing

STUDY_SECTION: NCI

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: STONY BROOK

ORG_DEPT: PHARMACOLOGY

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: Narrative The SBMS training program provides didactic training in translational science and supports clinical research opportunities for PhD candidates starting their second or third year of doctoral training. The goal of this program is to expose the students to biomedical research, promote an understanding of the challenges of medical research, bridge the gap between basic biology and medical practice and provide relevance and urgency to basic science research and establish collaborations between basic and clinical researchers.

PI_NAMEs: TSIRKA, STYLIANI-ANNA (STELLA) E (contact)

PROGRAM_OFFICER_NAME: NELSON, SHAKIRA M

PROJECT_TERMS: Science;Training Programs

PROJECT_TITLE: Scholars in BioMedical Sciences (SBMS) Training Program

STUDY_SECTION: TWD

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


NIH_SPENDING_CATS: Hematology;Infectious Diseases;Sepsis

ORG_CITY: PITTSBURGH

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE Trauma and sepsis are among the leading causes of death and morbidity worldwide. We propose to train surgeon-scientists uniquely prepared to identify and address the most pressing questions limiting progress in the management of trauma and sepsis patients.

PI_NAMEs: BILLIAR, TIMOTHY R (contact)

PROGRAM_OFFICER_NAME: PRICE, AMANDA ALISE

PROJECT_TERMS: Research;Sepsis;Training;Trauma

PROJECT_TITLE: Training in Trauma and Sepsis Research

STUDY_SECTION_NAME: Special Emphasis Panel[ZGM1 TWD-A (PD)]


NIH_SPENDING_CATS: Hematology;Pediatric

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: PROJECT NARRATIVE The Pediatric Hematology and Transfusion Medicine Multidisciplinary Research Training Award (PHTMMRT) at Children's National is a rigorous 2- to 3-year mentored program of career development and research training for post-doctoral pediatric subspeciality trainees who have demonstrated potential for and interest in pursuing research careers particularly in the areas of red cell biology, and sickle cell disease, cell therapies/immunobiology, infection/inflammation and coagulation/vascular biology. The ultimate goal of PHTMMRT is to develop independent clinician-investigators and academic leaders in the scientific domains of relevance to The National Heart, Lung, and Blood Institute.

PI_NAMEs: BOLLARD, CATHERINE M.;LUBAN, NAOMI L (contact)

PROJECT_TITLE: Children's Research Institute Hematology Research Training Grant


NIH_SPENDING_CATS: Physical Injury - Accidents and Adverse Effects

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative Traumatic injury is the leading cause of death for Americans between the ages of 1 and 44, accounting for nearly half of all deaths in this age group, as well as significant long-term complications for many who survive, and the highly-specialized surgical care available at Level 1 trauma centers substantially improves patient survival and recovery from traumatic injury when compared to less specialized treatment. Further advances in the treatment of traumatic injury will require trauma surgeons to actively pursue the research necessary to make new discoveries and develop new systems of care, which is facilitated by adding formal preparation in the methods and application of scientific investigation to their clinical training. The program described herein provides the methodological and experiential groundwork essential for addressing this need.

PI_NAMEs: CAIRNS, BRUCE A (contact);CHARLES, ANTHONY G

PROJECT_TERMS: Fellowship;Trauma Research

PROJECT_TITLE: Trauma Research Fellowship


ORG_CITY: SAINT LOUIS

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Narrative Anesthesiology has an increasing impact on overall patient care and outcomes through a comprehensive perioperative care model. However, anesthesiology research to improve perioperative patient outcomes is limited by the number of well-trained scientists and physicians devoted to anesthesiology research. This T32 program is aimed at increasing the number of well-trained anesthesiology researchers by supporting a formal training program in anesthesiology research at Washington University, which has one of the largest anesthesiology research programs in the US.

PI_NAMEs: AVIDAN, MICHAEL SIMON;EVERS, ALEX S. (contact)

PROGRAM_OFFICER_NAME: PAUL, MOUSHUMI

PROJECT_TITLE: TRAINING PROGRAM IN ANESTHESIOLOGY RESEARCH


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Human Genome;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Prevention;Schizophrenia;Serious Mental Illness

ORG_DEPT: PSYCHIATRY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE “The BrainCellQTL consortium: QTL mapping in the human brain at the single cell level” is a collaborative U24 Center application that integrates and aligns the efforts of four sites (Sage Bionetworks, Seven Bridges, University of Toronto, and Icahn School of Medicine at Mount Sinai) to construct a cell type-specific quantitative trait locus atlas for gene expression and epigenome regulation in the human brain. This resource will be shared with the scientific community and will be extensively utilized to derive genetically driven gene dysregulation in serious mental and neurological disorders.

PI_NAMEs: ROUSSOS, PANAGIOTIS  (contact)

PROGRAM_OFFICER_NAME: PETANCESKA, SUZANA

PROJECT_TERMS: Address;Adopted;Alzheimer's disease related dementia;Alzheimer's disease risk;Area;Atlases;Biological;Brain;brain tissue;Cataloging;Catalogs;causal variant;Cell Nucleus;cell type;Cells;Cellular biology;Clinical Trials;cloud based;cognitive function;Collaborations;Communities;computerized data processing;coping;cost;Data;Data Analyses;Data Commons;Data Element;data harmonization;data platform;Data Set;data sharing;data standards;Disease;Educational workshop;Emotional;empowerment;epigenome;Financial Hardship;Functional disorder;Future;Gene Expression;generalist repository;Generations;Genes;Genetic;Genetic Risk;genetic variant;Genome;genome wide association study;Genotype;Goals;Human;Impairment;insight;Intervention;Lead;Libraries;Link;Linkage Disequilibrium;Machine Learning;Malignant Neoplasms;Maps;medical schools;mental function;Meta-Analysis;Metadata;metadata standards;Methods;Molecular;multiple omics;Multiple Sclerosis;Nerve Degeneration;Nervous System Disorder;neuropsychiatric disorder;Neurosciences;outreach;Parkinson Disease;Pathway interactions;patient stratification;potential biomarker;predictive modeling;Process;Quality Control;Quantitative Trait Loci;Rare Diseases;Regulation;Regulatory Element;Reporting;Reproducibility;Research;Resolution;Resources;Risk;risk mitigation;risk variant;RNA Sequences;Sample Size;Sampling;Schizophrenia;Secure;severe mental illness;single cell sequencing;Site;Structure;Synapses;Taxonomy;Technology;Therapeutic;tool;trait;Transcript;United States National Institutes of Health;Universities;Untranslated RNA;Variant;web portal;webinar;working group


ORG_DEPT: PHYSIOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Due to the increasing pace and complexity of biomedical research advances, there is a greater need than ever before for clinician-scientists who have received the rigorous training that is required to solve important problems in clinical medicine with cutting-edge laboratory research, thereby improving health and enhancing quality of life by reducing disability and death from disease. The goal of the Weill Cornell/Rockefeller/Sloan Kettering Tri- Institutional MD-PhD Program is to identify, train, and mentor a diverse group of outstanding individuals to become effective clinician-scientists and future leaders in biomedical research and patient care.

PI_NAMEs: HSU, KATHARINE C (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: programs

PROJECT_TITLE: Weill Cornell/Rockefeller/Sloan Kettering MST Program

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Data Science;Epilepsy;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative This project will leverage the University of Pennsylvania's open-source platform, Pennsieve, to create an international Epilepsy Data Ecosystem, a resource to accelerate collaborative research on Human Epilepsy. This repository will take in and share high-impact, multi-modal data sets from leading clinical centers and make them easy to discover, share and analyze to improve patient care and develop new technologies. The project replaces ieeg.org, and prospectively take in data from contributors around the world, as a scalable and sustainable repository for epilepsy research.

PI_NAMEs: WAGENAAR, JOOST B (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Ablation;Acceleration;Adopted;Adoption;Affect;Age;Agreement;American;archive data;Archives;Brain;Caring;Charge;Clinical;clinical care;clinical center;cloud based;Collaborations;Communities;community building;Complex;computer science;computerized tools;Data;Data Aggregation;data archive;data ecosystem;data integration;data platform;data repository;Data Scientist;Data Set;data sharing;data standards;data submission;data tools;Database Management Systems;digital;Disease;Educational workshop;Electroencephalography;Engineering;Ensure;Epilepsy;experience;Explosion;Feedback;flexibility;Fostering;Funding;Genetic;Goals;Grant;Human;human data;Image;implantable device;Implanted Electrodes;improved;Infrastructure;Ingestion;International;Internet;Intuition;Lasers;Machine Learning;Medical Records;medical schools;Medicine;meetings;migration;Modeling;multimodal data;Multimodal Imaging;National Institute of Neurological Disorders and Stroke;Neurosciences;Neurosciences Research;new technology;next generation;novel;novel therapeutics;open source;Operative Surgical Procedures;Ownership;Patient Care;Patients;Pennsylvania;personalized intervention;Persons;Pharmaceutical Preparations;Positioning Attribute;programs;prospective;Protocols documentation;Publications;Publishing;Reporting;repository;Research;Research Personnel;Resistance;Resources;Robot;Science;Scientist;Security;sharing platform;Technical Expertise;technology platform;tool;Training;translational impact;Translational Research;United States National Institutes of Health;Universities;Update;Work

PROJECT_TITLE: Pennsieve: Impactful Multimodal Data Sharing for Epilepsy Research


NIH_SPENDING_CATS: Aging;Lung

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE The aging population is increasing at an unprecedented rate at the US and worldwide. Aging impacts the severity and susceptibility of acute and chronic lung disease, however the mechanisms responsible for cellular aging and age-related susceptibility to disease are complex and incompletely understood. This integrated and multidisciplinary training program provides critical and structured guidance for postdoctoral trainees who will be at the forefront advances in biology of aging and pulmonary science.

PI_NAMEs: MALLAMPALLI, RAMA K;MORA, ANA LUCIA (contact)

PROGRAM_OFFICER_NAME: ESPINOZA-PINTUCCI, MARISOL

PROJECT_TERMS: Biology of Aging;Lung Diseases;Training Programs

PROJECT_TITLE: Training Program in the Biology of Aging and Lung Diseases


ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: Project Narrative The Northwestern University Lung Sciences Training Program (NULSTP) will build on its success in training the next generation of physician-scientists and scientists through mentored research that incorporates rigorous training in advanced technologies. The NULSTP trains young investigators to use systems biology models of lung disease derived from patients’ clinical and molecular data to make predictions about disease pathobiology and to causally test these predictions using murine models of disease to advance our goals of reducing the burden of lung disease and promoting lung health. Trainees will continue to publish novel science, attain career development awards, and transition to independent research careers to become future leaders in lung-related translational and basic research.

PI_NAMEs: RIDGE, KAREN M (contact);SZNAJDER, JACOB I

PROGRAM_OFFICER_NAME: REYES, MADELYN

PROJECT_TERMS: Lung;Science;Training Programs

PROJECT_TITLE: Training Program in Lung Sciences

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-X (O1)]


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Behavioral and Social Science

ORG_CITY: TUCSON

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Project Narrative This project uses a three-pronged approach to successfully develop the careers of NIDCD researchers from diverse backgrounds. We aim to create a robust mentoring plan to support newly-hired researchers, to strengthen their skills and build upon the existing support network for mentoring. We will also build the research pipeline by supporting a diverse cohort of undergraduates to work with these faculty members.

PI_NAMEs: ALT, MARY  (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: Academia;Advertising;Advisory Committees;Affect;Attitude;Behavioral;career;Climate;cohort;Color;Communication;Communities;community building;Country;cultural competence;Decision Making;demographics;design;Dimensions;Disincentive;Employee;Ensure;Environment;Equity;evidence base;Exclusion;experience;Extramural Activities;Faculty;faculty support;Failure;Feeling;Fostering;Funding;Goals;Healthcare;Hearing;Hostility;improved;Infrastructure;Institution;Intervention;Investments;Job Satisfaction;Language;Literature;member;Mentors;Methods;mid-career faculty;mosaic;National Institute on Deafness and Other Communication Disorders;next generation;Perception;Persons;Policies;Population;Positioning Attribute;premature;Procedures;Process;Productivity;programs;psychologic;Publications;Published Comment;recruit;Research;Research Personnel;resilience;Resources;Rest;role model;satisfaction;Science;Scientist;skills;Speech;student retention;Students;success;support network;Support System;Taxation;tenure track;tool;Training;undergraduate student;Underrepresented Populations;Work

PROJECT_TITLE: Fostering Underrepresented Employees' Resilience and Zeal for Academia (FUERZA)

STUDY_SECTION_NAME: Special Emphasis Panel[ZDC1 SRB-X (66)]


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: HUNTSVILLE

ORG_NAME: HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY

ORG_STATE: AL

PHR: Project Narrative The human genome has transformed how we study human biology and how we predict and treat human disease, yet learning what all the genome sequences do remains a challenge. This proposal applies high-throughput technologies to map the locations of protein-DNA interactions in human cells, an essential factor in genome function. The data and tools proposed will be a genomic resource crucial for basic research and disease studies.

PI_NAMEs: MENDENHALL, ERIC ;MYERS, RICHARD M (contact)

PROGRAM_OFFICER_NAME: MORRIS, STEPHANIE A

PROJECT_TERMS: 3-Dimensional;Address;Antibodies;ATAC-seq;Basic Science;Binding;Biological Assay;Biology;Catalogs;Cell Differentiation process;Cell Line;cell type;Cells;ChIP-seq;Chromatin;chromatin immunoprecipitation;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Collaborations;Communities;Data;data dissemination;Data Element;data resource;Data Set;Databases;Deposition;Development;Disease;DNA;DNA Binding;DNA Databases;DNA-Protein Interaction;Elements;empowerment;Encyclopedia of DNA Elements;Ensure;Epitopes;experimental study;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Genome;genome editing;Genome Mappings;genome resource;genome-wide;genome-wide analysis;genomic locus;Genomics;Goals;HepG2;high throughput technology;High-Throughput Nucleotide Sequencing;histone modification;Human;Human Biology;human disease;Human Genome;Individual;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Knowledge;Learning;Link;Location;Maps;Measures;member;Modeling;Motivation;Neuronal Differentiation;Neurons;Pattern;Plasmids;Play;precursor cell;Primary carcinoma of the liver cells;Production;Proteins;Reagent;repository;Resources;Role;scale up;Standardization;tool;transcription factor;transcriptome sequencing;two-dimensional;Variant;web interface;Work

PROJECT_TITLE: Expansion of the Human Transcription Factor Genome-wide Binding Map Resource


NIH_SPENDING_CATS: Cancer;Digestive Diseases

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Gastrointestinal cancers constitute the plurality of cancer deaths in the United States, yet there remains a pressing need to train the next generation of scientists to conduct GI cancer research in an innovative and productive manner. Leveraging strong support from Columbia University Irving Medical Center and the Herbert Irving Comprehensive Cancer Center, we have developed a GI Cancer Training Program to identify and recruit a diverse pool of trainees, offer them a rigorous and individualized curriculum, and provide them with research experience in gastrointestinal cancers working with one of our numerous expert and experienced faculty mentor investigators at Columbia University.

PI_NAMEs: ABRAMS, JULIAN  (contact);RUSTGI, ANIL K;RYEOM, SANDRA

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TERMS: Malignant neoplasm of gastrointestinal tract;multidisciplinary;Training

PROJECT_TITLE: Multidisciplinary Training in Gastrointestinal Cancers


ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: Project Narrative Because of the worsening survival of women with advanced and relapsed endometrial cancer, this P01 grant is focused on targeting replication stress (RS) in order to improve therapeutic outcomes in these patients. Each of the 3 projects focuses on different strategies for targeting RS in endometrial cancer: i) using WEE1 inhibition as monotherapy against uterine serous carcinomas (USC) and other p53-mutated uterine cancers characterized by genomic alterations associated with high RS; ii) using combined ATR and PI3K inhibition to capitalize on concomitant PI3K pathway alterations and genomic alterations associated with high RS in USCs and ARID1A mutated uterine carcinomas; and iii) using ATR and WEE1 inhibitors in combination with immune checkpoint inhibitors to facilitate effective anti-tumor immunity in this disease.

PI_NAMEs: KONSTANTINOPOULOS, PANAGIOTIS ;LIU, JOYCE ;MATULONIS, URSULA ANNE (contact)

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: Address;Advocate;Animals;anti-cancer research;Applications Grants;ARID1A gene;Basic Science;biological adaptation to stress;Biological Assay;Biological Markers;Biological Models;Biometry;Biopsy;black women;Boston;cancer cell;Cancer cell line;Carcinoma;checkpoint inhibition;Clinical;Clinical Research;Clinical Trials;Collaborations;Collection;Communication;Communities;Computational Biology;Computer software;CRISPR screen;Dana-Farber Cancer Institute;Data;Data Analyses;Data Collection;Databases;Death Rate;design;Disease;DNA;DNA analysis;DNA biosynthesis;DNA Damage;DNA damage checkpoint;DNA Repair;DNA replication fork;DNA Sequence Alteration;Dose;drug development;Endometrial Carcinoma;Endometrium;Experimental Designs;Experimental Models;experimental study;Genetically Engineered Mouse;Genomic Instability;Goals;Grant;Gynecologic Pathology;Histologic;Hospitals;Human;Immune;Immune checkpoint inhibitor;Immunologics;Immunosuppression;Immunotherapy;improved;improved outcome;In Vitro;in vitro Model;in vivo;Incidence;inhibitor;International;IRF3 gene;kinase inhibitor;Laboratories;Lead;Leadership;Malignant Female Reproductive System Neoplasm;Malignant Neoplasms;Measures;Mediating;member;Methodology;Methods;Mismatch Repair;Modeling;Monitor;multidisciplinary;Mutate;novel strategies;Organoids;Outcome;Pathology;Pathway interactions;patient derived xenograft model;Patients;Phase;Phosphotransferases;PIK3CG gene;Pre-Clinical Model;programs;Protocols documentation;quality assurance;Recurrence;Relapse;replication stress;Reporting;Research;Research Personnel;response;Salvage Therapy;Sampling;Serous;Signal Transduction;statistics;survival outcome;synergism;targeted agent;TBK1 gene;therapy outcome;TP53 gene;Translating;translational progress;Translational Research;Treatment Efficacy;tumor;Tumor Immunity;United States;Uterine Cancer;Uterine Neoplasms;Uterus;Woman;women's outcomes;Work

PROJECT_TITLE: Targeting Replication Stress and DNA Damage Response in Uterine Cancer


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

PHR: PROJECT NARRATIVE: PROJECT 1 – WEE1 inhibition in uterine serous carcinomas or p53-mutated uterine cancers Molecular features of uterine serous carcinoma (USC) and other p53-mutated uterine cancers, a group of uterine cancers with poor prognoses, suggest that these cancers have high “replication stress”, a state where replication of the DNA is slowed and under stress, and may therefore be particularly vulnerable to drugs that target replication stress like a WEE1 inhibitor. A clinical trial with the WEE1 inhibitor adavosertib previously demonstrated significant clinical activity in USCs. In this project, we seek to advance the care and improve outcomes for individuals with USC or p53-mutated uterine cancers by establishing a better understanding of the mechanisms of replication stress and how replication stress is linked to WEE1 inhibitor sensitivity, leveraging assays of replication stress and WEE1 inhibitor sensitivity in patient-derived organoid model systems, immunohistochemical measures of DNA damage and replication stress in mouse model systems, and biopsy samples taken from patients on a clinical trial with the WEE1 inhibitor ZN-c3.

PI_NAMEs: LIU, JOYCE  (contact)

PROJECT_TERMS: Accounting;Area;arm;Ascites;Biological Assay;Biological Markers;Biological Models;biomarker development;Biopsy;Biopsy Specimen;Cancer Patient;cancer surgery;cancer type;Carcinoma;care outcomes;CCNE1 gene;Cell Cycle;Cessation of life;chemotherapy;Clinical;Clinical Sensitivity;Clinical Trials;Data;Development;DNA biosynthesis;DNA Damage;DNA replication fork;Dose;Drug Targeting;effective therapy;Endometrial Carcinoma;ERBB2 gene;Exposure to;FDA approved;Future;Gamma-H2AX;Genetically Engineered Mouse;Genomics;Histologic;improved outcome;In Vitro;in vitro Model;in vivo;in vivo Model;Individual;inhibitor;insight;Institution;investigator-initiated trial;KRAS2 gene;Letters;Link;Malignant Neoplasms;Measures;Microfluidics;Modeling;Molecular;mouse model;Mutate;Mutation;new therapeutic target;next generation sequencing;novel;Oncogenes;Oncogenic;Organoids;patient derived xenograft model;Patients;pembrolizumab;Pharmaceutical Preparations;Pharmacologic Substance;Phase;pre-clinical;Prognosis;Progression-Free Survivals;RB1 gene;Recurrence;Regimen;replication stress;response;Sampling;Serous;Specimen;Speed;Stable Disease;Stress;targeted agent;Testing;The Cancer Genome Atlas;Therapeutic;TP53 gene;Translating;tumor;Uterine Cancer;Uterus

PROJECT_TITLE: Targeting WEE1 in uterine serous or p53-mutated uterine cancer


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Genetics;Human Genome;Orphan Drug;Rare Diseases;Uterine Cancer;Women's Health Research

PHR: Project Narrative Genomic alterations associated with high replication stress (RS) and concomitant PI3K pathway alterations are prevalent in uterine serous and ARID1A-mutated uterine cancers (UC). Based on preliminary data supporting synergistic antitumor activity of combined ATR and PI3K inhibition, this proposal aims to investigate the therapeutic potential and biologic activity of this novel therapeutic strategy in UC, whose incidence and death rates are both significantly increasing in the United States.

PI_NAMEs: KONSTANTINOPOULOS, PANAGIOTIS  (contact)

PROJECT_TERMS: Abbreviations;Address;Affect;ARID1A gene;ATM deficient;ATR gene;Biological;Biological Assay;BRCA deficient;cancer cell;Cancer cell line;Carcinoma;CCNE1 gene;Cell Cycle;Cell Cycle Arrest;Cell Cycle Progression;chemotherapy;Clear Cell;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Collection;CRISPR screen;Data;Death Rate;Defect;design;DNA biosynthesis;DNA Damage;DNA Repair;DNA replication fork;DNA Sequence Alteration;Dose;efficacy study;Event;Exhibits;expectation;Exposure to;FBXW7 gene;Genetically Engineered Mouse;genome-wide;Genomic Instability;Genomics;Histologic;Histology;Human;In Vitro;in vivo;Incidence;inhibitor;Letters;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant neoplasm of prostate;Malignant Neoplasms;Maximum Tolerated Dose;Medical;Mitosis;Modeling;Molecular;Mutate;Mutation;Myelosuppression;novel;novel therapeutic intervention;novel therapeutics;open label;Organoids;Pathway interactions;patient derived xenograft model;Patients;Phase;Phase Ib Trial;Phosphotransferases;PIK3CG gene;Prevalence;Recommendation;Recurrence;replication stress;Research;research clinical testing;response;screening;Serous;synergism;Therapeutic;therapeutically effective;Treatment Protocols;tumor;United States;Uterine Cancer;Uterine Neoplasms;Uterus

PROJECT_TITLE: Combined ATR and P13k inhibition in uterine cancer


NIH_SPENDING_CATS: Cancer;Clinical Research;Genetics;Immunotherapy;Uterine Cancer;Women's Health Research

PHR: Project Narrative While the combined pembrolizumab and lenvatinib has been an approved treatment for recurrent MSS/MMRP uterine cancers (UCs), adverse effects are a major challenge in the clinic and many patients do not respond to this regimen. Given that most MSS/MMRP UCs are associated with high degree of replication stress (RS), we hypothesize that DNA damage checkpoint kinase inhibitors (e.g. ATRi and WEE1i) will increase RS-associated DNA damage to not only induce tumor cells’ synthetic lethality but also engage DNA sensing STING pathway activation to enhance anti-tumor immunity to improve the therapeutic outcome for UCs. The main goal of the project it to investigate integration of DNA damage checkpoint kinase inhibition and immune checkpoint inhibition to provide mechanistic and preclinical proof-of-concept to support clinical translation of this therapeutic strategy for patients with MSS/MMRP UC, an area of tremendous unmet need.

PI_NAMEs: ZHAO, JEAN  (contact)

PROJECT_TERMS: adaptive immunity;Adverse effects;Allografting;Area;cancer cell;Cancer cell line;candidate identification;candidate marker;Carcinoma;checkpoint inhibition;Clinic;Clinical;clinical translation;Clinical Trials;Coculture Techniques;combinatorial;CTLA4 blockade;Cytotoxic agent;Cytotoxic Chemotherapy;Data;Dendritic Cells;DNA;DNA Damage;DNA damage checkpoint;DNA Integration;DNA Sequence Alteration;Dose;effective therapy;Endometrioid Tumor;Evaluation;Experimental Designs;FDA approved;Genes;Goals;Human;human model;Humor;Immune;Immune checkpoint inhibitor;Immunocompetent;Immunologics;Immunosuppression;Immunotherapy;improved;in vivo;inhibitor;insight;Interferons;Interruption;IRF3 gene;kinase inhibitor;Lead;Malignant Neoplasms;Medical;Microsatellite Repeats;Mismatch Repair;Mismatch Repair Deficiency;Modeling;Modification;mouse model;Mus;Mutate;Natural Immunity;neoplastic cell;novel strategies;Organoids;Pathway interactions;patient population;Patients;PD-1 blockade;pembrolizumab;Phosphotransferases;PIK3CG gene;Polymerase;pre-clinical;Prevalence;Primary Neoplasm;Recurrence;Regimen;replication stress;response;Salvage Therapy;Sampling;Schedule;Serious Adverse Event;Serous;Signal Transduction;Specimen;System;targeted agent;TBK1 gene;Testing;The Cancer Genome Atlas;Therapeutic;therapy outcome;Tissues;Toxic effect;translational therapeutics;Treatment Efficacy;tumor;Tumor Immunity;tumor-immune system interactions;Update;Uterine Cancer;Uterus;Work

PROJECT_TITLE: Targeting replication stress to engage DNA sensing STING pathway derived anti-tumor immunity to improve the therapeutic outcomes in uterine cancer


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

PHR: Project Narrative The Administrative Core of this P01 Program will help meet the public health goals of the NCI by studying replication stress in uterine cancer and devising new therapeutic strategies for women with uterine cancer. Uterine cancer incidence is rising in the United States, survival is decreasing, there is a rise in the incidence of non-endometrioid cancers, and additionally, survival of black women with endometrial cancer is significantly worse than non-black women (www.seer.gov). The goals of this P01 application are to improve outcomes for women with advanced and relapsed endometrial cancer by exploiting replication stress in endometrial cancer.

PI_NAMEs: MATULONIS, URSULA ANNE (contact)

PROJECT_TERMS: Accountability;Advocate;black women;Cancer Center;Clinical Research;Clinical Trials;Collaborations;Communication;DNA Damage;Endometrial Carcinoma;Ensure;experimental study;Goals;Grant;health goals;Hospitals;improved outcome;Incidence;Information Dissemination;Leadership;Malignant Neoplasms;meetings;Monitor;novel therapeutic intervention;Office of Administrative Management;Principal Investigator;Program Research Project Grants;programs;Public Health;Publications;Relapse;replication stress;Reporting;Research Personnel;Resources;response;Schedule;Structure;Supervision;Translational Research;United States;Uterine Cancer;Woman;women's outcomes

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Genetics;Immunotherapy;Precision Medicine;Uterine Cancer;Women's Health Research

PHR: PROJECT NARRATIVE Endometrial cancers carry genomic features of replication stress and endogenous DNA damage that may make them susceptible to treatments that induce further replication stress above a lethal threshold. Projects in this proposal will study WEE1 and ATR inhibitor-based treatments in organoid and mouse models, and in clinical trials. The Pathology Core will offer histologic quality control for model development, conduct immunohistochemistry for predictive and pharmacodynamic markers related to DNA damage, replication stress and DNA repair, and oversee multiplex immunofluorescence for interrogation of the immune microenvironment, in order to identify subsets of patients likely to benefit from these treatments and to determine if response is related to the activation of innate immunity. The Core will bring expertise in Gynecologic Pathology and DNA Repair to the entire endeavor of studying replication stress in endometrial cancers to reduce the burden of this disease and to improve patient outcomes.

PI_NAMEs: SHAPIRO, GEOFFREY I (contact)

PROJECT_TERMS: Aftercare;ARID1A gene;ATM deficient;Biological Assay;Biological Markers;biomarker development;burden of illness;cancer diagnosis;CCNE1 gene;Clinical;Clinical Trials;Data;DNA analysis;DNA biosynthesis;DNA Damage;DNA Repair;Endometrial Carcinoma;Ensure;experience;Experimental Designs;Experimental Models;experimental study;Genomics;Goals;Gynecologic;Gynecologic Pathology;Histologic;homologous recombination;Human;Human Resources;immune checkpoint;Immunofluorescence Immunologic;immunohistochemical markers;Immunohistochemistry;Immunooncology;improved;inhibitor;Mediating;Methods;model development;Modeling;mouse model;Mus;mutant;Natural Immunity;Neoplasms;Oncogene Activation;Organoids;Outcome;Pathologist;Pathology;Pathway interactions;patient derived xenograft model;patient subsets;Patient-Focused Outcomes;pharmacodynamic biomarker;PIK3CG gene;pre-clinical;predicting response;predictive marker;Predisposition;Primary Neoplasm;Program Research Project Grants;protein expression;Proteins;PTEN gene;Quality Control;recombinational repair;Relapse;replication stress;Research;response;Sampling;Scientist;Serous;Services;Standardization;Stimulator of Interferon Genes;T cell infiltration;therapeutic target;Tissue Banks;Tissues;TP53 gene;transcriptome sequencing;tumor;Tumor Immunity;tumor-immune system interactions;Uterine Cancer;Uterus;Variant;Woman;Work;WT1 gene

PROJECT_TITLE: Pathology Core


NIH_SPENDING_CATS: Bioengineering;Cancer;Uterine Cancer;Women's Health Research

PHR: PROJECT NARRATIVE The Biostatistics and Computational Biology Core will provide statistical, bioinformatic and computational consultation and in-depth collaboration to the P01 research program in the areas of planning, design, conduct, analysis, and reporting of laboratory experiments, and clinical trials. Having a dedicated group of biostatisticians and computational biologists with expertise in therapeutic cancer clinical trials will ensure the best possible designed studies to answer scientific questions of interest related to targeting replication stress in endometrial cancer.

PI_NAMEs: TAYOB, NABIHAH  (contact)

PROJECT_TERMS: Address;Animals;anti-cancer research;Area;Bioinformatics;bioinformatics pipeline;Biological;Biometry;Biostatistics Core;cancer clinical trial;Clinical;Clinical Research;Clinical Trials;Clinical Trials Design;Collaborations;Communities;Complex;Computational Biology;Computer software;Consultations;Correlative Study;Data;Data Analyses;Data Collection;data integrity;Databases;Dedications;design;Development;DNA Damage;Drug Combinations;Endometrial Carcinoma;Ensure;experimental arm;Experimental Designs;experimental study;interest;Laboratories;laboratory experiment;member;Methodology;Methods;Monitor;Outcome;Pathology;Pre-Clinical Model;preclinical study;Program Research Project Grants;programs;quality assurance;Quality Control;replication stress;Reporting;Research;Research Design;Research Personnel;response;Role;Sampling;Statistical Data Interpretation;Statistical Methods;Statistical Models;statistics;Therapeutic;Translational Research;Uterine Cancer;Variant;Work

PROJECT_TITLE: Bio statistics Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Genetics;Orphan Drug;Ovarian Cancer;Rare Diseases;Uterine Cancer;Women's Health Research

PHR: PROJECT NARRATIVE: CORE 3 – PRECLINICAL MODELING Certain endometrial cancers have molecular characteristics that suggest the presence of high replication stress and potential sensitivity to agents that can further induce further replication stress. Pre-clinical models provide valuable insights into the biology, mechanism, and potential efficacy of therapeutic strategies and combinations. The Preclinical Modeling Core will generate, maintain, and characterize a collection of patient-derived xenograft (PDX) models, patient-derived organoid (PDO) cultures, and genetically engineered mouse models (GEMMs) of uterine cancer to support the proposed projects studying the effects of WEE1 and ATR-targeted strategies on replication stress, tumor viability, and immune microenvironment, with the overall goal of identifying new therapies and improving outcomes for individuals with uterine cancer.

PROJECT_TERMS: Biology;Biopsy;Cancer cell line;Cancer Patient;Carcinoma;Cell Line;Cells;Characteristics;Clinical;clinically relevant;Collaborations;Collection;Data;design;Development;Disease;DNA Damage;Doctor of Philosophy;Endometrial Carcinoma;experience;Experimental Designs;Experimental Models;Generations;Genetic;Genetically Engineered Mouse;Genomics;Goals;Grant;Histologic;Human;human disease;Implant;improved outcome;Individual;Infrastructure;insight;Investigation;Lead;Maintenance;Malignant Breast Neoplasm;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Measures;Medical Oncologist;model design;Modeling;Molecular;Mutate;next generation sequencing;novel therapeutic intervention;novel therapeutics;Organoids;Paracentesis;Parents;Pathology;Pathway interactions;patient derived xenograft model;Patients;PIK3CG gene;Pre-Clinical Model;Primary Neoplasm;Program Research Project Grants;replication stress;repository;Research;response;Role;Sampling;Serous;Stimulator of Interferon Genes;System;targeted agent;Therapeutic procedure;therapy outcome;Thoracentesis;TP53 gene;Treatment Efficacy;tumor;Tumor Immunity;tumor-immune system interactions;Uterine Cancer;Uterus;Woman;Work;Xenograft Model

PROJECT_TITLE: PDX Modeling Core


ORG_CITY: ATLANTA

ORG_DEPT: CHEMISTRY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative This application requests funding to support a new predoctoral training program at Emory University, focused on providing specialized, interdisciplinary training to students working at the critical intersection of chemistry, biology, and human health, with a particular emphasis on drug discovery and development. Through the construction of a diverse cohort and unique training plan, we aim to equip trainees with the knowledge, creativity, and motivation to solve significant problems in chemical biology, drive therapeutic innovation, and succeed in diverse careers in the biomedical workforce.

PI_NAMEs: BLAKEY, SIMON B. (contact);HESS, ELLEN J.

PROJECT_TITLE: Biological Discovery through Chemical Innovation Training Program at Emory University


ORG_CITY: LOS ANGELES

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: PROJECT NARRATIVE The mission of the UCLA-Caltech Medical Scientist Training Program is to recruit and train a diverse group of outstanding physician-scientists committed to becoming leaders, educators, and innovators in our nation’s biomedical research workforce. Through their clinical and research training and understanding of human health and disease, these individuals are poised to make impactful contributions to technology innovation and growth of knowledge at the intersection of science and medicine to the greater benefit of public health.

PI_NAMEs: AJIJOLA, OLUJIMI A;DAWSON, DAVID WAYNE (contact)

PROJECT_TERMS: Medical;Scientist;Training Programs


ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Overall Project Narrative This SPORE is dedicated to improving outcomes from prostate cancer, which affects 1 in 8 men in the United States, by delivering three new approaches to prostate cancer treatment. Over the planned 5 years of funding, three new combinatorial treatment strategies will be evaluated in clinical trials and in correlative laboratory-based studies to assess their effectiveness in men with prostate cancer.

PI_NAMEs: DENMEADE, SAMUEL R (contact);LUPOLD, SHAWN

PROGRAM_OFFICER_NAME: SCROGGINS, BRADLEY TODD

PROJECT_TERMS: Acceleration;addiction;Affect;American;Androgen Receptor;anti-cancer research;Award;Biology;cancer diagnosis;Cancer Etiology;Cancer Research Project;career;Castration;Center for Translational Science Activities;Characteristics;Clinical Trials;Collection;combinatorial;Combined Modality Therapy;Comprehensive Cancer Center;Cytotoxic Chemotherapy;Dedications;Detection;Development;Disease;Disease Resistance;DNA;DNA Repair;DNA Repair Pathway;Dose;Effectiveness;effectiveness evaluation;Environmental Health;Epidemiology;epigenetic drug;Equipment;Funding;Future;Gene Modified;Genomics;Goals;Homeostasis;Hormonal;hormone therapy;Human;imaging modality;Immune;Immune system;Immunotherapeutic agent;Immunotherapy;improved;improved outcome;Infrastructure;innovation;insight;Institution;Knowledge;Laboratories;Leadership;Life;Malignant neoplasm of prostate;Manuscripts;medical schools;men;Mentors;Metastatic Prostate Cancer;Methods;Modality;Modeling;Modernization;Molecular;molecular imaging;molecular marker;Morbidity - disease rate;mortality;Mutation;novel strategies;Oncology;Pathology;Pathway interactions;Peer Review;Phase II Clinical Trials;Play;Poly(ADP-ribose) Polymerase Inhibitor;Positioning Attribute;Productivity;Prognosis;programs;Prostate;prostate cancer cell;prostate cancer prevention;prostate cancer risk;Prostate Cancer therapy;Public Health Schools;Publications;Radiation Oncology;Radiology Specialty;Reagent;Receptor Signaling;recruit;Research;Research Personnel;Research Project Grants;Resistance;Resources;Risk Assessment;Role;Safety;Screening for Prostate Cancer;small molecule;success;Talents;Techniques;Technology;Testing;Testosterone;Therapeutic;Translating;translational cancer research;Translational Research;translational scientist;treatment strategy;tumor-immune system interactions;United States;Universities;Urology;Vaccines

PROJECT_TITLE: SPORE in Prostate Cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RPRB-8 (O1)]


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

PI_NAMEs: DENMEADE, SAMUEL R (contact)

PROJECT_TERMS: Advocate;anti-cancer research;Applications Grants;Basic Science;Cancer Center;career;Caring;Clinical Research;Collaborations;Communication;Communities;Comprehensive Cancer Center;design;Development;Discipline;Ensure;Evaluation;Funding;Goals;Individual;Institution;International;Leadership;Malignant neoplasm of prostate;Malignant Neoplasms;Medical;medical schools;Monitor;National Cancer Advisory Board;National Cancer Institute;Principal Investigator;Productivity;programs;Prostate;Public Health;Research;Research Activity;Research Personnel;Research Project Grants;Resources;response;Schools;Services;skills;Structure;Talents;Teleconferences;Transcend;Translational Research;translational scientist;Travel;United States National Institutes of Health;Universities


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Prostate Cancer;Urologic Diseases

PHR: PROJECT 1 - PROJECT NARRATIVE This proposal tests the safety and efficacy of combined therapeutic suppression of MYC expression through combination therapy with BAT and the MYC-suppressing bromodomain inhibitor ZEN-3694 in sequence with enzalutamide as therapy for men with CRPC progression on abiraterone. Further, it evaluates mechanisms of adaptation to this therapy, explores the effect of this therapy on activating the immune microenvironment, and describes strategies to develop biomarkers of response and resistance. The goal of these innovative studies is to generate proof-of-concept clinical data that could lead to a fundamental change in the way we administer hormonal therapy that could enhance long-term survival and improve quality of life for men with prostate cancer.

PROJECT_TERMS: abiraterone;Ablation;Aftercare;American;androgen deprivation therapy;Androgen Receptor;Androgen Therapy;Androgens;AR gene;Area;arm;ATAC-seq;Automobile Driving;Biopsy;Biopsy Specimen;Bromodomain;Bromodomains and extra-terminal domain inhibitor;c-myc Genes;Castration;Cell Death;cell killing;Cell model;Cell Nucleus;cell type;Cells;Chromatin;Chronic;Clinical;Clinical Data;clinical development;clinical predictors;Clinical Research;combat;combinatorial;Combined Modality Therapy;Cytoplasm;Data;deprivation;Disease;Dose;Down-Regulation;Environment;enzalutamide;Exposure to;Gene Amplification;Gene Dosage;Gene Expression;Genes;Genetic Transcription;Goals;Growth;hormone therapy;Human;Immunohistochemistry;improved;inhibitor;innovation;Laboratory Study;Lesion;Lymph;lymph node biopsy;lymph nodes;Malignant neoplasm of prostate;Measurable;men;Metastatic Prostate Cancer;MYC Family Protein;MYC gene;neoplastic cell;Nuclear;overexpression;Patient Representative;patient response;patient stratification;Patients;Pattern;Phase;Play;potential biomarker;pre-clinical;Pre-Clinical Model;preclinical study;predicting response;pressure;prevent;primary endpoint;programs;Progression-Free Survivals;Proliferating;prostate cancer cell;protein expression;Proteins;Quality of life;radiological imaging;Randomized;Reader;receptor expression;Receptor Signaling;Resistance;Resistance development;Resources;responders and non-responders;response;response biomarker;Role;Safety;safety testing;Serum;Sex Functioning;Signal Transduction;single cell ATAC-seq;Stains;Testing;Testosterone;Therapeutic;therapy resistant;Time;Tissue-Specific Gene Expression;transcriptome sequencing;treatment response;tumor;tumor DNA;tumor microenvironment;tumor-immune system interactions;Up-Regulation

PROJECT_TITLE: Project 1: Combined Suppression of MYC as therapy for CRPC: the COSMYC trial


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

PHR: PROJECT 2 - PROJECT NARRATIVE Immunotherapy–the use of a person’s own immune system—to target and kill melanoma, lung, and colon cancer has resulted in unprecedented advances in treatment. However, in PCa immune-checkpoint blockade utilizing anti-CTLA-4 or anti-PD1 antibodies has yielded minimal clinical activity to date, as these pathways may not be primary checkpoints in PCa. In the described clinical trial herein we are investigating the anti-tumor, immunological and biological effects of B7-H3 +/- ADC chemotherapy in men with metastatic castrate resistant prostate cancer utilizing Enoblituzumab (a humanized monoclonal antibody against B7-H3) and MGC018 (a duocarmycin-containing humanized antibody-drug conjugate (ADC) that also binds non-competitively to B7-H3).

PI_NAMEs: PIENTA, KENNETH J. (contact)

PROJECT_TERMS: advanced disease;adverse outcome;Affinity;Aftercare;androgen independent prostate cancer;anti-CTLA4;anti-PD1 antibodies;anti-tumor immune response;antibody-dependent cell cytotoxicity;Antibody-drug conjugates;antigen-specific T cells;Apoptosis;arm;Binding;Biochemical;Biological;Biopsy Specimen;Bladder;Cancer Etiology;Cancer Model;Cancer Patient;CD276 gene;CD8B1 gene;Cell Density;Cell Proliferation;Cells;Cessation of life;chemotherapy;Clinical;clinical efficacy;Clinical Trials;Colon Carcinoma;Combination immunotherapy;CTLA4 gene;cytotoxic;cytotoxicity;density;Development;digital;Dose;Duocarmycin;Epitopes;experience;first-in-human;FOXP3 gene;functional status;Future;Gene Expression;Granzyme;hormone therapy;Hormones;humanized antibody;humanized monoclonal antibodies;Immune;immune checkpoint;immune checkpoint blockade;Immune system;Immunity;Immunologics;Immunotherapy;Interferon Type II;Kidney;Lung;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Measures;Mediating;Melanoma;member;men;Metastatic Melanoma;Metastatic/Recurrent;Monoclonal Antibodies;mRNA Expression;mutation assay;Myelogenous;Myeloid Cells;nano-string;Natural Killer Cells;neoantigens;neoplastic cell;novel;Pathologic;Pathway interactions;Patients;Peripheral;Persons;Pharmacodynamics;Phase II Clinical Trials;Population;pre-clinical;Prognosis;programmed cell death ligand 1;programmed cell death protein 1;Progression-Free Survivals;prostate cancer progression;Prostatectomy;Prostatic Neoplasms;Proteomics;radiological imaging;Randomized;Refractory Disease;Regulatory T-Lymphocyte;Research Personnel;response;Role;Safety;secondary endpoint;spatial integration;T cell receptor repertoire sequencing;T cell response;T-Lymphocyte;targeted treatment;Testing;therapeutic target;transcriptome sequencing;transcriptomics;Treatment Efficacy;tumor;Tumor Antigens;tumor microenvironment;virtual;VTCN1 gene

PROJECT_TITLE: Project 2: Dual Targeting of B7-H3 in mCRPC


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Prostate Cancer;Urologic Diseases

PHR: PROJECT NARRATIVE Inhibitors of the Poly-ADP Ribose Polymerase (PARP) enzymes have recently proven to be effective for treatment of metastatic castration resistant prostate cancer (mCRPC) in a minority of patients that harbor mutations in specific DNA homologous repair genes. However, these drugs are not effective in the majority of prostate cancers without such DNA repair gene mutations. Here, we develop a novel combination therapeutic approach comprised of an epigenetic drug targeting DNA methyltransferase enzymes combined with a second drug targeting PARP enzymes to induce synthetic lethality in mCRPC lacking underlying homologous repair mutations, thereby expanding the utility of PARP inhibitors for the majority of men with mCRPC.

PI_NAMEs: YEGNASUBRAMANIAN, SRINIVASAN  (contact)

PROJECT_TERMS: abiraterone;advanced prostate cancer;androgen independent prostate cancer;anti-cancer;anti-tumor immune response;Apoptotic;Biology;biomarker driven;brca gene;BRCA mutations;BRCA1 gene;BRCA1 Mutation;BRCA2 gene;BRCA2 Mutation;cancer cell;Cancer Patient;cancer subtypes;Castration;Cell Death;Cell Line;Chemicals;Chromatin;Clinical Trials Design;Combined Modality Therapy;Coupled;Data;Decitabine;Defect;DNA;DNA Damage;DNA Methyltransferase Inhibitor;DNA Modification Methylases;DNA Repair Disorder;DNA Repair Gene;DNA Sequence Alteration;Down-Regulation;Drug Targeting;effective therapy;Enzymes;epigenetic drug;Epigenetic Process;epigenetic therapy;Exhibits;Future;Gene Mutation;gene repair;Generations;Genetically Engineered Mouse;Genomic approach;Genomics;Genotype;Growth;homologous recombination;homologous recombination deficiency;hormone therapy;Immune response;Immunocompetent;immunogenic;improved;In Situ;In Vitro;in vitro Model;in vivo;in vivo Model;inhibitor;innovation;Interferons;liquid biopsy;Malignant neoplasm of prostate;Mediating;men;men's group;Minority;molecular phenotype;mouse model;Mus;mutant;Mutate;Mutation;novel;novel strategies;novel therapeutic intervention;objective response rate;Oral;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;pharmacodynamic biomarker;Pharmacodynamics;Phase;Phase 1/1b Clinical Trial;Poly(ADP-ribose) Polymerase Inhibitor;Poly(ADP-ribose) Polymerases;Population;Pre-Clinical Model;Progression-Free Survivals;prostate cancer model;repaired;Reporting;Resistance;response;Role;Safety;safety assessment;Signal Transduction;synergism;Testing;Therapeutic;Therapeutic Index;therapeutically effective;Toxic effect;tumor

PROJECT_TITLE: Project 3: Induction of synthetic lethality with combined DNMT and PARP inhibition