NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Childhood Leukemia;Data Science;Genetics;Hematology;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Narrative This project focuses on understanding how patients develop Acute Myeloid Leukemia and developing new therapies to treat them. Each of these goals requires taking “big data” from experiments and applying computer programs and statistics that help to draw conclusions and generate new hypotheses about this deadly disease. Dr. Miller is an expert in doing so and has key experience in the genomics of AML, and this award will support his contributions to the project.

PI_NAMEs: MILLER, CHRISTOPHER A (contact)

PROGRAM_OFFICER_NAME: DUGLAS TABOR, YVONNE

PROJECT_TERMS: Acute Myelocytic Leukemia;Algorithm Design;algorithm development;Area;Award;Big Data;Bioinformatics;Biology;Cell Physiology;computer program;Creativeness;dark matter;Data Set;Disease;DNMT3a mutation;epigenome;epigenomics;Event;experience;experimental study;fitness;Genetic Transcription;Genome;genome sequencing;Genomics;Goals;Hematopoietic stem cells;Informatics;Intuition;Knowledge;leukemic transformation;metaplastic cell transformation;Modeling;Molecular;molecular targeted therapies;Mutation;neoplastic cell;new technology;novel;novel therapeutic intervention;novel therapeutics;Patients;Phenotype;Productivity;programs;Research;Role;Statistical Models;statistics;targeted treatment;Training;tumor;Untranslated RNA;Variant;whole genome

PROJECT_TITLE: Comprehensive Informatic Analyses of AML Genomes and Epigenomes


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PI_NAMEs: BATCHELOR, TRACY T (contact)

PROJECT_TERMS: Address;Adolescent;Adult;Adult Glioma;Agar;Anabolism;Apoptosis;Astrocytoma;Basic Science;Biological Markers;Biology;Brain;Branched-Chain Amino Acids;Catabolism;Cell Differentiation process;Cells;Central Nervous System Neoplasms;Classification;Clinic;Clinical;clinical material;clinical translation;Clinical Trials;cohort;Collection;Combined Modality Therapy;Defect;Dependence;Diffuse;Dihydroorotate dehydrogenase;Dihydroorotate Dehydrogenase Inhibitor;Disease;DNA analysis;DNA Damage;Drug Targeting;effective therapy;Eligibility Determination;Enzymes;Excision;FDA approved;Foundations;Future;gain of function;Genes;Genomics;Glioblastoma;Glioma;Gliomagenesis;Glutamates;Glutaminase;Glutathione;Goals;Human;human subject;Image;Immunohistochemistry;In Vitro;inhibitor;Isocitrate Dehydrogenase;Knowledge;liquid chromatography mass spectrometry;Magnetic Resonance Spectroscopy;Malignant - descriptor;Malignant Glioma;Malignant Neoplasms;mass spectrometric imaging;Medical;Metabolic;Methods;Modeling;Molecular;Monitor;mutant;Mutation;new therapeutic target;Newly Diagnosed;novel;novel therapeutic intervention;novel therapeutics;Nucleotide Biosynthesis;nucleotide metabolism;Oncogenes;Oncoproteins;Operative Surgical Procedures;participant enrollment;Pathway interactions;patient population;Patients;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacotherapy;Phase;phase 2 study;pre-clinical;Process;programs;Property;Pyrimidine;Pyrimidine Nucleotides;Radiation;rational design;Recurrence;Research;Research Personnel;Resected;Resistance;response;Safety;screening;single-cell RNA sequencing;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;standard care;stem-like cell;synthetic lethal interaction;targeted treatment;Technology;Testing;Tissue Sample;Translating;tumor;Tumor-Derived;United States;Work;World Health Organization

PROJECT_TITLE: Targeting metabolic vulnerabilities in Astrocytoma, IDH-mutant, Grade 4


NIH_SPENDING_CATS: Cancer;Clinical Research;Colorectal Cancer;Dietary Supplements;Digestive Diseases;Liver Cancer;Liver Disease;Nutrition;Obesity;Prevention;Rare Diseases;Women's Health Research

PHR: PROJECT NARRATIVE Evidence collectively implicates visceral adiposity and its closely related metabolic dysregulation as a causal driver of obesity-related colorectal and liver cancers. Inflammation has been proposed as a mediating factor, but the precise inflammatory pathways that best describe the metabolically unhealthy obese state are unknown, warranting well-phenotyped large prospective cohort studies Thus, novel approaches for distilling the inflammatory pathways and markers to identify those most reflective of the metabolically unhealthy obese state have immense potential to uncover key mechanisms and inform powerful broad-spectrum strategies for preventing these cancers.

PI_NAMEs: GIOVANNUCCI, EDWARD ;TOBIAS, DEIRDRE KAY (contact);ZHANG, XUEHONG

PROGRAM_OFFICER_NAME: SIMONDS, NAOKO ISHIBE

PROJECT_TERMS: Address;Adipose tissue;Adult;biobank;Biological;Blood;Blood specimen;Body mass index;C-reactive protein;cancer risk;case control;Chronic;Cocoa Powder;cohort;Cohort Studies;Colorectal;Colorectal Cancer;Communities;cost;Data;Derivation procedure;Development;Diagnosis;Dual-Energy X-Ray Absorptiometry;Eligibility Determination;Ensure;epidemiology study;Ethnic Origin;Exclusion;Follow-Up Studies;Future;Gene Expression;General Population;Genes;Genotype-Tissue Expression Project;Glycosylated hemoglobin A;Goals;Health;Health Professional;high risk;high risk population;Inflammation;Inflammation Process;Inflammatory;innovation;Insulin Resistance;Link;Lipoproteins;Liver;Longitudinal cohort;Longterm Follow-up;Lung;Machine Learning;Malignant neoplasm of liver;Malignant Neoplasms;Measures;Mediating;Mediator;men;Mendelian randomization;Metabolic;Modeling;Multivitamin;novel;novel strategies;Nurses' Health Study;Obesity;Omega-3 Fatty Acids;Organ;Outcome Study;Ovarian;Pathway interactions;Pattern;Phenotype;Physicians;Population Study;prevent;Prevention strategy;Preventive;programs;prospective;Prospective cohort;Prospective, cohort study;Prostate;Proteins;Proteomics;public database;Public Health;Race;Recording of previous events;Regulatory Element;reproductive;Research Personnel;Resources;Risk;Risk Factors;risk prediction;Role;success;Techniques;therapeutic target;Tissues;trait;Validation;Visceral;Vitamin D;Woman;Women's Health;Work

PROJECT_TITLE: Decoding mechanisms underlying metabolic dysregulation in obesity and digestive cancer risk


NIH_SPENDING_CATS: Cancer;Immunotherapy

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative A key class of drug, termed PI3 Kinase inhibitors, has proved effective for tumors driven by oncogenes and growth factor receptors but ineffective for tumors driven by loss of the tumor suppressor called PTEN. Work in this grant will determine the mechanisms underlying this defect and devise ways to correct the problem.

PI_NAMEs: ROBERTS, THOMAS M (contact)

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: Adaptor Signaling Protein;BCAR1 gene;Binding Proteins;Cells;Clinic;Clinical;Combined Modality Therapy;CRKL gene;CRKL protein;Data;Defect;Dependence;Drug Targeting;Effectiveness;Event;Family;Family member;Feedback;Grant;Growth Factor Receptors;Guanosine Triphosphate Phosphohydrolases;immune checkpoint;immune checkpoint blockade;In Vitro;in vivo;inhibitor;Malignant Neoplasms;Membrane Microdomains;Molecular;novel drug combination;Oncogenes;Pharmaceutical Preparations;Phosphatidylinositide 3-Kinase Inhibitor;Phosphatidylinositols;PIK3CG gene;Protein Isoforms;Proteins;PTEN gene;Resistance;response;Signal Transduction;synergism;Testing;tumor;Tumor Suppressor Proteins;Work

PROJECT_TITLE: Maximizing the Effectiveness of PI3K Inhibitors in the Treatment of Pten null Cancers


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Neurosciences;Orphan Drug;Rare Diseases

PI_NAMEs: ECK, MICHAEL J (contact)

PROJECT_TERMS: Adult;Basic Science;Binding;Biochemical;Biological Assay;Brain;Clinical;clinical development;clinical effect;clinical material;clinical translation;Clinical Trials;Collaborations;Dana-Farber Cancer Institute;dimer;Dimerization;Disease;Dose;Dose Limiting;drug development;Drug Kinetics;effective therapy;efficacy study;EGF gene;EGFR gene;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;epidermal growth factor receptor VIII;Exhibits;experience;Failure;first-in-human;Gastrointestinal tract structure;Generations;Genetic;Genetically Engineered Mouse;Genomics;Glioblastoma;Grant;Image;Industry;inhibitor;Knock-out;Letters;Ligands;Malignant neoplasm of lung;mass spectrometric imaging;Maximum Tolerated Dose;Medicine;Molecular;Molecular Conformation;monomer;Mus;mutant;Mutate;Mutation;Neurosphere;new therapeutic target;Non-Small-Cell Lung Carcinoma;novel;Oncogenes;Operative Surgical Procedures;Oral;Oral Administration;Patients;Penetrance;Pharmaceutical Chemistry;Pharmacodynamics;pharmacologic;Pharmacologic Substance;Phase;Phosphotransferases;Plasma;pre-clinical;programs;Property;receptor;Receptor Inhibition;Receptor Signaling;Recurrence;Resistance;Safety;Signal Transduction;single cell sequencing;Skin;small molecule;small molecule inhibitor;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;stem;Structure;Testing;Therapeutic;Tissues;Toxic effect;tumor;tumor heterogeneity;Tyrosine Kinase Domain;Tyrosine Kinase Inhibitor;Variant;Work;Xenograft Model

PROJECT_TITLE: Small molecule inhibitors with a therapeutic window for EGFR signaling variants in glioblastoma


PI_NAMEs: MONJE-DEISSEROTH, MICHELLE  (contact)

PROJECT_TERMS: Acute;Adult;Adult Glioblastoma;Amino Acid Transporter;AMPA Receptors;Attention;Brain;Calcium;Catheters;Cell Proliferation;Cell secretion;Cells;Clinical;Clinical Trials;Coculture Techniques;Communication;Coupled;Data;Drug Targeting;Electrocorticogram;Electrophysiology (science);Excision;extracellular;feeding;Funding;Gap Junctions;Genomics;Glioblastoma;Glioma;Glutamate Receptor;glutamatergic signaling;Glutamates;Grant;Growth;Growth Factor;Hour;Human;human subject;human tissue;Image;improved outcome;in vivo;Infiltration;Magnetic Resonance;Malignant Neoplasms;mass spectrometric imaging;Measures;Mediating;Microdialysis;Modeling;Monitor;mouse model;Mus;Nervous System;Nervous System Disorder;neural circuit;neuroligin 3;neuronal excitability;Neurons;neuropsychiatric disorder;Neurosciences;neurosurgery;new therapeutic target;Oncology;Operative Surgical Procedures;paracrine;Pathogenesis;Pathogenicity;Patients;Perioperative;Pharmaceutical Preparations;pharmacologic;Pharmacologic Substance;Phase;Phosphorylation;Potassium;pre-clinical;Pre-Clinical Model;preclinical study;presynaptic;programs;Progression-Free Survivals;Proliferating;Property;Proteins;Randomized;Recurrence;Reporter;repository;Resected;reuptake;Role;Signal Transduction;single nucleus RNA-sequencing;skills;Slice;Spectrometry;Synapses;synaptic function;Testing;Therapeutic;tissue biomarkers;Tissues;Toxic effect;tumor;tumor microenvironment;tumor progression;Tumor Tissue;two-photon;United States National Institutes of Health;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Targeting the neuronal microenvironment in glioblastoma


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: PHILADELPHIA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

ORG_STATE: PA

PHR: PROJECT NARRATIVE: Advances in the new biology are transforming drug therapy, the most cost-effective component of healthcare. Yet, at this time of scientific opportunity, shortages in specialized workforces limit the discovery and development of drugs and their safe use in adults and children. To fill that gap, Thomas Jefferson University and the Children’s Hospital of Philadelphia have developed a successful joint Clinical Pharmacology Fellowship Program to train clinician scientists that translate new discoveries into drugs that revolutionize care of adults and children.

PI_NAMEs: KRAFT, WALTER K (contact);WALDMAN, SCOTT A

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: Clinical Pharmacology;Training Programs

PROJECT_TITLE: Clinical Pharmacology Training Program


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative Type 2 diabetes has reached epidemic proportions world-wide and carries with it a high burden of cardiovascular morbidity and mortality. This application seeks to identify modifiable factors, namely hydrogen sulfide and its derivative methylated hydrogen sulfide, associated with risks of incident diabetes and diabetes-associated cardiovascular disease.

PI_NAMEs: LEMAITRE, ROZENN ;TOTAH, RHEEM ANGELA (contact)

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Affect;Age;Anabolism;Apoptosis;Atherosclerosis;Beta Cell;Bioinformatics;Blood;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;cardiovascular health;Cardiovascular system;Cell Line;Cell Physiology;Cells;Clinical;Clinical Trials;cohort;Cohort Studies;Cross-Sectional Studies;Cytoprotection;Data;Development;Diabetes Mellitus;Diabetes prevention;diabetes risk;Disease;endothelial dysfunction;enzyme biosynthesis;Epidemic;Event;Experimental Animal Model;experimental study;Family Study;Fasting;Functional disorder;Future;Glucose;glucose uptake;Heart;Heart failure;heart function;Heart Hypertrophy;Heart Injuries;Hepatic;HepG2;Human;Hydrogen Sulfide;improved;Incidence;Inhibition of Apoptosis;innovation;insight;Insulin;Insulin Resistance;insulin secretion;Ischemic Stroke;Islets of Langerhans;Japanese;Link;Liver;Longitudinal Studies;macrovascular disease;Mass Spectrum Analysis;Measures;Mediating;Metabolic;Metabolic Marker;Methylation;Modeling;Molecular;Morbidity - disease rate;mortality;Mus;Muscle Fibers;Myocardial Infarction;myocardial injury;Non-Insulin-Dependent Diabetes Mellitus;novel;Observational Study;Organ;Oxidative Stress;Palmitic Acids;Pancreas;Participant;Pathway interactions;Patients;Persons;Plasma;Play;population based;preclinical study;prevent;Proliferating;prospective;Prospective cohort;Prospective Studies;protective pathway;Public Health;Reactive Oxygen Species;response;Risk;Risk Factors;Rodent Model;Role;Sampling;secondary analysis;Signal Transduction;Small Interfering RNA;Testing;Toxic effect;transcriptomics;Vasodilator Agents;Ventricular

PROJECT_TITLE: Circulating hydrogen sulfide, diabetes and diabetes-related cardiovascular disease

STUDY_SECTION: CHSB

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


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Chronic Obstructive Pulmonary Disease;Data Science;Lung;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine

ORG_CITY: GAINESVILLE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE New data collection methods have the potential to revolutionize medicine by generating multiple and informationally complementary data streams from patients. A current roadblock is the efficient analysis of such multi-modal datasets. We propose to use causal graphical models to represent the data and identify the direct associations between variables; and use those algorithms to address important medical questions related to Chronic Obstructive Pulmonary Disease (COPD).

PI_NAMEs: BENOS, PANAGIOTIS V (contact);SPIRTES, PETER

PROGRAM_OFFICER_NAME: SHENOY, SIDDHARTH KAUP

PROJECT_TERMS: Address;Affect;Algorithms;Area;Biological Markers;biomarker selection;Black Box;Cancer Patient;Cause of Death;Chronic lung disease;Chronic Obstructive Pulmonary Disease;Classification;Clinical;Clinical Data;clinical development;clinically relevant;cohort;Combined Modality Therapy;Complex;complex data;Computer software;Data;Data Analyses;Data Collection;Data Set;data streams;deep learning;Diagnostic Procedure;disability;Disease;Disease Progression;diverse data;Evaluation;Explosion;Face;flexibility;Genetic;Genomics;Grant;Graph;graph learning;Health Care Costs;high dimensionality;Hospitals;Image;Internet;Joints;Knowledge;Learning;Letters;Libraries;low dose computed tomography;Lung nodule;Machine Learning;machine learning method;Malignant neoplasm of lung;Malignant Neoplasms;Medical;Medicine;Methodology;Methods;microbiome;Modality;Modeling;modifiable risk;mortality;multimodal data;multimodality;novel;Outcome;Pathogenesis;Patients;personalized biomarkers;personalized medicine;Pneumonia;precision medicine;predictive modeling;Probability;Process;Production;programs;Property;Pythons;radiological imaging;random forest;Research;Research Personnel;Risk Factors;Sampling;screening;Series;success;System;Theoretical model;theories;Time;tool;training data;Validation;web portal;web server;X-Ray Computed Tomography

PROJECT_TITLE: Interpretable graphical models for large multi-modal COPD data (R01HL159805)

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]


ADMINISTERING_IC: AG

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Lung;Lung Cancer;Palliative Care;Patient Safety;Physical Rehabilitation;Prevention;Rehabilitation

ORG_CITY: Columbus

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE The National Academy of Medicine has called for the inclusion of older adults in cancer research; yet, knowledge gaps remain with respect to important patient-reported outcomes, such as functional status, resiliency, and treatment toxicity, in this population. The proposed research seeks to test the feasibility and preliminary effect of one of the first virtual health supportive care clinical trials using physical therapy and progressive muscle relaxation among older adults with advanced lung cancer.

PI_NAMEs: PRESLEY, CAROLYN  (contact)

PROGRAM_OFFICER_NAME: NELLISSERY, MAGGIE JACOB

PROJECT_TERMS: Academy;active method;Activities of Daily Living;Adherence;Adult;Age;Aging;aging population;anti-cancer research;Anxiety;arm;Award;behavior change;Behavior Therapy;behavioral clinical trial;cancer clinical trial;Cancer Control;cancer diagnosis;cancer therapy;career;career development;Chest;Chiroptera;Chronic Disease;Clinical;Clinical Trials;Common Terminology Criteria for Adverse Events;Data;design;Diagnosis;disability;Disability prevention;Disease;Dyspnea;Effectiveness;Elderly;Enrollment;Ensure;European Organization for Research and Treatment of Cancer;EuroQOL;Exhibits;Fatigue;Feasibility Studies;feasibility testing;forging;functional decline;functional improvement;functional independence;functional outcomes;functional status;Geriatrics;Goals;Health Services;Immunooncology;Immunotherapy;improved;instrumental activity of daily living;International;Intervention;Intervention Studies;Intervention Trial;Joints;Knowledge;Leadership;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Medicine;Mental Depression;Mentors;Mentorship;Methods;Modeling;modifiable risk;Multicenter Studies;Muscle relaxation phase;novel;older adult;Oncologist;Oncology;Outcome;Pain;Participant;patient engagement;Patient Outcomes Assessments;patient population;Patient-Focused Outcomes;Patients;Physical Performance;Physical therapy;Physicians;Population;preservation;prevent;primary outcome;promote resilience;Prospective, cohort study;psychological symptom;randomized trial;randomized, clinical trials;Recovery;recruit;Relaxation;Reporting;Research;Research Design;Research Personnel;resilience;resilience research;response;retention rate;Risk Factors;Role;role model;Science;Scientist;secondary outcome;standard of care;study population;success;Supportive care;Symptom Burden;symptom treatment;Symptoms;Testing;Time;Training;Treatment Efficacy;Treatment-related toxicity;United States;virtual;virtual delivery;virtual health;Woman;Work

PROJECT_TITLE: Resiliency among Older Adults Receiving Lung Cancer Treatment: A Supportive Care Intervention Study


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

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Narrative Although stem/progenitor cells at the gastroesophageal junction have been shown in preclinical models to contribute to Barrett’s esophagus, their precise characteristics and mechanisms involved in neoplastic progression remain undefined. This proposed study will not only provide the molecular profile of mouse and human Barrett’s stem/progenitor cells but also offer insights into the role of p53 mutation and tuft cells in Barrett’s metaplasia and progression. The knowledge gained will provide a framework for identifying new therapy for reducing the risk of Barrett’s progression towards malignancy.

PI_NAMEs: QUE, JIANWEN ;WANG, TIMOTHY CRAGIN (contact)

PROGRAM_OFFICER_NAME: YASSIN, RIHAB R

PROJECT_TERMS: 3-Dimensional;Acceleration;Address;Adenocarcinoma;Affect;Automobile Driving;Barrett Esophagus;Basal Cell;Bile Acids;Biology;cancer type;carcinogenesis;carcinogenicity;Cell Physiology;Cells;Cellular biology;Cessation of life;Characteristics;Chromatin;Chronic;Clonal Evolution;Country;cytokine;Data;Development;Disease;Disease Progression;Distal;DNA Damage;Dysplasia;Dysplasia in Barrett's Esophagus;effective therapy;epigenomics;Epithelial Attachment;Esophageal Adenocarcinoma;Esophagitis;Esophagogastric Junction;Esophagus;Evolution;feeding;Financial Hardship;Gastric Adenocarcinoma;Gastroesophageal reflux disease;Gene Expression Profile;Genetic;Genetic Determinism;Genomics;Health;Human;human stem cells;In Vitro;in vivo;Incidence;Inflammation;Inflammatory Response;Injury;innovation;insight;Intestines;Joints;Knowledge;Lesion;Lymphoid Cell;Malignant - descriptor;Malignant neoplasm of esophagus;Malignant Neoplasms;malignant stomach neoplasm;Metaplasia;Modeling;Molecular;molecular phenotype;Molecular Profiling;mouse genetics;mouse model;Mus;mutant;Mutation;novel;novel strategies;novel therapeutics;Obesity;Organoids;Pathogenesis;Pathway interactions;Patients;Population;Pre-Clinical Model;progenitor;Resistance;response;Risk Factors;Risk Reduction;Role;Side;Simple Columnar Epithelium;single cell ATAC-seq;single-cell RNA sequencing;Specific qualifier value;stem cell differentiation;stem cell population;stem cells;stem-like cell;Stomach;stomach cardia;Testing;Tissues;TP53 gene;transcriptome sequencing;Transitional Epithelium;tumor;tumor progression;Work

PROJECT_TITLE: Gastroesophageal junction stem cells as the origin of Barretts esophagus and cancer


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Overall Project Narrative Lung cancer is the biggest cancer killer of men and women in the USA today and the research proposed in this SPORE seeks to harness recent advances in the molecular understanding of lung cancer pathogenesis, together with advances in clinically available chemotherapy, targeted therapy, radiation therapy, and immunotherapy, to develop new lung cancer therapies. We propose to attack multiple newly identified key vulnerabilities that lung cancers acquire during their pathogenesis that are present in tumor but not normal cells including metabolic, immunologic, microenvironmental, and replication stress vulnerabilities, and are not targets for currently available therapies. In addition, we are identifying molecular biomarkers that identify which lung cancers would be best treated by each of the new therapies to provide “precision medicine” and, if successful, the research of this SPORE should change the face of lung cancer therapy to provide a substantial beneficial impact on the public health.

PI_NAMEs: HEYMACH, JOHN V.;MINNA, JOHN D. (contact)

PROGRAM_OFFICER_NAME: UJHAZY, PETER

PROJECT_TERMS: Advocate;aurora kinase;Biological Markers;Biological Models;Biotechnology;Cancer Center;Cancer Patient;cancer therapy;career;cell killing;Characteristics;checkpoint inhibition;chemotherapy;Classification;Classification Scheme;CLIA certified;Clinical;Clinical Data;Clinical Research;clinical translation;Clinical Trials;Collaborations;Collagen;Communities;Coupled;Data;data resource;Data Science;Data Set;Development;Diagnosis;DNA Sequence Alteration;Enrollment;experience;Extracellular Matrix;Face;Genes;Genetically Engineered Mouse;genome-wide;Goals;Human;human model;immune checkpoint blockade;Immune response;Immunologics;Immunooncology;Immunotherapy;individual patient;inhibitor;innovation;Laboratory Scientists;Malignant neoplasm of lung;Malignant Neoplasms;Medical center;men;Metabolic;Metabolism;metabolomics;Molecular;molecular marker;molecular pathology;mouse model;mRNA Expression;multidisciplinary;Mutate;Mutation;neoplastic cell;Non-Small-Cell Lung Carcinoma;novel strategies;novel therapeutic intervention;novel therapeutics;Oncogenes;Organ;Outcome;Pathogenesis;patient derived xenograft model;Patients;PD-1/PD-L1;personalized biomarkers;personalized medicine;Pharmaceutical Preparations;pharmacologic;pre-clinical;Pre-Clinical Model;precision medicine;Preclinical Testing;preclinical trial;Productivity;programs;Public Health;Publications;Radiation therapy;Recording of previous events;replication stress;Research;Research Personnel;response;Rest;Role;Sampling;Selection for Treatments;Series;Site;small cell lung carcinoma;Specimen;targeted treatment;telomere;Testing;Texas;Therapeutic;therapeutic target;tissue resource;tool;translational cancer research;Translational Research;translational scientist;Translations;tumor;Tumor Cell Line;Tumor Immunity;tumor metabolism;tumor microenvironment;tumorigenesis;Universities;University of Texas M D Anderson Cancer Center;Validation;Woman;Xenograft procedure

PROJECT_TITLE: Targeting Lung Cancer Vulnerabilities


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Infectious Diseases;Neurosciences;Rare Diseases;Skin Cancer

ORG_CITY: TUCSON

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Neuroendocrine tumors arise in many tissues and can be particularly aggressive and metastatic, but it remains a challenge to treat them. Merkel cell carcinoma is a neuroendocrine skin cancer that can be caused by viral infection, which provides a unique opportunity to observe the steps leading to neuroendocrine tumor formation. We will analyze dynamic protein and genomic measurements to understand how normal cells can acquire neuroendocrine and metastatic features, because reversing this process could lead to new cancer therapies.

PI_NAMEs: PADI, MEGHA  (contact)

PROGRAM_OFFICER_NAME: READ-CONNOLE, ELIZABETH LEE

PROJECT_TERMS: Actins;Affect;Arizona;ATAC-seq;Automobile Driving;BETA2 protein;Biological Assay;Biological Models;Biometry;cancer therapy;carcinogenesis;Carcinogenesis Mechanism;Catalytic Domain;Cell Cycle;Cell Line;Cell model;cell motility;Cell Reprogramming;cell type;Cells;chromatin remodeling;Collaborations;Complement;Dana-Farber Cancer Institute;Data;Data Analyses;Data Set;Effector Cell;Endocrine;Epithelium;Etiology;Event;Exhibits;Gene Expression;Gene Expression Profile;Genes;Genetic Transcription;genome-wide;Genomics;Goals;Heterogeneity;Human;Image;In Vitro;Infection;Invaded;knock-down;Large T Antigen;Lead;Lung;Malignant Neoplasms;Measurement;Measures;Merkel cell carcinoma;Merkel Cells;Mesenchymal;Microtubules;migration;Molecular;Motility;Mus;Mutation;MYCL1 gene;Neoplasm Metastasis;network models;neural;neuroendocrine cancer;Neuroendocrine Tumors;neurogenesis;Neurosecretory Systems;Normal Cell;novel therapeutics;Oncogenes;Pancreas;Pathway interactions;Patients;Phenotype;Play;Polyomavirus;Process;Productivity;programs;Proliferating;Prostate;Protein Dynamics;Protein phosphatase;response;RNA analysis;Role;Series;Signal Pathway;Signal Transduction;Skin;Skin Cancer;Small T Antigen;System;targeted treatment;Testing;Therapeutic;Time;Tissues;transcription factor;transcriptome sequencing;Transforming Growth Factor beta;tumor;Tumor stage;Universities;Viral;Virus Diseases;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Unraveling the regulatory circuits that drive Merkel cell carcinoma

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


NIH_SPENDING_CATS: Cancer;Data Science;Lung;Lung Cancer

PHR: Administrative Core (Core A) Project Narrative The Lung Cancer SPORE Administrative Core provides scientific and administrative oversight for all of the SPORE Projects and Cores and the Developmental Research and Career Enhancement Programs. It also provides the main interface with patient advocates, NCI program staff, external and internal advisory boards, other Lung Cancer SPOREs, and other collaborating institutions.

PI_NAMEs: MINNA, JOHN D. (contact)

PROJECT_TERMS: Adherence;Advertising;Advocate;Bioinformatics;Biometry;Biotechnology;Budgets;Cancer Patient;career;clinical translation;Clinical Trials;Collaborations;Communication;Consult;data quality;Data Science;Data Science Core;data sharing;Development;Disputes;Ensure;Expenditure;Extramural Activities;Grant;Grant Review Process;industry partner;innovation;Institution;Interdisciplinary Study;Malignant neoplasm of lung;meetings;Mentors;Minority;minority patient;minority subjects;Monitor;Office of Administrative Management;Patients;Pharmacologic Substance;Policies;Process;programs;Progress Reports;Qualifying;quality assurance;Quality Control;recruit;Reporting;Research;Research Personnel;Research Project Grants;Resolution;Resource Sharing;Resources;Science;Texas;translational potential;Universities;University of Texas M D Anderson Cancer Center;Validation;videoconference;Woman;women patients;women subjects;Work

PROJECT_TITLE: Administrative Core A


PHR: Pathology Core (Core B) Project Narrative The Molecular Pathology and Tissue Resources Core will provide routine and innovative tissue resources and materials essential for achieving the aims of the SPORE projects, Developmental and Career Enhancement Programs, using IRB approved protocols, informed consent, and protection of patient confidentiality. This Core will play a crucial role on promoting collaboration among our own SPORE investigators and investigators at other Lung Cancer SPORE sites, and other intra and extra-mural collaborations, by coordinating the proper procurement, storage, and use of tissues, providing access to specimens and cell lines, and performing molecular and immuno-pathology methodologies. An important feature of the materials collected and analyzed by this Core is their clinical, histopathologic, immunohistochemical, immune microenvironment, and molecular annotation which provides clinical translation and synergism between available data and other studies performed on these samples.

PI_NAMEs: WISTUBA, IGNACIO I. (contact)

PROJECT_TERMS: B-Lymphocytes;Basic Science;Belief;biobank;Blood Banks;Blood Cells;Blood specimen;Cancer cell line;Cancer Patient;career;Catalogs;cell bank;Cell Line;Cells;Clinical;Clinical Data;Clinical Research;clinical translation;Clinical Trials;Collaborations;Collection;Confidentiality of Patient Information;Consent;Data;Data Science Core;data sharing;Deposition;Development;DNA;Drug or chemical Tissue Distribution;Ensure;Epithelial Cells;Extramural Activities;Fostering;Funding;Genomics;Goals;Grant;Guidelines;high standard;Histologic;Human;Immune;immune checkpoint blockade;Immunogenomics;immunopathology;Immunotherapy;individual patient;Informed Consent;innovation;Institution;Institutional Review Boards;Investigation;liquid biopsy;Lung;lung cancer cell;Lung Neoplasms;Malignant - descriptor;Malignant neoplasm of lung;Measures;Methodology;Methods;Molecular;Molecular Analysis;molecular pathology;Neoadjuvant Study;Neoplasm Circulating Cells;Non-Malignant;Non-Small-Cell Lung Carcinoma;novel;Operative Surgical Procedures;Pathogenesis;Pathologic;Pathology;Patient-Focused Outcomes;Patients;Peer Review;personalized medicine;Play;Positioning Attribute;Process;programs;Proteins;Protocols documentation;Publications;Reagent;Research;Research Activity;Research Personnel;Research Project Grants;Resectable;Resource Sharing;Resources;RNA;Role;Sampling;Selection for Treatments;Services;Site;small cell lung carcinoma;Specimen;success;synergism;Testing;Tissue Banks;Tissue Microarray;Tissue Procurements;tissue resource;Tissue Sample;Tissues;translational applications;translational cancer research;Translational Research;tumor;Tumor Cell Line;tumor xenograft;tumor-immune system interactions;United States National Institutes of Health;University of Texas M D Anderson Cancer Center;Xenograft procedure

PROJECT_TITLE: Molecular Pathology and Tissue Resource


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: PALO ALTO

ORG_NAME: VETERANS ADMIN PALO ALTO HEALTH CARE SYS

ORG_STATE: CA

PHR: This is an opportunity to critically examine access to emergency care within the VA and foster organizational improvement of the emergency care system. Emergency care access is particularly problematic for Veterans, in part because VA emergency departments (ED) are far and few between, and Veterans are often uncertain where to go when confronted with an emergency. This is particularly true for Veterans with special access issues, like those living in rural areas, those lacking housing, and women. We will assess capabilities and resources of VA EDs to care for acutely ill Veterans. Further, by analyzing ED data and speaking with Veterans, we will better understand where and why Veterans access the emergency care system (in both VA and non-VA settings) and will identify barriers in access amendable in future intervention and policy changes. Ultimately, our results are highly actionable to our operational partners and can be directly used to improve access to emergency care for Veterans during times of crisis.

PI_NAMEs: VASHI, ANITA A (contact)

PROJECT_TERMS: Accident and Emergency department;Accountability;accountable care organization;Accounting;acute care;Address;Advocate;Ambulatory Care Facilities;Area;Bypass;California;care seeking;care systems;Caring;Chest Pain;Chronic;cohort;Communities;Community Healthcare;Complex;Confusion;contextual factors;cost;Country;Data;Decision Making;design;Eligibility Determination;Emergency Care;Emergency department visit;Emergency Medicine;Emergency Situation;Enrollment;Ensure;Equipment and supply inventories;Equity;experience;Failure;Family;Fostering;Funding;Future;Gender;Government;Gunshot wound;Health;health care availability;health care service;Health Services Accessibility;Health system;Healthcare;Healthcare Systems;Home;Housing;Improve Access;improved;Infrastructure;innovation;Institute of Medicine (U.S.);Insurance;Intervention;Interview;Knowledge;Medical emergency;Medicare;Methods;military veteran;Myocardial Infarction;Outcome;Patients;Phase;Policies;preference;prevent;Primary Care;Provider;Qualitative Methods;Quality of Care;Reporting;Research;Resources;rural area;rurality;safety net;service organization;Services;Structure;Surveys;System;Translating;United States;Variant;Veterans;Visit;Wife;Woman;Work

PROJECT_TITLE: Veteran Access to Emergency Care

STUDY_SECTION_NAME: HSR-5 Health Care System Organization and Delivery and Women's Health[HSR5]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Data Science;Genetics;Human Genome;Lung;Lung Cancer;Networking and Information Technology R&D (NITRD)

PHR: Data Sciences Core (Core C) Project Narrative The Data Science Core ensures that all experiments performed by the core are properly designed, and that the data collected by those experiments are stored safely, analyzed sensibly, and made available to other SPORE investigators (and ultimately to other lung cancer researchers) in order to further the ultimate goal of translating knowledge from the research lab into the clinic. The Data Sciences Core interfaces with all of the SPORE Projects, Developmental Research (DRP), and Career Enhancement Programs (CEP), and works to integrate the findings from the Molecular Pathology Core using appropriate biostatistical and computational biology approaches into the SPORE Projects. The Data Sciences Core provides documents such as Sweave for publication to allow others to reproduce complex analyses, and works to develop and maintain a database for the large-scale datasets of the SPORE including dataset deposits as required by the NIH/NCI (e.g. dbGAP and others), to provide datasets available to extra mural sources to facilitate horizontal and vertical collaborations by the SPORE.

PI_NAMEs: XIE, YANG  (contact)

PROJECT_TERMS: Archives;Biochemical;Bioinformatics;bioinformatics infrastructure;Biological;Biometry;Cancer Center;career;career development;Caring;Cell Line;Clinic;Clinical;Clinical Data;clinical translation;Clinical Trials;Collaborations;Communities;Complex;Complex Analysis;Computational Biology;Computer Analysis;Data;Data Analyses;Data Analytics;data exchange;data integration;data integrity;data management;Data Science;Data Science Core;Data Set;data sharing;Data Storage and Retrieval;database of Genotypes and Phenotypes;Databases;Deposition;design;Development;Doctor of Medicine;Ensure;experience;experimental study;Extramural Activities;Faculty;flexibility;Freezing;Funding;genome-wide;Genomic Data Commons;Genomics;Goals;Histologic;Human;Human Resources;Image;Immune;Immune response;Informatics;innovation;Institution;Knowledge;Laboratories;Laboratory Research;large scale data;large-scale database;Link;Literature;Location;Lung;Malignant neoplasm of lung;Medical center;meetings;member;metabolomics;Methods;Modernization;Molecular;molecular pathology;mouse model;multiple data types;Mutation;neoplastic cell;Normal Cell;Pathology;Patients;Pharmaceutical Preparations;Phase;Phenotype;programs;Proteomics;public database;Publications;Research;Research Personnel;Resources;Retrieval;Sampling;Secure;Services;simulation;Site;Source;Statistical Data Interpretation;Statistical Models;success;symposium;System;Texas;Tissue Banks;Translating;translational cancer research;translational research program;tumor;Tumor Cell Line;tumor xenograft;United States National Institutes of Health;Universities;videoconference;web site;web-accessible;Work;Xenograft Model

PROJECT_TITLE: Data Science Core (Data Analytics, Biostatistics and Database)


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

PHR: Project 1 Project Narrative The goal of SPORE Project #1 “Targeting Metabolic Vulnerabilities in Lung Cancer” is to identify previously unknown acquired vulnerabilities related to tumor cell metabolism in lung cancer and in preclinical models test the effect of targeting these vulnerabilities alone and with clinically available therapies. This proposal will identify specific metabolic activities that predict disease progression in humans and will thoroughly study the effect of therapeutically inhibiting one such activity, lactate transport, on tumor growth and metastasis in preclinical models in mice. In addition, this project will provide some of the first data on how lung cancer metabolism affects its tumor microenvironment (and vice versa) particularly related to anti-tumor immune responses which will be of value to all of the other SPORE Projects.

PI_NAMEs: DEBERARDINIS, RALPH J (contact)

PROJECT_TERMS: Accounting;Address;Affect;anti-tumor immune response;Area;biological heterogeneity;cancer cell;Cancer Patient;Carrier Proteins;CD147 antigen;Cell Communication;cell type;Cells;Cellular Metabolic Process;Clinical;Clinical Data;Clinical Research;Clinical Trials;clinically relevant;cohort;CRISPR/Cas technology;Data;Data Set;Dependence;design;Disease Progression;Dissection;exome sequencing;follow-up;Genetic;Glucose;Goals;Growth;Heterogeneity;Histologic;Histopathology;Human;human subject;Image;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;Immunotherapy;Impairment;in vivo;Infusion procedures;inhibitor;innovation;interest;Intrinsic factor;Label;Lung;Lung Adenocarcinoma;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;Maps;Mediating;Metabolic;Metabolic Pathway;metabolic phenotype;Metabolism;metabolomics;Methods;Modeling;Molecular;Molecular Profiling;mouse model;multidisciplinary;multiparametric imaging;Mus;Needle biopsy procedure;Neoplasm Metastasis;new therapeutic target;Non-Small-Cell Lung Carcinoma;novel;Nutrient;Oncogenic;Outcome;patient derived xenograft model;Patients;Pattern;pharmacologic;Phenotype;Population;Positioning Attribute;pre-clinical;Pre-Clinical Model;predict clinical outcome;predictive marker;Predisposition;Progression-Free Survivals;Proteins;Recording of previous events;Reporting;somatic cell gene editing;Source;Squamous Cell Lung Carcinoma;Structure of parenchyma of lung;System;T-Lymphocyte;Testing;Therapeutic;Therapeutic Effect;Therapeutic Intervention;therapeutic target;Time;Tissues;transcriptome sequencing;Translating;treatment response;tumor;tumor growth;tumor heterogeneity;tumor metabolism;tumor microenvironment;tumor progression;tumor xenograft;tumor-immune system interactions;uptake;Work

PROJECT_TITLE: Project 1: Targeting Metabolic Vulnerabilities in Lung Cancer


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Lung;Lung Cancer

PHR: Project 2 Project Narrative Although PD-1/PD-L1 immune checkpoint blockade (PCB) therapy has transformed the treatment of non-small cell lung cancer (NSCLC) patients, the majority still do not have an objective response to PCB and the molecular determinants of therapeutic resistance are not well understood. We have found that STK11/LKB1 mutant NSCLC is one the largest genomic subgroups associated with a “cold” immune phenotype, accounting for ~40% of the primary resistance to checkpoint blockade therapy, and we hypothesize that there are distinct biological features of these tumors that may contribute their immunologically inert phenotype and that represent therapeutic vulnerabilities. In this proposal will leverage unique preclinical and clinical resources to comprehensively investigate the immune landscape of STK11/LKB1 mutant lung adenocarcinoma and test whether targeting two potential therapeutic vulnerabilities- lactate metabolism and replication stress- can enhance antitumor immunity in these tumors.

PI_NAMEs: HEYMACH, JOHN V. (contact)

PROJECT_TERMS: Accounting;Biological;Cancer Patient;CD8B1 gene;Cells;chemotherapy;Clinic;Clinical;cohort;Collaborations;Combination Drug Therapy;Dependence;Disease;DNA Sequence Alteration;driver mutation;effector T cell;Epidermal Growth Factor Receptor;Equilibrium;gemcitabine;Genetic;Genomics;Glutaminase;Glutamine;Goals;Human;Immune;immune checkpoint blockade;Immune Targeting;Immunogenomics;Immunologics;immunosuppressed;Immunosuppression;Immunotherapy;improved;inhibitor;knock-down;KRAS2 gene;Label;Laboratories;Lung Adenocarcinoma;Macrophage;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Metabolic;metabolic phenotype;Metabolism;Molecular;mouse model;mutant;Mutation;neoplastic cell;Non-Small-Cell Lung Carcinoma;novel therapeutic intervention;nucleoside analog;Nucleotides;Pathway interactions;patient population;Patients;PD-1/PD-L1;pharmacologic;Phenotype;Population;pre-clinical;Pre-Clinical Model;Production;programmed cell death ligand 1;Proteins;Publications;replication stress;Reporting;Resected;Resistance;Resources;response;single-cell RNA sequencing;Specimen;STK11 gene;Stress;Subgroup;Systemic Therapy;T-Lymphocyte Subsets;targeted agent;Testing;Therapeutic;Therapeutic Agents;therapeutically effective;therapy resistant;Translating;tumor;tumor growth;Tumor Immunity;Tumor Suppressor Proteins;tumor-immune system interactions;Tumor-infiltrating immune cells;Validation

PROJECT_TITLE: Project 2: Targeting Immune Vulnerabilities in Lung Cancer


NIH_SPENDING_CATS: Cancer;Immunotherapy;Lung;Lung Cancer

PHR: PROJECT 3 PROJECT NARRATIVE Substantial therapeutic advances have been made in the treatment of NSCLC based upon the incorporation of immune checkpoint inhibitors of the PD-1/PD-L1 axis, but durable responses are observed in only 15-20% of patients. Based upon our preliminary data, we hypothesize that extracellular matrix deposition and collagen crosslinking in the tumor microenvironment suppress tumor-infiltrating immune cells, facilitating tumor invasion and metastasis and resistance to immune checkpoint blockade inhibitors. Using parallel study of pre-clinical models and assessment of patient samples, we will address this hypothesis and explore clinical translational opportunities by: i) evaluating the role of collagen crosslinking enzymes and a fibrotic extracellular matrix on the immune cell profile of murine and human lung tumors, ii) determine how treatment with immune checkpoint inhibitors (ICI, e.g. anti-PD-(L)1 and/or anti-CTLA-4) alters ECM composition and crosslinking in murine and patient tumors, and iii) test the efficacy of agents that block fibrotic collagen crosslinking with or without immune checkpoint inhibitors to reverse the suppression of a productive intra-tumoral immune response in preclinical models.

PI_NAMEs: GIBBONS, DON LYNN (contact)

PROJECT_TERMS: Adjuvant Study;Affect;Aftercare;anti-CTLA4;anti-PD-1;anti-PD-L1;Benchmarking;Bioinformatics;Biometry;Blood specimen;Cancer Model;CD8-Positive T-Lymphocytes;Cells;checkpoint therapy;chemotherapy;Clinical;Clinical Oncology;clinical translation;Collagen;comparative;comparative efficacy;crosslink;CTLA4 gene;Data;Data Analyses;Deposition;drug development;efficacy testing;Enzymes;Extracellular Matrix;Genetic;Genetically Engineered Mouse;Human;human model;Hylobates Genus;Immune;immune activation;immune cell infiltrate;immune checkpoint blockade;Immune checkpoint inhibitor;Immune response;Immunogenomics;Immunologic Factors;Immunologic Surveillance;Immunotherapy;inhibitor;kinase inhibitor;Knowledge;LHX2 gene;LOX gene;Lung Neoplasms;Malignant neoplasm of lung;Mediating;member;Modeling;Molecular;molecular pathology;mouse model;multidisciplinary;Mus;Neoadjuvant Study;Neoadjuvant Therapy;Neoplasm Metastasis;nintedanib;Non-Small-Cell Lung Carcinoma;Operative Surgical Procedures;Patients;PD-1/PD-L1;pharmacologic;pre-clinical;pre-clinical assessment;Pre-Clinical Model;preclinical study;Primary Neoplasm;Productivity;programmed cell death protein 1;Protein-Lysine 6-Oxidase;PTPN6 gene;Research Personnel;Resectable;Resistance;resistance mechanism;response;Role;Sampling;Signal Transduction;Specimen;T-cell receptor repertoire;T-Lymphocyte;targeted agent;Testing;Therapeutic;therapy resistant;Tissue Microarray;Translating;translational potential;treatment response;tumor;Tumor Cell Invasion;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;tumor-immune system interactions;Tumor-infiltrating immune cells;University of Texas M D Anderson Cancer Center

PROJECT_TITLE: Project 3: Targeting Vulnerabilities in the Fibrotic Extracellular Matrix (ECM) of Lung Cancers


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Genetics;Immunotherapy;Lung;Lung Cancer;Orphan Drug;Precision Medicine;Rare Diseases

PHR: Project 4 Project Narrative Progress is slow in treating advanced small cell lung cancers (SCLC), and there remains an urgent need to provide patients with long-term durable responses. Approaches to develop SCLC targeted therapy, improve responses to immunotherapy, and to more effectively treat primary chemotherapy relapsed and refractory SCLC are acutely needed. Our Project addresses all of these aspects by testing targeted therapy induced replication stress (RS) as a potential SCLC therapeutic vulnerability which also would increase innate immune responses against SCLC, and lead to improved responses against immune checkpoint blockade immunotherapy. This new SCLC RS vulnerability is studied through a series of preclinical translational experiments and an investigator- initiated Phase 2 clinical trial.

PI_NAMEs: BYERS, LAUREN AVERETT (contact)

PROJECT_TERMS: Acute;Address;Animal Model;anti-cancer research;anti-PD-1;anti-PD-L1;Antitumor Response;aurora kinase;aurora kinase A;Bioinformatics;biological adaptation to stress;Biology;biomarker driven;biomarker identification;Blood;Blood specimen;Cancer Biology;cancer cell;Cancer cell line;Cancer Model;Cancer Patient;cancer therapy;candidate marker;CD34 gene;Cell Death;Cells;chemotherapy;Chromosome abnormality;Clinical;clinical development;Clinical Trials;Cytoplasm;cytotoxicity;Data;Data Science Core;DNA;DNA biosynthesis;DNA Damage;DNA Repair;DNA Repair Inhibition;DNA replication fork;effective therapy;efficacy evaluation;experience;experimental study;Extensive Stage;Gene Activation;Genetic;genetic approach;Genetically Engineered Mouse;Genomic Instability;Goals;Human;Immune;immune checkpoint;immune checkpoint blockade;Immune checkpoint inhibitor;Immune system;Immunocompetent;Immunotherapy;Impairment;improved;In Vitro;in vivo;inhibitor;Innate Immune Response;Innate Immune System;kinase inhibitor;Laboratories;Lead;lung cancer cell;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Mitotic;Modeling;Molecular;Molecular Profiling;mouse model;Mus;mutant;Mutation;MYC-Family Oncogene;Natural Immunity;Neoplasm Circulating Cells;neoplastic cell;Non-Small-Cell Lung Carcinoma;novel;Oncogene Activation;Oncogenes;Oncogenic;overexpression;Pathology;Pathway interactions;patient derived xenograft model;Patients;pembrolizumab;personalized medicine;Pharmaceutical Preparations;pharmacologic;Phase II Clinical Trials;Phenotype;Poly(ADP-ribose) Polymerase Inhibitor;pre-clinical;Pre-Clinical Model;preclinical study;predicting response;predictive marker;Productivity;programmed cell death ligand 1;protein expression;RB1 gene;RBL2 gene;reconstitution;Refractory;Relapse;replication stress;Research Personnel;Resistance;response;safety assessment;Series;small cell lung carcinoma;Specimen;Stimulator of Interferon Genes;targeted agent;targeted cancer therapy;targeted treatment;Telomerase;telomere;Testing;Therapeutic;therapeutic target;Thioguanine;TP53 gene;tumor;tumor-immune system interactions;tumorigenesis;Umbilical cord structure;Xenograft procedure

PROJECT_TITLE: Project 4: Therapeutic Targeting of Replication Stress Vulnerabilities in Small Cell Lung Cancer


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: Public Health Relevance/Narrative Fluorescence microscopy is an increasingly critical tool in biomedical research. The proposed research seeks to advance public health by allowing direct visualization at the nanoscale of subcellular mechanisms and fostering new insights into a range of biological processes. Reflecting NIH’s core mission, these efforts will support the development of fundamental knowledge that enhances human health.

PI_NAMEs: HUANG, FANG  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: 3-Dimensional;Actins;analytical method;Biological Process;biological research;Biomedical Research;Budgets;cell fixing;Cell Lineage;Cell Physiology;Cells;cellular imaging;Cellular Structures;Chromatin;constriction;Deterioration;Development;diffraction of light;Dyes;Dynein ATPase;Epigenetic Process;Event;Fission Yeast;Fluorescence;Fluorescence Microscopy;Fostering;Gene Expression Profile;Goals;Growth Cones;Health;Human;Image;imaging system;Imaging technology;improved;innovation;insight;instrument;Knowledge;Label;macromolecular assembly;Maps;Methods;Microfilaments;Microscopy;Microtubules;Mission;Modernization;Molecular;molecular imaging;Molecular Motors;Myosin ATPase;nanoscale;neuronal growth;novel;optical imaging;Phase;Photons;Positioning Attribute;Proteins;Public Health;public health relevance;reconstruction;Research;Resolution;Sampling;single molecule;Specificity;Specimen;structural imaging;Structural Models;Structure;superresolution imaging;superresolution microscopy;Surface;Thinness;Three-Dimensional Imaging;Time;Tissues;tool;ultra high resolution;United States National Institutes of Health;Visualization

PROJECT_TITLE: Ultra-high resolution structural and molecular imaging of cells and tissues

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


NIH_SPENDING_CATS: Cancer;Lung;Lung Cancer

PHR: Developmental Research Program (DRP) Project Narrative Project Narrative The Lung Cancer SPORE Developmental Research Program (DRP) provides pilot project funding for lung cancer projects, prepared by early career or established faculty investigators with the potential for clinical translation with significant impact on the diagnosis, prevention, or treatment of lung cancer. With this funding comes access to SPORE Core Pathology and Data Sciences Resources and mentorship by experienced lung cancer investigators and patient advocates. These pilot Developmental Research Program projects should lead to publications, applications for other grant funding, and as appropriate, clinical trial development, and advancement as part of the overall SPORE Program.

PROJECT_TERMS: Advocate;anti-cancer research;Applications Grants;Area;Award;Budgets;Cancer Biology;Cancer Patient;Cancer Research Project;career;Clinic;Clinical;clinical translation;Clinical Trials;Communication;Critiques;Data;Data Analyses;Data Science;data science resource;Development;Diagnosis;Direct Costs;Discipline;Doctor of Philosophy;Environment;experience;Extramural Activities;Faculty;Fostering;Funding;Funding Mechanisms;Generations;Goals;Grant;Guidelines;Human Resources;innovation;Institution;interest;Knowledge;Laboratories;Malignant neoplasm of lung;Manuscripts;meetings;member;Mentors;Mentorship;Minority;Molecular;molecular pathology;novel strategies;Pathogenesis;Pathology;Patients;Peer Review;Pilot Projects;Pre-Clinical Model;Preparation;Prevention;Prognosis;Program Research Project Grants;programs;Publications;Qualifying;Recording of previous events;recruit;Research;research and development;Research Personnel;Research Project Grants;Resources;Role;Running;Scientific Advances and Accomplishments;Scientist;Structure;Technology;Texas;Training;Translating;translational cancer research;Translational Research;Universities;University of Texas M D Anderson Cancer Center;Woman;Work

PROJECT_TITLE: DRP Core: Developmental Research Program


PHR: Career Enhancement Program (CEP) Project Narrative The Lung Cancer SPORE Career Enhancement Program (CEP) provides pilot project funding for lung cancer projects, prepared by early career faculty investigators with the potential for clinical translation with significant impact on the diagnosis, prevention, or treatment of lung cancer. With this funding comes access to SPORE Core Pathology and Data Sciences Resources and mentorship by experienced lung cancer investigators and patient advocates. These pilot projects should lead to publications, applications for other grant funding and, as appropriate, clinical trial development, and advancement as part of the overall SPORE Program..

PROJECT_TERMS: Advocate;anti-cancer research;Award;Budgets;Cancer Biology;career;career development;Career Mobility;Clinical;clinical application;clinical translation;Clinical Trials;Data;Data Science;data science resource;detection method;Development;Diagnosis;Direct Costs;Disease;Doctor of Philosophy;early-career faculty;Environment;Evaluation;experience;Faculty;Fostering;Funding;Generations;Goals;Grant;Guidelines;innovation;Institution;instructor;interest;Joints;Malignant neoplasm of lung;Malignant Neoplasms;Mentors;Mentorship;mid-career faculty;Minority;molecular pathology;next generation;novel strategies;Oncologist;Pathogenesis;Pathology;Patients;Peer Review;Physicians;Pilot Projects;Play;Postdoctoral Fellow;Pre-Clinical Model;Prevention;Prognosis;programs;Publications;Qualifying;Recording of previous events;recruit;Research;Research Personnel;Research Project Grants;Resolution;Resources;Role;Running;Scientist;Site;Talents;Technology;Texas;Training;Translating;translational cancer research;Universities;University of Texas M D Anderson Cancer Center;Woman

PROJECT_TITLE: CEP Core: Career Enhancement Program


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurodegenerative;Neurosciences;Parkinson's Disease

ORG_DEPT: NEUROSURGERY

PHR: Project narrative How people select actions, cancel unwanted or inappropriate actions and switch actions in response to new incoming information is a fundamental neurobiological question that is of high impact for understanding how the human brain functions. Many neurological and psychiatric disorders, such as Parkinson’s disease (PD) and obsessive compulsive disorder (OCD), point to impaired brain circuitry responsible for these three suppression functions. The proposed study will develop a neurocomputational model to better understand these mechanisms and evaluate these models with direct recordings from patient volunteers during neurosurgical procedures.

PI_NAMEs: CHRISTOPOULOS, VASILEIOS N;POURATIAN, NADER  (contact)

PROGRAM_OFFICER_NAME: GEBREHIWET, HERMON RUSSOM

PROJECT_TERMS: Affect;aged;Architecture;Basal Ganglia;Behavior;Behavioral;Brain;brain circuitry;brain dysfunction;Clinical;Collaborations;Computer Models;cost;Data;Deep Brain Stimulation;design;Disease;Disparate;Effectiveness;Environment;environmental change;experimental study;Face;Failure;flexibility;Funding;Gilles de la Tourette syndrome;Goals;high reward;Human;Hybrids;implantation;improved;Individual;Joystick;kinematics;Manufactured basketball;Maps;Mediating;Mental disorders;Modeling;Motor;motor behavior;Movement;Nervous System Disorder;neural;neural circuit;Neurobiology;neuromechanism;neurophysiology;neuropsychiatric disorder;neuroregulation;neurorestoration;Neurosciences;Neurosurgical Procedures;Obsessive-Compulsive Disorder;Operative Surgical Procedures;Outcome;Parkinson Disease;Participant;Pathway interactions;Patients;Persons;Physiological;Physiology;predictive modeling;Regulation;Research Personnel;Resolution;response;Rewards;Role;sensorimotor system;Signal Transduction;Source;Specificity;STN stimulation;Structure of subthalamic nucleus;Testing;theories;Update;Validation;volunteer;Work

PROJECT_TITLE: Modeling and Mapping Human Action Regulation Networks


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Mental Illness;Post-Traumatic Stress Disorder (PTSD);Primary Health Care;Social Determinants of Health

ORG_CITY: ANN ARBOR

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative The proposed project is relevant to public health because it will develop a stepped-care intervention for PTSD that can be readily applied in real-world practice and community settings, thus helping to expand access to efficacious treatment among underserved individuals. This innovative approach will improve the scalability and efficiency of PTSD treatment by reducing costs while maximizing effectiveness. It is relevant to the NIMH’s mission to test bundled, validated intervention components that have the greatest impact on patients’ functioning.

PI_NAMEs: SRIPADA, REBECCA KAUFMAN (contact)

PROGRAM_OFFICER_NAME: HAIM, ADAM J

PROJECT_TERMS: adaptive intervention;Address;Adherence;Administrator;Adult;Affect;Age;Behavior Therapy;burden of illness;Caring;Child;Clinical;clinical practice;clinically significant;Cognition;Cognitive Therapy;community setting;coping mechanism;cost;Cost Effectiveness Analysis;Data;effective intervention;effective therapy;Effectiveness;effectiveness testing;efficacious treatment;Evidence based treatment;Experimental Designs;Federally Qualified Health Center;follow-up;Frequencies;future implementation;Goals;Health Services Accessibility;Improve Access;improved;Individual;innovation;Intervention;Interview;Left;Low Income Population;Mediating;Mediator;Mental disorders;Methodology;Mission;Mobile Health Application;Modeling;National Institute of Mental Health;novel;Participant;patient oriented;patient screening;Patients;Post-Traumatic Stress Disorders;practice setting;Primary Care;process evaluation;Provider;Public Health;Qualifying;Quality-Adjusted Life Years;Randomized;Randomized, Controlled Trials;reduce symptoms;Research;Resource-limited setting;Resources;response;Self Efficacy;Self Management;Sequential Multiple Assignment Randomized Trial;Severities;sex;Symptoms;telehealth;Testing;Therapeutic Effect;Titrations;Training;Trauma;Treatment outcome;treatment response;Treatment Step;treatment strategy;trial design;Underserved Population;Vulnerable Populations;Work

PROJECT_TITLE: Testing Adaptive Interventions to Improve PTSD Treatment Outcomes in Federally Qualified Health Centers


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Rare Diseases;Vector-Borne Diseases;Zika Virus

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE A deeper understanding of flavivirus infection mechanisms could help lessen the public health impact of these important human pathogens by aiding the development of antiviral therapies. This project seeks to elucidate how the flavivirus nonstructural 5 (NS5) protein impacts host innate immune responses by using innovative molecular virology approaches. These efforts will focus on studying these activities on a genetic level through deep mutagenesis screens.

PI_NAMEs: EVANS, MATTHEW J (contact);GARCIA-SASTRE, ADOLFO

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Amino Acids;Animal Model;Animals;antagonist;Anti-viral Response;Anti-viral Therapy;antiviral drug development;Attenuated;Attenuated Vaccines;Binding;Cell Communication;Cell Culture Techniques;combat;Complex;Conserved Sequence;CRISPR screen;Dengue Virus;design;Disease;Disease Outbreaks;Engineering;Evolution;Flavivirus;Flavivirus Infections;Future;future outbreak;Genes;Genetic;Genetic Determinism;Goals;Human;human pathogen;Immune;Immune response;Immunosuppression;In Vitro;in vivo;Infection;inhibitor;Innate Immune Response;innovation;insight;Integration Host Factors;interferon antagonist;Interferon Type I;Interferons;Knock-out;Libraries;Maps;Mediating;Methods;Modification;Molecular;Molecular Virology;Mus;Mutagenesis;mutant;Mutate;Mutation;mutation screening;Nonstructural Protein;novel;Orthologous Gene;Pathogenesis;Pattern;Predisposition;pressure;Process;programs;Property;Proteins;Proteomics;Public Health;recruit;Reporting;Resistance;Resolution;response;Signal Induction;Signal Transduction;Site;Small Interfering RNA;Stat2 protein;Structure;Surveys;targeted treatment;Testing;therapeutic target;therapy development;Time;tool;transcription factor;Tropism;Ubiquitin;ubiquitin ligase;Ubiquitination;Vaccine Design;Vaccines;Variant;vector-borne;Viral;Viral Genes;Virus;whole genome;Work;Yellow fever virus;Zika Virus

PROJECT_TITLE: Zika virus nonstructural protein 5 inhibition of interferon signaling

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


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

ORG_CITY: STANFORD

ORG_DEPT: PEDIATRICS

ORG_NAME: STANFORD UNIVERSITY

PHR: NARRATIVE We investigate the molecular and cellular mechanisms of small cell lung cancer (SCLC) development and response to therapy using a combination of mouse genetics, primary human tumors, and molecular, biochemical, and genomic approaches. A better understanding of intra-tumoral heterogeneity and of the driving factors in SCLC metastasis will instruct the development of novel therapeutic approaches to target the most lethal form of lung cancer.

PI_NAMEs: SAGE, JULIEN  (contact)

PROGRAM_OFFICER_NAME: MAAS, STEFAN

PROJECT_TERMS: Address;Automobile Driving;Biochemical;Biology;Brain;cancer cell;Cancer Model;Cancer Patient;Cell Line;Cells;clinical trial implementation;Development;early detection biomarkers;Evolution;Genetic;Genomic approach;Genomics;Growth;Health;Human;human model;in vivo;innovation;insight;interest;Laboratories;lung cancer cell;Maintenance;Malignant neoplasm of lung;Modeling;Molecular;mouse genetics;mouse model;Mus;mutant;Neoplasm Metastasis;neuroendocrine cancer;Neuronal Differentiation;Neurosecretory Systems;notch protein;novel;novel therapeutic intervention;Organ;patient derived xenograft model;Patients;Phenotype;Research;Research Personnel;response;retinoblastoma tumor suppressor;Role;Sampling;Signal Transduction;small cell lung carcinoma;Smoker;stem cell model;Stromal Cells;Testing;tool;treatment response;tumor;tumor heterogeneity;tumor progression;Tumor-Derived;tumorigenic;virtual;Work

PROJECT_TITLE: Investigating molecular and cellular mechanisms of SCLC development to identify novel therapeutic strategies


NIH_SPENDING_CATS: Childhood Injury;Clinical Research;Immunotherapy;Infectious Diseases;Pediatric;Physical Injury - Accidents and Adverse Effects;Prevention;Unintentional Childhood Injury;Wound Healing and Care

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

PHR: Project Narrative Burn injuries are a major public health issue, affecting two million people in the United States annually, in which the most common acute complications are infectious related. With this MIRA application I propose to elucidate the mechanisms underlying systemic lymphocyte dysfunction and to understand the spatial differentiation and function of monocyte to macrophage transition after burn injury to ultimately inform immunomodulatory therapies for prevention of infection following severe burn injury. The work proposed in this application will fill a gap in understanding the underlying mechanisms of immune dysfunction following critical injury/illness as well as provide an important building block for future clinical trials involving the use of immunomodulatory therapy to improve outcomes following thermal injury.

PI_NAMEs: THAKKAR, RAJAN  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Acute;Adolescent;Affect;age group;Apoptotic;Automobile Driving;Biological Assay;Biological Markers;Blood specimen;Burn injury;burn model;burn wound;Caring;Cell surface;Cessation of life;Childhood;Clinical Trials;Combined Modality Therapy;cytokine;design;FDA approved;Functional disorder;Future;Goals;heat injury;high risk;immune function;Immune response;Immune System Diseases;immunomodulatory therapies;improved;improved outcome;in vivo;Infection;Infection prevention;Inflammation;Inflammatory Response;Injury;insight;Lymphocyte;Macrophage;Modeling;monocyte;Morbidity - disease rate;mortality;mouse model;Mus;Operative Surgical Procedures;Outcome;Patient-Focused Outcomes;Persons;Phenotype;Plasma;Population;Predisposition;prevent;Proteins;Public Health;Research;response;Route;Sampling;Sepsis;severe burns;severe injury;Therapeutic;therapy development;Tissue Sample;Tissues;Trauma;United States;Work;wound bed;wound healing

PROJECT_TITLE: Elucidating the Mechanisms of Immune Dysfunction After Severe Burn Injury

STUDY_SECTION: MRAD

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


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Dissemination and Implementation Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Patient Safety;Precision Medicine;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Ensuring that the potential of genomics to improve health is equally available to all populations is a national priority in genomic medicine. Knowledge of how to promote health equity during the implementation of pharmacogenomics (PGx), an application of genomic medicine, is limited. This quantitative and qualitative project will address the need for empirical research in real-world settings on the impact of pharmacogenomics on minority populations and help to tailor risk communication strategies during PGx implementation to improve care for minority patients.

PI_NAMEs: SAULSBERRY, LOREN  (contact)

PROGRAM_OFFICER_NAME: KULCHAK RAHM, ALANNA LEE

PROJECT_TERMS: Active Learning;Adoption;Automobile Driving;Award;Belief;care delivery;career;career development;Caring;Characteristics;Chicago;Chronic Disease;Clinical;clinical implementation;clinical practice;Clinical Trials;Communication;comorbidity;Data Set;Decision Making;design;Development;Development Plans;dissemination science;Doctor of Philosophy;Drug Prescriptions;Drug usage;Educational workshop;Empirical Research;Ensure;ethnic disparity;ethnic diversity;Ethnic Origin;evidence base;expectation;experience;experimental study;Exposure to;Focus Groups;Foundations;Future;Genetic;genome sciences;Genomic medicine;Genomics;Goals;Grant;Guidelines;Health;health care disparity;health care service utilization;health disparity;health equity;health equity promotion;Health Expenditures;health literacy;Health Personnel;Health Policy;Health Sciences;Healthcare;implementation research;implementation science;implementation study;improve minority health;improved;Incidence;Institution;Insurance;Intervention;Interview;Journals;K-Series Research Career Programs;Knowledge;Laboratories;Leadership;Measures;Medicine;meetings;Mentors;Mentorship;Methods;Minority;Minority Groups;minority patient;Modeling;Outcome;Patient Care;patient oriented;patient population;patient response;Patient risk;patient variability;Patient-Centered Care;patient-clinician communication;Patients;Pharmaceutical Preparations;Pharmacogenomics;Pharmacotherapy;Physicians;Population;Population Heterogeneity;Population Sciences;precision medicine;preference;Preparation;Process;professor;programs;Provider;Race;Randomized;Research;Research Personnel;research to practice;Resources;response;Risk;Scientist;Series;side effect;skills;Structure;Surveys;Technology;Testing;Time;Training;Translational Research;Uncertainty;Universities;Work;Writing

PROJECT_TITLE: Health Equity and Risk Communication in Pharmacogenomics

STUDY_SECTION: GNOM

STUDY_SECTION_NAME: Genome Research Study Section[GNOM-G]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Diabetes;Digestive Diseases;Pediatric;Prevention

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: This is an application for the establishment of a Southern California Clinical Center to participate in the Type 1 Diabetes in Acute Pancreatitis Consortium, comprised of an expert team to carry out studies of the Consortium in Los Angeles County, the most populous and ethnically diverse county in the United States. Acute pancreatitis, one of the most frequent causes of hospitalization in the USA, greatly increases the risk of future development of diabetes, yet the type of diabetes is unclear. We propose studies to determine the metabolic mechanisms and the genetic, protein, and imaging signature of diabetes occurring after pancreatitis, which will provide the means to understand, prevent, and treat this form of diabetes.

PI_NAMEs: GOODARZI, MARK  (contact);PANDOL, STEPHEN J.

PROGRAM_OFFICER_NAME: UNALP-ARIDA, AYNUR

PROJECT_TERMS: acute pancreatitis;Address;Artificial Intelligence;artificial intelligence method;Autoantibodies;Autoimmune;Biological Assay;Blood;California;chronic pancreatitis;Clinical;clinical center;cohort;Collection;County;Data;Data Set;Defect;design;Development;Diabetes Mellitus;diabetes risk;Early identification;Endocrinology;Enrollment;Epidemiology;ethnic diversity;Etiology;experience;Fasting;Frequencies;Future;Gastroenterology;Genetic;Genetic Anticipation;Genetic Risk;genome wide association study;genome-wide;Genotype;Glucose;Goals;Health;high risk;Homeostasis;Hormonal;Hospitalization;Hospitals;Image;imaging biomarker;improved;Incidence;Individual;innovation;Insulin;Insulin Resistance;insulin secretion;Insulin-Dependent Diabetes Mellitus;Intake;intravenous glucose tolerance test;islet;islet autoimmunity;islet cell antibody;Liquid substance;Los Angeles;Magnetic Resonance Imaging;Measures;Mediator;Meta-Analysis;Metabolic;Methods;Modeling;MRI Scans;Necrosis;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;Pancreas;pancreas imaging;Pancreatitis;Participant;Patients;Phenotype;Physiological;Physiology;predictive marker;predictive modeling;prevent;Preventive;prospective;Proteins;Proteomics;Protocols documentation;Public Health;recruit;Recurrence;Research;Research Personnel;response;Risk;Risk Factors;Sampling;Scanning;Set protein;Severities;Signal Transduction;Swelling;Testing;Therapeutic;type I and type II diabetes;United States;X-Ray Computed Tomography

PROJECT_TITLE: Southern California Clinical Center of the Type 1 Diabetes in Acute Pancreatitis Consortium


ORG_CITY: BRONX

ORG_NAME: JAMES J PETERS VA  MEDICAL CENTER

PHR: PROJECT NARRATIVE Older Veterans, particularly those with multiple chronic conditions requiring complex medication regimens, are more susceptible to adverse effects of medications. In this study, we examine the effect of a pharmacist led medication management intervention delivered by home televisit on improving medication use. We anticipate that a pharmacist led medication management intervention will lead to reduction in medication discrepancies and inappropriate use, increased medication adherence and reduced adverse drug events in older adults compared to those without the intervention and receiving usual care. Findings will enhance our understanding of methods to improve medication use in older adults, and have the potential to disseminate across VHA.

PI_NAMEs: HUNG, WILLIAM W.,MPH, MD (contact);MOO, LAUREN R

PROJECT_TERMS: Adherence;Adverse drug event;Adverse effects;Caring;Chronic Disease;Client satisfaction;Clinic;Clinical;Clinical Pharmacists;Complex;Data;design;Drug Interactions;Drug usage;Education;Effectiveness;effectiveness evaluation;effectiveness/implementation study;future implementation;Home;Hybrids;implementation evaluation;Improve Access;improved;information gathering;Intervention;Interview;Long-Term Care;Measures;medication compliance;Medication Management;medication nonadherence;Methods;multiple chronic conditions;Non-Prescription Drugs;older adult;Older Population;Outcome;Patients;Persons;Pharmaceutical Preparations;Pharmacists;Pharmacy facility;post intervention;Predisposition;primary outcome;Procedures;Protocols documentation;Provider;Quality of Care;Questionnaires;randomized trial;Randomized, Controlled Trials;Regimen;Research Design;Research Personnel;Respondent;Right to Treatments;Screening procedure;secondary outcome;Site;Structure;success;telehealth;Telemedicine;televisit;treatment as usual;uptake;Veterans;video visit;Visit;Visualization;Writing

PROJECT_TITLE: Effect of Medication Management at Home via Pharmacy Home Televisits

STUDY_SECTION_NAME: HSR-6 Aging, Recovery, and Workforce[HSR6]


NIH_SPENDING_CATS: Cancer;Data Science;Networking and Information Technology R&D (NITRD)

ORG_CITY: PROVIDENCE

ORG_NAME: RHODE ISLAND HOSPITAL

ORG_STATE: RI

PHR: Project Narrative The treatment of cancer is very complex, with thousands of treatment options across hundreds of types of cancer. In order to organize this information in a way that is usable for healthcare providers and translational researchers, we created the HemOnc.org knowledgebase, which is now the largest resource of its kind. This project seeks to maintain and enhance HemOnc.org for the benefits of clinicians, researchers, and patients.

PI_NAMEs: WARNER, JEREMY LYLE (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Adopted;American Association of Cancer Research;anti-cancer;anti-cancer treatment;Antineoplastic Agents;base;cancer care;Cancer Death Rates;cancer subtypes;cancer therapy;cancer type;cBioPortal;chemotherapy;Clinical Trials;Communities;comparative efficacy;Complex;Computer software;cooperative study;Country;Data;Data Reporting;Data Science;Databases;dosage;Dose;Drug usage;Elderly;experience;Feedback;Funding;GENIE;Goals;Graph;Growth;Guidelines;health data;Health Personnel;Health Professional;Hematology;Human Resources;Individual;Informatics;information organization;Institution;Knowledge;Knowledge Management;knowledgebase;Literature;Malignant Neoplasms;Maps;Meta-Analysis;Modeling;Monograph;NCI Thesaurus;Oncology;Ontology;Output;patient engagement;Patients;Pharmaceutical Preparations;Pharmacists;prevent;Professional Organizations;prospective;Protocols documentation;Publishing;racial minority;Recording of previous events;Regimen;repository;Research Personnel;Resources;Schedule;Site;SNOMED Clinical Terms;Source;Structure;success;Supportive care;symposium;System;Systematized Nomenclature of Medicine;therapy development;Time;Translational Research;translational scientist;treatment comparison;Treatment Protocols;Underrepresented Populations;United States Food and Drug Administration;Update;usability;Variant;Visit;Vocabulary;web site;Work

PROJECT_TITLE: Enhancing the HemOnc Knowledgebase of Chemotherapy Drugs and Regimens

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


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Social Determinants of Health

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE The non-communicable diseases diabetes, hypertension, and dyslipidemia are highly prevalent among people living with HIV (PWH), especially among multiply marginalized populations such as racial/ethnic minorities. We will study how intersecting stigmas contribute both directly and indirectly to the incidence, prevalence, and control of this comorbidity cluster in a diverse cohort of HIV positive and HIV negative sexual minority men. Our findings will provide valuable data for health providers, public health researchers, and policymakers to more effectively intervene across the complex pathways between marginalized social position, stigma, psychosocial health, and non-communicable disease outcomes.

PI_NAMEs: FRIEDMAN, MACKEY R (contact)

PROGRAM_OFFICER_NAME: COADY, SEAN

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adherence;Aging;antiretroviral therapy;Area;Biological Markers;biopsychosocial;Blood;care outcomes;Caring;Chronic;classism;cohort;Cohort Studies;comorbidity;Complex;Continuity of Patient Care;Data;Development;Diabetes Mellitus;Disease;Disease Outcome;disorder control;Disparity;Dyslipidemias;ethnic minority;Ethnic Origin;experience;Health;Health Care Rationing;health care settings;health data;health disparity;Health Personnel;Healthcare;Heart;HIV;HIV Seronegativity;HIV Seropositivity;Homophobia;Hypertension;improved;Incidence;Inequity;intersectionality;Intervention;intimate partner violence;Lung;marginalization;marginalized population;Mediating;Mediator;men of color;men who have sex with men;Mental Depression;middle age;minority stressor;National Heart, Lung, and Blood Institute;Outcome;Pathway interactions;Patients;perceived stress;Persons;Policies;Policy Maker;Population;Prevalence;prospective;protective factors;Provider;psychosocial;Psychosocial Assessment and Care;Public Health;Race;racial minority;racism;remediation;Research;Research Personnel;resilience;Running;sexual minority;sexual minority men;Sleep;social;social disparities;Social status;social stigma;socioeconomic disparity;Stress;substance use;success;Surveys;syndemic;therapy adherence;therapy design;United States National Institutes of Health;Violence;Viral;Work

PROJECT_TITLE: Stigma and the non-communicable disease syndemic in aging HIV positive and HIV negative MSM


NIH_SPENDING_CATS: Infectious Diseases;Malaria;Pediatric;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE Malaria is a leading cause of illness and death for children under five years of age globally, with most of these deaths resulting from infection by the Plasmodium falciparum parasite. The goal of this application is to improve our understanding of how the parasite divides during the clinically important blood stage of its life cycle. The studies will evaluate the function of two essential proteins that are hypothesized to organize parasite cell division.

PI_NAMEs: DVORIN, JEFFREY D (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: 5 year old;Anti-malarials;Apical;asexual;Binding Proteins;Biochemical;Biological;Biological Assay;Blood;Cell division;Cell membrane;Cell Nucleus;Cells;Cellular biology;Centrosome;Cessation of life;Child;Clinical;Co-Immunoprecipitations;combat;Complement;Complex;Critical Pathways;Culicidae;Cytokinesis;Cytoplasm;Cytoskeleton;Data;Daughter;daughter cell;Defect;Development;Dimerization;Ensure;Enterobacteria phage P1 Cre recombinase;Erythrocytes;Family;Fiber;Filament;Flagella;Foundations;Future;Generations;Genetic;Genome;genome-wide;Goals;Homologous Gene;Human;Immunofluorescence Immunologic;improved;Individual;Infection;Insecticides;kinetosome;knock-down;Knock-out;Knowledge;Label;Life Cycle Stages;live cell microscopy;Location;Malaria;Membrane;Methods;Microscopy;Microtubule-Organizing Center;Microtubules;Molecular;Morbidity - disease rate;Morphology;mortality;novel;Nuclear;nuclear division;Organelles;Orthologous Gene;Parasite resistance;Parasites;Pathway interactions;Plasmodium;Plasmodium falciparum;Process;Protein Family;protein protein interaction;Proteins;Publishing;Reporting;Resistance;Role;Series;Signs and Symptoms;Sirolimus;Structure;Techniques;Testing;Toxoplasma gondii

PROJECT_TITLE: Functional characterization of striated fiber assemblins in malaria parasites

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IIDA-F(02)]


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Inflammatory Bowel Disease;Microbiome

ORG_DEPT: PATHOLOGY

PHR: PROJECT NARRATIVE This project outlines plans to identify enzymes produced by gut bacteria that play important roles in the progression and maintenance of inflammatory bowel disease (IBD) and that could be targeted for therapeutic purposes.

PI_NAMEs: BOGYO, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: activity-based protein profiling;Affect;Bacteria;Bacterial Toxins;Biochemical;Biological;Biological Assay;Biology;Body Weight decreased;Caco-2 Cells;Cell Culture System;Cell model;Cells;chemical synthesis;Chemicals;Clinical;Collection;commensal bacteria;Crohn's disease;Data;desensitization;Diarrhea;Disease;Enzymes;Epithelium;Event;extracellular;F2R gene;Fatigue;fluorescein isothiocyanate dextran;Fractionation;Future;G-Protein-Coupled Receptors;gastrointestinal;Gastrointestinal Diseases;Gene Expression;Goals;gut bacteria;gut dysbiosis;gut homeostasis;gut microbiome;gut microbiota;Health;host-microbe interactions;Human;Human Cell Line;in vitro Assay;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inhibitor;intestinal barrier;intestinal epithelium;Ligands;Link;liquid chromatography mass spectrometry;Maintenance;Maps;Measures;Mediating;microbial;Microbiology;Modeling;Molecular Conformation;monolayer;N-terminal;new therapeutic target;novel;Nutrient;Organoids;Pain;pathobiont;Pathogenesis;pathogenic bacteria;Pathology;Patients;Peptide Hydrolases;Permeability;Phenotype;Physiological;Play;Positioning Attribute;prevent;Process;Protease Inhibitor;protein aminoacid sequence;protein expression;Proteinase-Activated Receptors;Proteolysis;Proteomics;Qualifying;receptor;Receptor Activation;Receptor Signaling;Reporter;Role;Sampling;screening;Signal Transduction;Site;small molecule;success;Symptoms;targeted treatment;Testing;Therapeutic;therapeutic target;Tissues;Ulcerative Colitis;Work

PROJECT_TITLE: Targeting bacterial proteases involved in PAR signaling to treat inflammatory bowel diseases

STUDY_SECTION: SBCB

STUDY_SECTION_NAME: Synthetic and Biological Chemistry B Study Section[SBCB]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Orphan Drug;Rare Diseases

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Project Narrative  Angioimmunoblastic T-cell lymphomas (AITL) derived from follicular helper T-cell (TFH) cells is associated with an aggressive clinical course with poor outcome. Two major genetic events (i.e.TET2 loss and oncogenic IDH2 mutations) play key pathogenic roles in malignant T-cell transformation, modulation of the tumor microenvironment and deregulated TFH differentiation in AITL through alteration of the epigenome. Using genetically faithful murine models, patient derived xenografts (PDX), genetically modified human CD4+T-cells and AITL specimens, we will delineate the driver pathogenic events that are amenable to effective therapies, ultimately leading to better clinical-outcome in AITL patients.

PI_NAMEs: CHAN, WING C.;IQBAL, JAVEED  (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: accurate diagnosis;Affect;Aggressive Clinical Course;Arginine;CD28 gene;CD4 Positive T Lymphocytes;Cell Differentiation process;Cell Line;Cell model;cell transformation;Cells;Characteristics;Clinical;Clonal Expansion;CRISPR/Cas technology;demethylation;Development;Diagnosis;disease prognosis;DNA;DNA Methylation;DNMT3a;drug efficacy;effective therapy;efficacy study;efficacy testing;Enzymes;Epigenetic Process;epigenome;epigenomics;Event;Family member;Gene Expression;Gene Expression Profiling;Gene Modified;Gene Mutation;Genes;Genetic;genome-wide;Genomics;Glutamine;Goals;Helper-Inducer T-Lymphocyte;Hematologic Neoplasms;Hematopoiesis;Hematopoietic stem cells;histone demethylase;Human;human model;Immunoblastic Lymphadenopathy;Immunophenotyping;In Vitro;Induced Mutation;inhibitor;insight;Knockout Mice;Lesion;loss of function mutation;Lymphoma;Lymphomagenesis;Malignant - descriptor;Malignant lymphoid neoplasm;Mediating;Metabolic;Modification;Molecular;mouse model;Mus;mutant;mutant mouse model;Mutation;Myeloid Cells;Myeloproliferative disease;neoplastic;neoplastic cell;novel;novel therapeutic intervention;novel therapeutics;Oncogenic;Outcome;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;patient derived xenograft model;Patients;Peripheral;Phenotype;Play;polarized cell;pre-clinical;Pre-Clinical Model;Preclinical Testing;Production;programs;Research;RHOA gene;Role;Sampling;Specimen;Stromal Cells;System;T cell differentiation;T-Cell Activation;T-Cell Development;T-Cell Lymphoma;T-Cell Transformation;T-Lymphocyte;targeted treatment;Testing;therapeutic evaluation;Therapeutic Intervention;Transgenic Organisms;treatment response;tumor;tumor microenvironment;Validation

PROJECT_TITLE: Cooperative role of TET2 and IDH2 mutations in angioimmunoblastic T-cell lymphomagenesis

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging

ORG_DEPT: CHEMISTRY

ORG_NAME: OHIO STATE UNIVERSITY

PHR: Project Narrative Developing new ways of noninvasively imaging the chemistry of the body is a grand challenge in biomedical imaging. High-spin metal complexes may enable such imaging through the electron analogue to conventional magnetic resonance imaging (MRI) but have not yet been developed for this technique. This proposal will do so, in the process creating a transformative new class of molecular imaging probes.

PI_NAMEs: ZADROZNY, JOSEPH M (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Amendment;analog;Anatomy;biomedical imaging;body map;Chemicals;Chemistry;Dangerousness;design;Electron Spin Resonance Spectroscopy;Electronics;Electrons;Frequencies;Functional Imaging;Goals;Hybrids;Image;imaging probe;Inorganic Chemistry;Ions;Knowledge;Laboratories;magnetic field;Magnetic Resonance Imaging;Maps;meetings;metal complex;Metals;microwave electromagnetic radiation;Modernization;molecular imaging;Molecular Probes;non-invasive imaging;Physiological;Process;Property;Resolution;System;Techniques;Work

PROJECT_TITLE: New Classes of Electron Paramagnetic Resonance Imaging Probes With High-Spin Metal Complexes


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Prevention;Rare Diseases

ORG_CITY: DURHAM

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: NARRATIVE The proposed research will develop a low-cost, easy-to-use, and highly sensitive point-of-care clinical diagnostic for Ebola virus—the D4 assay—with an antibody pair that binds with a new protein biomarker of Ebola. In this assay, a drop of blood is added to the surface of a protein and cell-resistant polymer film, which dissolves fluorescently labeled detection antibodies that are printed as “soluble” spots that then diffuse and bind to “stable” spots of capture antibodies. The chip is encased in a microfluidics cassette that runs the assay without user intervention and is read by a handheld detector that images the fluorescence spots and gives a result in 30 minutes.

PI_NAMEs: CHILKOTI, ASHUTOSH  (contact)

PROGRAM_OFFICER_NAME: DYALL, JULIE

PROJECT_TERMS: 3-Dimensional;Address;Adsorption;Affinity;Antibodies;Antibody Affinity;antibody detection;Binding;Biological Assay;Blood;Blood capillaries;Blood specimen;Body Fluids;Capillarity;Cartoons;Cell model;Cells;Clinical;clinical diagnostics;Communicable Diseases;cost;design;Detection;detection limit;detector;Development;Devices;Diagnosis;Diffuse;Diffusion;Disease Outbreaks;Dissociation;Drops;Early Diagnosis;Ebola;Ebola virus;Enzyme-Linked Immunosorbent Assay;Epidemic;Epitopes;Equilibrium;Equipment;Exposure to;Film;Fluorescence;fluorescence imaging;frontier;Glass;Glycoproteins;Goals;Health Personnel;high throughput screening;Human;Human Resources;Image;imaging detector;imaging platform;improved;Incubated;Infection;Infection Control;Infrastructure;Intervention;Label;Laboratories;lateral flow assay;Macaca;Macaca fascicularis;Macaca mulatta;Measures;Methods;Microfluidic Microchips;Microfluidics;Modeling;Monkeys;Monoclonal Antibodies;Mutate;nonhuman primate;Output;Patients;Performance;Pharmaceutical Preparations;point of care;point of care testing;Polymers;portability;Power Sources;Printing;protein biomarkers;Proteins;prototype;Reader;Reagent;Research;Resistance;Reverse Transcriptase Polymerase Chain Reaction;RNA;Running;Sampling;Secure;Serum;skills;Speed;Spottings;Sudan;Surface;Survival Rate;synergism;Techniques;Technology;Testing;Time;Time Study;Training;Translating;user-friendly;Viral;viral detection;Viral Proteins;viral RNA;Viremia;virtual;Virus Diseases;wireless transmission;Zaire Ebola virus

PROJECT_TITLE: A Fully Integrated Point-of-Care Test for Ebola

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


ADMINISTERING_IC: AT

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Complementary and Integrative Health;Digestive Diseases;Liver Disease;Mental Health;Neurosciences;Nutrition;Substance Misuse

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Narrative: Functional mapping of liver-innervating vagal sensory neurons will fill in some basic gaps in our knowledge of the vagal sensory system that control hepatic glucose metabolism. Our findings will lay the foundation for future translational studies to tackle significant issues in human health, including diabetes and obesity.

PI_NAMEs: JO, YOUNG-HWAN  (contact)

PROGRAM_OFFICER_NAME: CHEN, WEN G

PROJECT_TERMS: Adaptive Behaviors;Afferent Neurons;anatomical tracing;Anatomy;Animals;Appetite Stimulants;Autonomic nervous system;AVIL gene;awake;Behavior;Behavioral;Bipolar Disorder;Blood Glucose;blood glucose regulation;Brain;Brain Stem;Calcitonin Gene-Related Peptide;Cell Nucleus;cell type;Cells;cholinergic;Desire for food;detection of nutrient;Diabetes Mellitus;Dinoprostone;Disease;Dopamine;dorsal motor nucleus;Eating;Eating Behavior;Emotions;experience;experimental study;falls;feeding;Feeding behaviors;Feeling;Foundations;Future;gamma-Aminobutyric Acid;gastrointestinal system;Gene Expression;Genes;Gluconeogenesis;Glucose;glucose metabolism;glucose output;glucose production;glycogenolysis;Health;Hepatic;Homeostasis;Hormonal;Hormones;Human;Hypothalamic structure;Immune;in vivo calcium imaging;increased appetite;Individual;inhibitory neuron;interest;Knowledge;Kupffer Cells;Liver;liver ablation;loss of function;LTB4R gene;Lung;Maps;Mental Depression;Mental disorders;Mixed Function Oxygenases;Molecular;Moods;Motivation;Motor Neurons;Mus;Nerve;neural;neural circuit;Neural Pathways;neurochemistry;Neurons;Neuropeptide Y Receptor;Neuropeptides;Neurotransmitters;Nodose Ganglion;Norepinephrine;novel;Nutrient;Obesity;optogenetics;Organ;Pancreas;parabrachial nucleus;Parasympathetic Nervous System;Pathway interactions;Peripheral;Physiological;Pilot Projects;Play;Population;protachykinin;psychologic;Purinoceptor;purinoceptor P2Y1;receptor;Regulation;Rewards;Role;Sensory;sensory system;Signal Transduction;single-cell RNA sequencing;Sodium Channel;Specificity;Structure;Structure of nucleus infundibularis hypothalami;Subgroup;Substance abuse problem;Sympathetic Nervous System;Synapses;Techniques;transcriptome sequencing;translational study;transmission process;Transportation;Vagus nerve structure;Vasoactive Intestinal Peptide

PROJECT_TITLE: Functional identification of vagal sensory neurons innervating the liver


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

ORG_CITY: DAVIS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative – Overall Acute intoxication with organophosphate (OP) pesticides or nerve agents can trigger seizures that rapidly progress to life-threatening status epilepticus, and survivors often experience significant long-term morbidity, including progressive brain injury, spontaneous recurrent seizures, and cognitive impairment. Current medical countermeasures for acute OP intoxication can prevent death, but are unable to fully protect against the long- term adverse neurological consequences unless administered within minutes of exposure, which is an unlikely scenario in the event of accidental, suicidal or terrorist-related exposures. The UC Davis CounterACT Center of Excellence seeks to identify and develop novel disease-modifying therapeutic strategies that can be administered in hours to months after exposure to delay the onset and/or reduce the severity of chronic neurotoxic effects.

PI_NAMEs: BROOKS-KAYAL, AMY R.;LEIN, PAMELA J (contact)

PROGRAM_OFFICER_NAME: SPRIGGS, SHARDELL M

PROJECT_TERMS: Accidents;Acute;Address;Adult;Analytical Chemistry;Area;Atropine;Automobile Driving;Behavioral;Benzodiazepines;Biological Markers;biomarker identification;blood-brain barrier function;Brain;Brain Injuries;Calpain;candidate identification;Cessation of life;cholinergic;Cholinesterase Inhibitors;Chronic;Clinical;combinatorial;Data;Data Analyses;Deep Brain Stimulation;Detection;Development;Disease;education research;Electrophysiology (science);Epilepsy;Epoxide hydrolase;equity, diversity, and inclusion;Event;experience;Experimental Designs;Exposure to;FDA approved;Female;forging;Formulation;Goals;Hour;Human;Image;Impaired cognition;Impairment;improved;in vivo;indexing;Individual;Industrial Accidents;Inflammation;innovation;Intellectual Property;Interleukin-1 beta;Intervention;Intoxication;Ion Channel;Isoflurophate;Learning;Life;Link;male;mass casualty;medical countermeasure;meetings;Memory;Mentors;Modeling;Molecular;Morbidity - disease rate;mortality;multidisciplinary;nerve agent;Nerve Degeneration;Nervous System Physiology;neuroimaging;neuroinflammation;Neurologic;Neurologic Effect;Neurological outcome;neuronal excitability;neuropathology;neurotoxic;neurotoxicity;new therapeutic target;novel;novel therapeutic intervention;novel therapeutics;Organophosphates;Outcome;Oximes;Pathogenesis;Pathogenicity;Pathway interactions;Pesticides;Pharmaceutical Chemistry;pharmacologic;Phase;Pilot Projects;Plasminogen Activator Inhibitor 1;pre-clinical;Pre-Clinical Model;preclinical study;predictive marker;prevent;programs;Rattus;recruit;Recurrence;Research;Research Personnel;Research Project Grants;response;Risk;Rodent;Science;Scientist;Seizures;Severities;Signal Transduction;small molecule inhibitor;Soman;standard of care;statistics;Status Epilepticus;suicidal;Survivors;Testing;Therapeutic;therapeutic candidate;Toxic effect;Training;Translating;United States National Institutes of Health

PROJECT_TITLE: UC Davis CounterACT Center of Excellence: Developing Therapeutic Strategies for Mitigating the Chronic Neurological Consequences of Acute Organophosphate Intoxication

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-P(50)]