ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Ischemia-reperfusion injury is the basic mechanism of tissue damage underlying many important diseases to veterans’ health. These include heart attack and stroke. In the lung, ischemia-reperfusion injury manifests as acute respiratory distress syndrome and primary graft dysfunction, two morbid and prevalent lung diseases without known therapies. Our veterans suffer disproportionately from end stage lung disease, making the improvement of lung transplant outcomes a vital mission. Thus, there is a critical need to develop new treatments. This proposal focuses on a novel mechanism of pulmonary ischemia-reperfusion injury in an understudied innate immune cell, the natural killer cell. Our data suggest a new and central role for natural killer cells that shifts our understanding of this disease process. This study employs cutting edge technologies to answer the fundamental questions of how NK cells cause this lung injury and how they traffic to the lung. These findings may lead to a better understanding of this process and novel therapeutic modalities targeting NK cells for veterans’ benefit.

PI_NAMEs: CALABRESE, DANIEL  (contact)

PROJECT_TERMS: Activated Natural Killer Cell;Acute Lung Injury;Acute Respiratory Distress Syndrome;Allografting;Antibodies;Area;Award;Bioinformatics;Blood Cells;Bronchoalveolar Lavage Fluid;California;candidate selection;career;career development;CCR5 gene;Cell Maturation;Cell surface;Cells;Cellular biology;chemokine;chemokine receptor;Chest;Clinical;Clinical Research;Clinical Trials;Closure by clamp;cohort;Collaborations;Color;Critical Care;Cryopreservation;CXCR3 gene;cytokine;Cytometry;cytotoxicity;Data;Disease;Endothelium;epidemiology study;Epithelium;experience;Experimental Models;Flow Cytometry;Foundations;Frequencies;Functional disorder;Funding;Future;Genetic;Goals;graft dysfunction;Greenland;Health;Hilar;Human;human disease;human model;Hypoxia;Immune;Immunity;Immunodeficient Mouse;Immunology;improved;Individual;Inflammatory Bowel Diseases;Injury;innate immune mechanisms;Innate Immune Response;innovation;Institution;Interferon Type II;International;Intervention;Intervention Trial;Ischemia;Ischemic Stroke;Laboratory Scientists;Ligands;Lung;lung allograft;Lung Diseases;lung injury;lung ischemia;Lung Transplantation;Macrophage;Measures;Mediating;Mentors;Mentorship;Mission;Modality;Modeling;Monoclonal Antibodies;monocyte;mouse model;Mus;Myocardial Infarction;Natural Killer Cells;Neutrophil Infiltration;new therapeutic target;next generation;NK Cell Activation;Nonpenetrating Wounds;novel;novel therapeutics;Outcome;Pathology;Pathway interactions;Patients;perforin;peripheral blood;Phenotype;Physicians;pre-clinical;Process;professor;programs;prospective;Proteins;PTPRC gene;Publications;receptor;Receptor Cell;Receptor Signaling;reconstitution;Reperfusion Injury;Reperfusion Therapy;Research;Research Personnel;response;Risk;Role;Sampling;San Francisco;Series;skill acquisition;skills;Stress;Stroke;Surgical Models;Syndrome;Technology;Testing;Time;Tissues;trafficking;translational scientist;Transplant Recipients;Transplantation;Universities;Veterans;Warm Ischemia;Wild Type Mouse;Work

PROJECT_TITLE: Natural killer cells in pulmonary ischemia-reperfusion injury


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: Veterans Affairs

ORG_CITY: INDIANAPOLIS

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: RLR VA MEDICAL CENTER

ORG_STATE: IN

PHR: Project Narrative Lung cancer remains the leading cause of cancer deaths in the United States. This is particularly concerning for U.S. veterans, who are at an increased risk for lung cancer, from which 5,500 veterans die each year. Cancers often have abnormalities in their ability to repair DNA damage, which we believe are important to the development of mutations and other characteristic changes or lung cancer. Our laboratory has found a critical role of the DNA repair protein, Xeroderma Pigmentosum Group C (XPC) in protection against non-small cell lung cancer development. Using mouse carcinogen models of lung cancer and human lung cancer samples, we will look at the impact of DNA repair and XPC specifically on the earliest genetic changes and response to immunotherapy in non-small cell lung cancer. The ultimate goal is to find targets to identify non-small cell lung cancer earlier and treatments to prevent pre-cancerous lesions from progressing to lung cancer.

PI_NAMEs: SEARS, CATHERINE RUFATTO (contact)

PROJECT_TERMS: Acceleration;Adenocarcinoma;Archives;Atypical adenomatous hyperplasia;Benign;Biological Assay;Biological Markers;bronchial epithelium;Cancer Etiology;carcinogenesis;Carcinogens;Carcinoma;Cells;Cessation of life;Characteristics;chest computed tomography;Chronic;cigarette smoke;Complex;Data;Detection;Development;Diagnosis;Diagnostic;Disease;DNA Repair;DNA Repair Gene;DNA Repair Pathway;Dysplasia;Early Diagnosis;Early identification;Early treatment;Environment;Epigenetic Process;Epithelial Cells;Ethics;Evolution;Excision;exposure to cigarette smoke;Gene Expression;genome sequencing;genomic data;Genomic Instability;Genomics;Goals;Head and neck structure;high risk;Histologic;Histopathologic Grade;Human;Human Characteristics;Immune;Immune Evasion;Immunologics;Immunophenotyping;Immunotherapy;improved;In Vitro;in vivo;Indolent;inter-individual variation;interest;Intervention;Intraepithelial Neoplasia;Knowledge;Laboratories;Lesion;low dose computed tomography;Lung;Lung Adenocarcinoma;lung cancer screening;lung carcinogenesis;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;Masks;Modeling;mortality;Mus;Mutation;new therapeutic target;Nodule;Non-Small-Cell Lung Carcinoma;Operative Surgical Procedures;Pathologic;patient population;Patients;Pattern;PDL1 inhibitors;personalized diagnostics;personalized medicine;Physiological;predictive signature;premalignant;prevent;programmed cell death ligand 1;Public Health;Recommendation;Relative Risks;Resistance;response;Risk;Risk Reduction;Role;Sampling;screening;single cell sequencing;Specimen;Squamous Cell;Squamous Cell Lung Carcinoma;Therapeutic;Therapeutic Intervention;therapeutic target;tool;transcriptomics;Treatment Efficacy;tumor;United States;Urethane;Validation;Veterans;whole genome;Xeroderma pigmentosum group C

PROJECT_TITLE: Characterization of DNA repair in genomic and transcriptomic evolution of early lung carcinogenesis


ORG_CITY: CHICAGO

ORG_NAME: JESSE BROWN VA MEDICAL CENTER

ORG_STATE: IL

PHR: This project is the first major investigation of the role of the enzyme N-acetylgalactosamine-4- sulfatase, also known as arylsulfatase B (ARSB), in melanoma. A prior publication has shown that ARSB is reduced as melanomas progress in invasiveness. ARSB is required for removal of sulfate groups of chondroitin 4-sulfate (C4S) and for the degradation of C4S. In the absence of ARSB, C4S accumulates and affects the function of other critical molecules which bind to it, more or less depending on the sulfation. Changes in binding with C4S lead to transcriptional events, including increased expression of the melanoma specific proteoglycan CSPG4 and of pro-MMP2, which facilitates invasion of melanoma cells. This project addresses how decline in ARSB leads to increased PD-L1 and considers how modulation of ARSB may affect the progression of melanoma, impact on the response to checkpoint inhibition, and reduce morbidity and mortality.

PI_NAMEs: TOBACMAN, JOANNE KRAMER (contact)

PROJECT_TERMS: Address;Affect;anti-PD1 therapy;Apoptosis;Arylsulfatase B;Binding;Biological;Breast;cancer cell;Cardiac;CD34 gene;Cell Line;Cell Physiology;Cell Survival;Cells;Characteristics;checkpoint inhibition;checkpoint therapy;Chondroitin;Chondroitin Sulfate A;chondroitin sulfate glycosaminoglycan;Chondroitin Sulfate Proteoglycan;Clinical;Coculture Techniques;Colon;Dermatan Sulfate;Disease;Doctor of Medicine;Doctor of Philosophy;Dose;Early Diagnosis;Effectiveness;enzyme activity;Enzymes;Event;Excision;experience;experimental study;Family;Family member;Galectin 3;Gelatinase A;General Population;Genetic Transcription;Growth;Human;human tissue;humanized mouse;Immune;Immune checkpoint inhibitor;immunomodulatory therapies;Immunooncology;Implant;improved;insight;Insulin Receptor;interest;Invaded;Investigation;knock-down;Knockout Mice;Lead;lead sulfate;Liver;Lymphocyte;Lysosomal Storage Diseases;Malignant Neoplasms;MAP Kinase Gene;MAPK3 gene;MAPK8 gene;Matrix Metalloproteinases;Measures;Mediator;melanocyte;Melanoma;Melanoma Cell;Metastatic Melanoma;MMP2 gene;Modification;Morbidity - disease rate;mortality;mouse model;Mucopolysaccharidosis VI;Mus;Mutation;Neurologic;novel;novel strategies;novel therapeutic intervention;Nuclear Translocation;Oncologist;Orthopedics;overexpression;p38 Mitogen Activated Protein Kinase;Pathology;Patients;pembrolizumab;Phosphorylation;polysulfated glycosaminoglycan;programmed cell death ligand 1;Prostate;Protein Dephosphorylation;Protein Tyrosine Phosphatase;Proteoglycan;PTPN11 gene;Publications;Publishing;Radial;Recombinants;Recurrence;Reporting;Research Personnel;respiratory;response;Role;Signal Transduction;Signaling Molecule;Stage at Diagnosis;Structure;Sulfatases;Sulfate;Testing;Time;Tissue Microarray;Tissues;Toxic effect;Transcription Coactivator;transcription factor;transcriptome sequencing;Treatment Effectiveness;Treatment Protocols;Veterans;Work;Xenograft Model

PROJECT_TITLE: Impact of N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on the Progression of Melanoma


ORG_CITY: NORTH LITTLE ROCK

ORG_NAME: CENTRAL ARKANSAS VETERANS HLTHCARE SYS

ORG_STATE: AR

PHR: PROJECT NARRATIVE Prostate cancer (PCa) is a major health issue among military veterans in the United States. Environmental exposures during deployment and post-deployment likely have significant impacts on PCa risk in veterans. Inorganic arsenic (iAs) and lead (Pb) are classified as a carcinogen/potential carcinogen in humans. The post- deployment demographic data and occupations suggest a potential risk for veterans to be exposed to metals, such as iAs and Pb, in environmental as well as occupational settings. However, the underlying molecular mechanisms that link metal exposure and prostate cancer are understudied. This application will test the hypothesis that iAs or Pb transforms prostate epithelial stem-like cells to initiate or increase PCa risk in a mouse models. Our findings with a novel approach of single cell RNA-seq will reveal this rare epithelial stem cell population in the adult prostate as the possible origin of metal-associated prostate cancer, and provide novel specific biomarkers that will advance our current strategies in assessing the risk and treating the human disease.

PI_NAMEs: HO, SHUK-MEI  (contact)

PROJECT_TERMS: Address;Adult;Agar;Air;Animal Model;Animals;anti-cancer research;Apoptotic;Applications Grants;Arsenic;Biological Assay;cancer diagnosis;Cancer Patient;cancer risk;cancer stem cell;carcinogenesis;carcinogenicity;Carcinogens;Carcinoma;Categories;Cell Lineage;Cell Separation;cell transformation;Cells;chemical carcinogen;Chemicals;Classification;Clinic;Clinical Research;clinically significant;cohort;Data;Databases;design;Development;Diagnosis;disability;disorder prevention;DNA Damage;Dose;drinking water;Drug Targeting;Environment;Environmental and Occupational Exposure;Environmental Exposure;Epithelial Cells;epithelial stem cell;Epithelium;Exposure to;Foundations;Future;Gene Expression;genetic signature;Genomic Instability;Gland;Goals;hazard;Health;Healthcare;Human;human disease;Immunocompetence;immunodeficiency;improved;in vivo;in vivo Model;Incidence;Informatics;Ingestion;Inhalation;insight;International Agencies;Ions;Kidney Transplantation;Knowledge;Lead;lead exposure;Lead levels;Lesion;Link;male;Malignant neoplasm of prostate;Malignant Neoplasms;Metal Carcinogenesis;Metal exposure;Metals;metaplastic cell transformation;military service;military veteran;Molecular;Molecular Profiling;mouse model;Mus;neoplasm registry;novel;novel strategies;Occupational;Occupations;Oncogenic;Phenotype;Physiological;Pilot Projects;Population;precision genomic medicine;precision medicine;Predisposition;premalignant;prevent;Probability;Prostate;prostate cancer model;prostate cancer prevention;prostate cancer risk;prostate carcinogenesis;Public Domains;Reporting;Resistance;Risk;Risk Assessment;Risk Factors;Signal Pathway;single-cell RNA sequencing;specific biomarkers;stem cell biology;stem cell biomarkers;stem cell division;stem cell niche;stem cell population;stem cells;stem-like cell;stemness;Survival Analysis;System;Testing;The Cancer Genome Atlas;Therapeutic;transcriptome;transcriptomics;trend;understudied cancer;United States;United States Department of Veterans Affairs;Universities;Urine;Urology;Veterans;Visit;Visualization;Work

PROJECT_TITLE: Metal-induced cell-level changes in prostate epithelium and cancer risk


ADMINISTERING_IC: HD

IC_NAME: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT

NIH_SPENDING_CATS: Bioengineering;Contraception/Reproduction;Infertility;Pediatric;Pregnancy;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

ORG_STATE: CA

PHR: This research will shed light on a poorly understood but critical period of mammalian development that spans the embryo's implantation into the uterus, the period when many human pregnancies terminate, and thus will yield clinically relevant discoveries in developmental and reproductive biology. The systems being developed will form the basis of approaches to decipher how pathogens, toxins and teratogens affect early development, and so will have environmental and drug safety value. Moreover, as this research utilizes stem cell biology to drive the formation and development of synthetic embryo-like structures, it is expected to inform regenerative medicine applications for a wide range of diseases.

PI_NAMEs: ZERNICKA-GOETZ, MAGDALENA  (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Affect;Assisted Reproductive Technology;blastocyst;Chemicals;clinically relevant;critical period;Development;Developmental Biology;Disease;drug testing;Embryo;embryo tissue;Embryonic Development;Endometrial;Engineering;Environment;Event;Exposure to;Extracellular Matrix;Fertility;Fostering;gastrulation;Gene Modified;Genetic Engineering;Human;Hydrogels;Implant;implantation;improved;in utero;In Vitro;innovation;insight;Investigation;Knowledge;Lead;Life;medication safety;Modeling;Molecular;Mothers;Mus;natural Blastocyst Implantation;Organogenesis;Organoids;pathogen;Placenta;pregnancy failure;preimplantation;Proteins;Regenerative Medicine;Reproductive Biology;Research;Route;Safety;screening;Signal Transduction;stem cell biology;stem cells;Structure;System;Teratogens;Termination of pregnancy;Time;Tissues;tool;Toxin;trophoblast;Uterus

PROJECT_TITLE: Placental models to support embryogenesis in vitro


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infant Mortality;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: LITTLE ROCK

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

PHR: PROJECT NARRATIVE  Despite the longstanding inequities in rates of low birthweight births among women of minority race, many public and private payers are unable to identify and mitigate disparities in adverse perinatal outcomes because of a lack of information on race and ethnicity. Information on race/ethnicity is necessary to build adequate prediction models for allocation of resources to prevent low birthweight births. This K01 aims to provide an evidence-base for collection and use of race/ethnicity by: 1) testing whether multiple algorithmic bias reduction approaches result in fairer low birthweight predictive models than models that exclude race/ethnicity, and 2) conducting community-engaged focus groups of Black, Hispanic, and Marshallese women to develop guidelines for how and when racial/ethnic data should be collected and used by public and private healthcare payers for use in perinatal health programs.

PI_NAMEs: BROWN, CLARE  (contact)

PROGRAM_OFFICER_NAME: STINSON, NATHANIEL

PROJECT_TERMS: Address;Adult;advanced analytics;adverse birth outcomes;adverse outcome;algorithm development;algorithmic bias;Algorithms;Arkansas;at-risk pregnancies;Attitude;Awareness;Behavioral;beneficiary;Big Data;Birth;Birth Certificates;Birth Weight;Black Populations;Black race;career;Classification;Clinical;Collection;Communities;community based participatory research;community engaged approach;community engagement;Competence;Data;Databases;Death Rate;Demographic Factors;Discrimination;Disparity;disparity elimination;disparity reduction;econometrics;Equity;ethnic disparity;Ethnic Origin;evidence base;evidence based guidelines;Exclusion;experience;Failure;Focus Groups;Fright;Geography;Goals;Guidelines;Health;health care delivery;health disparity;health management;health plan;Healthcare;High Risk Woman;Hispanic;improved;Inequity;infancy;Infant;Infant Health;Infant Mortality;infant outcome;information gathering;Infrastructure;Institute of Medicine (U.S.);Insurance Carriers;Insurance Claim Review;insurance claims;Intervention;Life Cycle Stages;Link;Logistic Regressions;long-standing disparities;Low Birth Weight Infant;Managed Care;maternal outcome;Measures;Medicaid;Medical;Methodology;Methods;Minority;Modeling;Native Hawaiian or Other Pacific Islander;Neurodevelopmental Disorder;Not Hispanic or Latino;Outcome;Patient Self-Report;Perinatal;perinatal health;perinatal outcomes;population health;prediction algorithm;Predictive Analytics;predictive modeling;Prejudice;premature;Prenatal care;prevent;Privatization;Productivity;programs;Provider;Publishing;Qualitative Research;Race;racial disparity;racial minority women;random forest;Recommendation;Reduce health disparities;Refit;regression algorithm;Reporting;Research;Research Methodology;Research Personnel;Resource Allocation;Respiration Disorders;Risk;Seminal;skill acquisition;skills;social factors;Techniques;Testing;Third-Party Payer;Training;White Women;Woman

PROJECT_TITLE: Algorithmic fairness in predictive models to eliminate disparities in adverse infant outcomes:  A case for race


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering

ORG_DEPT: PHYSICS

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE A fundamental challenge in modern cell biology is to understand how cells sense and process mechanical signals to alter their physiology. We propose a multi-disciplinary strategy to reveal the mechanism by which LIM domain proteins control mechanotransduction pathways in epithelial tissue. These experiments will elucidate the mechanism by which LIM domains bind to mechanically stressed actin filaments, the force-dependent sorting of LIM proteins to within adherent cells and control of YAP/TAZ mechanotransduction signaling by the LIM protein LIMD1 in epithelia.

PI_NAMEs: GARDEL, MARGARET LISE (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Actins;Adherens Junction;Affect;Affinity;Apoptosis;Atherosclerosis;Avidity;Binding;Biochemistry;Biophysics;cell behavior;Cell Physiology;Cell Proliferation;Cell Size;Cells;Cellular biology;Cellular Metabolic Process;Collaborations;Communication;Comparative Study;Cues;Cytoplasm;Cytoskeleton;Defect;Development;Disease;Elements;Environment;Epithelial Cells;Epithelium;Exhibits;experimental study;Family;Focal Adhesions;Heart failure;Hydrophobicity;In Vitro;innovation;insight;Investigation;Knowledge;LIM Domain;LIM Domain Protein;live cell imaging;Malignant Neoplasms;Mammalian Cell;mathematical model;Measures;mechanical force;mechanical signal;mechanical stimulus;Mechanical Stress;Mechanics;mechanotransduction;Methodology;Microfilaments;Modeling;Modernization;Molecular;Molecular Conformation;Monitor;Movement;multi-scale modeling;multidisciplinary;novel strategies;organ regeneration;Organelles;Pathway interactions;paxillin;Periodicals;Phenylalanine;Physiological;Physiology;Process;Protein Family;Proteins;reconstitution;recruit;Regulation;Series;Shapes;Signal Pathway;Signal Transduction;Sorting;Specificity;Stress;Stress Fibers;Surface;Testing;Tissues;transmission process;ZYX gene

PROJECT_TITLE: Mechanisms of Mechanotransduction by LIM Domain Proteins

STUDY_SECTION_NAME: Cell Structure and Function 1 Study Section[CSF1]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: SYDNEY

ORG_COUNTRY: AUSTRALIA

ORG_FIPS: AS

ORG_NAME: UNIVERSITY OF NEW SOUTH WALES

PHR: Project Narrative This application seeks renewal of funding for a Research Program for acute lymphoblastic leukemia (ALL) in vivo testing as part of the NCI Pediatric In Vivo Testing Program (Ped-In Vivo-TP). By completing the major objectives outlined in this proposal, the long term health benefit aims to improve the treatment options and quality of life for children with aggressive forms of ALL who would otherwise succumb to their disease.

PI_NAMEs: LOCK, RICHARD B (contact)

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Acceleration;Acute Lymphocytic Leukemia;Acute T Cell Leukemia;Adopted;Adult;Advisory Committees;animal imaging;Animals;B-Cell Acute Lymphoblastic Leukemia;bioluminescence imaging;Biopsy;Bone Marrow;Bone Marrow Aspiration;Cancer Patient;Cells;Characteristics;Child;Childhood;Childhood Acute Lymphocytic Leukemia;Clinic;Clinical;clinical development;Clinical Trials;cost estimate;Data;data submission;design;Diagnosis;Disease;Drug Combinations;Drug Kinetics;Drug Monitoring;Drug resistance;drug response prediction;drug testing;early phase clinical trial;Engraftment;Ensure;Evaluation;exome sequencing;experience;Experimental Models;experimental study;Exposure to;Failure;flexibility;follow-up;Foundations;Funding;Future;Gene Expression Profiling;Government;Health Benefit;Heterogeneity;high risk;Human;immunodeficiency;improved;improved outcome;in vivo;in vivo evaluation;Industry Collaboration;Infant;Infiltration;lentivirally transduced;Lesion;leukemia;Leukemia, Lymphocytic, Acute, L2;Leukemic Cell;Liver;Luciferases;Malignant Childhood Neoplasm;Manuscripts;Measures;Methodology;Methods;MLL-rearranged leukemia;Modeling;Molecular;Monitor;Mus;Mutation;New Agents;novel;novel therapeutics;Organ;Outcome;Outcomes Research;patient derived xenograft model;Patients;Performance;peripheral blood;Ph+ ALL;Pharmaceutical Preparations;Pharmacodynamics;Pharmacotherapy;Philadelphia Chromosome;Play;pre-clinical;Preclinical Testing;Preparation;programs;PTPRC gene;public-private partnership;Publications;Quality Control;Quality of life;Relapse;Reproducibility;Research;Research Personnel;Resources;response;Role;Schedule;skills;SNP genotyping;Spleen;standard of care;Statutes and Laws;Systemic disease;T-Lymphocyte;Tail;Testing;Time;Toxic effect;transcriptome sequencing;Transplantation;treatment response;United States National Institutes of Health;Variant;Veins

PROJECT_TITLE: NCI Pediatric In Vivo Testing Program - Leukemia


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Cardiovascular;Heart Disease;Lung

ORG_CITY: BIRMINGHAM

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative: Chlorine and bromine (Cl2 and Br2) are highly reactive and extremely toxic halogen gases that cause debilitating cardiopulmonary injury and death and effective therapies against such injuries are urgently needed. Our studies have provided confirmation of molecular targets for therapeutic development, proof of in vitro activity and in vivo proof-of-concept efficacy data for calpain inhibition based lead compound. These studies will allow calpain inhibitors or its analog to move forward and help design the pivotal safety and efficacy studies needed for regulatory FDA approval under the animal rule.

PI_NAMEs: AHMAD, SHAMA  (contact)

PROGRAM_OFFICER_NAME: NADADUR, SRIKANTH

PROJECT_TERMS: Acute;Adsorption;analog;Animal Model;animal rule;Animals;Antidotes;Authoritarianism;Biological;Biological Assay;Biological Availability;Biological Markers;Blood Cells;Blood Pressure;Brain;Bromine;Ca(2+)-Transporting ATPase;Calcium;Calpain;calpain inhibitor;Cardiac;Cardiac Output;Cardiopulmonary;Cardiovascular system;Cells;Cessation of life;chemical threat;Chemicals;Chlorine;Clinical;Clinical Chemistry;Complete Blood Count;Cytoskeleton;Data;design;Development;Dose;Drug Design;Drug Kinetics;effective therapy;efficacy evaluation;efficacy study;Endoplasmic Reticulum;Epithelium;Evaluation;Excretory function;Exposure to;Formulation;Funding;Gases;Goals;Half-Life;Halogens;Heart;heart function;Heart Hypertrophy;Heart Injuries;heart preservation;Heart Rate;hemodynamics;Hepatocyte;improved;In Vitro;in vitro activity;in vivo;Individual;Industrialization;Inhalation;Injury;Intramuscular;intraperitoneal;Kidney;kidney cell;Lead;lead optimization;Liver;Lung;lung histology;lung injury;Maximum Tolerated Dose;Mediating;Metabolism;meter;Modeling;Molecular Target;molecular targeted therapies;Morbidity - disease rate;mortality;Muscle Cells;Myocardial;Myocardium;novel;novel lead compound;Oral;Oryctolagus cuniculus;Oxygen;Paramedical Personnel;Parents;Peptide Hydrolases;Pharmaceutical Chemistry;Pharmaceutical Preparations;Physiologic intraventricular pressure;Plasma;programs;Property;Proteolysis;Publishing;Pulmonary Edema;Rattus;Research;respiratory;response;Route;Safety;safety study;Site;Soldier;Solubility;Spleen;Structure;Structure-Activity Relationship;subcutaneous;Survivors;Testing;Therapeutic;Therapeutic Agents;therapeutic development;therapeutic lead compound;therapeutically effective;Tissues;Toxic effect;United States National Institutes of Health;Validation;Vendor;weapons;World War I

PROJECT_TITLE: Novel lead compound advancement for mitigating halogen-induced mortality and morbidity.

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


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Immunotherapy;Skin Cancer

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: We will carry out analyses of tumor, serum and peripheral blood cells to comprehensively assess biomarkers of efficacy and toxicity in a phase II trial of combination checkpoint blockade with ipilimumab and nivolumab and the IL-6 receptor blocking antibody tocilizumab. Mass spectrometry and Luminex assessments will be carried out using serum samples at baseline and on treatment. Tumor and peripheral blood samples at baseline and on treatment will be analyzed using high resolution multi-parameter flow cytometry, single cell RNA seq and immunohistochemistry to comprehensively characterize and identify immune cell populations and RNA expression signatures associated with efficacy and toxicity.

PI_NAMEs: MEHNERT, JANICE M. (contact)

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: Acute-Phase Proteins;Aftercare;anti-PD1 antibodies;Antigen-Presenting Cells;Biological Assay;Biological Markers;Biological Response Modifiers;Blocking Antibodies;Blood Cells;Blood specimen;C-reactive protein;Cell Physiology;Cells;Charge;checkpoint inhibition;chemotherapy;clinical efficacy;Combination immunotherapy;Consult;cytokine;Data;Dendritic Cells;design;Dose;Evaluation;Flow Cytometry;Gene Expression Profile;Genetic Transcription;Immune;immune checkpoint blockade;immune-related adverse events;Immunohistochemistry;Immunosuppression;Immunotherapy;improved;insight;Institutional Review Boards;Interleukin 6 Receptor;Interleukin-6;ipilimumab;Liver;Macrophage;MALDI-TOF Mass Spectrometry;Mass Spectrum Analysis;Melanoma;Melanoma patient;Metastatic Melanoma;Nivolumab;Outcome;Patients;peripheral blood;Peripheral Blood Mononuclear Cell;phase 2 study;phase II trial;Phenotype;Population;primary endpoint;prognostic;programmed cell death ligand 1;Proteins;Resistance;Resolution;response;Role;Sampling;Serum;single-cell RNA sequencing;T-Lymphocyte;therapy resistant;tocilizumab;Toxic effect;transcriptome sequencing;trial design;tumor;Tumor Markers

PROJECT_TITLE: Correlative biomarkers of IL-6 blockade combined with checkpoint inhibition

STUDY_SECTION: CBSS

STUDY_SECTION_NAME: Cancer Biomarkers Study Section[CBSS]


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: ROOTSTOWN

ORG_DEPT: PHARMACOLOGY

ORG_NAME: NORTHEAST OHIO MEDICAL UNIVERSITY

ORG_STATE: OH

PHR: PUBLIC HEALTH RELEVANCE The proposed research is relevant to public health because the identification of specific gene- environment interactions that cause neurodegeneration are expected to reveal pathological mechanisms that will lead to early detection and the development of disease-modifying interventions for patients. The proposed research is relevant to the part of the NIH's mission that is directed at developing knowledge that will help reduce the burdens of human disability.

PI_NAMEs: FLEMING, SHEILA  (contact)

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: Acceleration;Affect;Age;Age Months;age related;age related neurodegeneration;Aging;alpha synuclein;Area;ATP phosphohydrolase;Basal Ganglia;Behavior;Behavioral;behavioral impairment;Bioenergetics;Biogenesis;Biological Assay;Brain;Brain region;Candidate Disease Gene;Cerebellum;Classification;cohort;Corpus striatum structure;Data;Defect;Development;disability;Disease;Early Diagnosis;Early identification;early onset;Early treatment;Economics;Elderly;Environment;Environmental Exposure;Environmental Risk Factor;Financial Hardship;Functional disorder;gene environment interaction;Genes;Genetic;Genetic Polymorphism;Genetic Predisposition to Disease;genetic risk factor;Hallervorden-Spatz Syndrome;Health;Heavy Metals;Hereditary Spastic Paraplegia;Heterozygote;Homeostasis;Human;In Vitro;in vivo;Inherited;Intervention;Iron;Knockout Mice;Knowledge;Lewy Bodies;Link;link protein;loss of function;loss of function mutation;LRRK2 gene;Maintenance;Manganese;Manganism;Measures;Metal exposure;Midbrain structure;Mission;Mitochondria;mitochondrial dysfunction;Mus;mutant;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Neuronal Ceroid-Lipofuscinosis;Neurons;neurotoxic;neurotoxicity;nigrostriatal degeneration;novel;Onset of illness;overexpression;PARK8 gene;PARK9 gene;Parkinson Disease;Pathologic;Pathology;Patients;Persons;Physiological;Population;Predisposition;Prevention;Prevention strategy;protein degradation;Proteins;Proteomics;Public Health;public health relevance;Quality Control;Quality of life;Regimen;repaired;Research;response;Risk;Risk Factors;Role;Syndrome;synucleinopathy;Techniques;Testing;therapeutic target;therapeutically effective;Toxic effect;translational potential;treatment strategy;United States National Institutes of Health;Variant;Work;Zinc

PROJECT_TITLE: ATP13A2 and Susceptibility to Neurodegeneration

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Clinical Research;Health Services;Lung;Patient Safety;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Survival from respiratory failure varies widely across hospitals, suggesting that improvements to the organization and delivery of care to respiratory failure patients may prevent deaths. Yet, recent changes affecting inpatient care have encouraged fragmentation—care that is spread out across multiple physicians during a hospitalization. The overarching goal of this proposal is to understand the impact of fragmented care on adults hospitalized with respiratory failure while identifying specific targets for protecting patients exposed to fragmented care from harm.

PI_NAMEs: ADMON, ANDREW JOHN (contact)

PROGRAM_OFFICER_NAME: KALANTARI, ROYA

PROJECT_TERMS: Acute respiratory failure;Address;Adult;Affect;Ambulatory Care;Award;Awareness;care delivery;care fragmentation;career;career development;Caring;Cessation of life;Characteristics;Clams;Clinical;Clinical Data;clinical effect;Clinical Investigator;Communication;Complex;Critical Care;Data;Data Sources;design;Development;Development Plans;Doctor of Philosophy;Ensure;Epidemiology;Event;evidence base;Excess Mortality;experience;Exposure to;Foundations;Global Change;Goals;Health Care Research;Healthcare Systems;Hospitalization;Hospitals;improved;innovation;inpatient service;Inpatients;instrument;Intensive Care Units;lecturer;Length of Stay;Link;Lung;Manuscripts;Measures;Medicine;Mentors;Methods;Michigan;Modernization;National Heart, Lung, and Blood Institute;National Research Service Awards;Nosocomial Infections;novel;Observational Study;Outcome;Outpatients;Patients;Pharmaceutical Preparations;Physicians;prevent;Public Health;Publications;Research;Research Methodology;Research Personnel;Respiratory Failure;Safety;Series;skills;Survey Methodology;Surveys;Techniques;Testing;thrombotic complications;Training;United States;Universities;Veterans Health Administration;Work

PROJECT_TITLE: Characterizing the Impact of Fragmented Care in Acute Respiratory Failure

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(MA)]


PHR: The primary risk factors for skin cancer development are sun exposure, age and an immunocompromised status. We propose that these risk factors are linked by their ability to promote the development, persistence and expansion of a senescent field that promotes overlying tumorigenesis. We will also determine whether transforming growth factor β production plays a central role in senescent field development, persistence and expansion. If successful, these studies will validate a novel two-field hypothesis for skin cancer development and provide evidence that anti-aging therapies may prove highly useful in suppressing skin cancer risk in individuals, particularly the immunosuppressed.

PI_NAMEs: KONGER, RAYMOND L (contact)

PROJECT_TERMS: Age;angiogenesis;anti aging;Area;cancer risk;carcinogenesis;Carcinoma;Cells;Characteristics;chemokine;Clonal Expansion;Cyclosporine;cytokine;Dermal;Development;differential expression;Epithelium;Exposure to;Fibroblasts;Ganciclovir;Graft Rejection;Hemoglobin;high risk;Image;Immune;Immune system;Immunocompromised Host;immunoregulation;immunosuppressed;Immunosuppression;Immunosuppressive Agents;in vivo;Individual;Inflammatory;Isogenic transplantation;Link;Malignant Conversion;Malignant Neoplasms;Maps;Measures;Mediating;Mediator;Mitotic;Modeling;Mus;mutant;Mutation;neoantigens;novel;organ transplant recipient;Paracrine Communication;Phenotype;Play;postmitotic;Process;Production;promoter;Risk;Risk Factors;Role;senescence;senescence associated secretory phenotype;senescent cell;senolytics;Signal Transduction;single-cell RNA sequencing;Sirolimus;Site;Skin Cancer;Skin Carcinogenesis;Solid;Stromal Cells;Sun Exposure;Sunlight;Testing;Therapeutic immunosuppression;Thymidine Kinase;Time;Training;transcriptome sequencing;Transforming Growth Factor beta;Transforming Growth Factor beta Receptors;Transplantation;tumor;tumorigenesis;Ultraviolet Rays;Ultraviolet Therapy;UV carcinogenesis;UV induced;UV Radiation Exposure;UVA induced;Variant;Veterans;Visualization;Wild Type Mouse

PROJECT_TITLE: Promotion of photocarcinogenesis by the senescent field and mechanisms for field persistence


ORG_CITY: NEW ORLEANS

ORG_NAME: SOUTHEAST LOUISIANA VETERANS HEALTH CARE

ORG_STATE: LA

PHR: Project Narrative Alcohol consumption is classified as a human carcinogen by the International Agency for Research on Cancer (IARC; 2010,2012). Nearly 75% of the US population consumes alcohol, including veterans and civilians, of which 7% become alcoholic. Heavy alcohol consumption constitutes a significant social problem and has been identified as a risk factor for pancreatic cancer, however, the possible impact and molecular mechanism of alcohol in the initiation, progression and metastasis of pancreatic cancer is unknown. Therefore, the main goal of this application is to examine the biological role of alcohol toxicity in the induction of pancreatic cancer and to identify genes mediating alcohol induced cellular transformation and progression of pancreatic cancer.

PI_NAMEs: SHANKAR, SHARMILA  (contact)

PROJECT_TERMS: Acetaldehyde;Address;Alcohol consumption;alcohol effect;alcohol exposure;alcohol use disorder;Alcohols;aldehyde dehydrogenases;Analysis of Variance;animal imaging;Attenuated;BALB/c Nude Mouse;Binding;Biochemical;Biological;Biological Process;Biology;Blood;Cancer cell line;cancer initiation;cancer risk;cancer stem cell;Carcinogens;Cell Survival;cell transformation;Cells;chemotherapy;ChIP-seq;Chronic;Classification;comparison group;Complex;CRISPR/Cas technology;CYP2E1 gene;cytokine;Data;Development;diagnostic biomarker;Disease;disease prognosis;Ductal Epithelial Cell;Early Diagnosis;Epithelial Cells;Ethanol;Ethanol toxicity;Etiology;Face;Future;Gene Expression;Genes;Genetic Transcription;glutathione peroxidase;Glutathione S-Transferase;Goals;Growth;Histologic;Homeobox;Human;IL8 gene;Implant;improved;In Vitro;in vivo;Inflammation;Inflammatory;inflammatory milieu;Interleukin-1 beta;Interleukin-6;International Agency for Research on Cancer;knock-down;Knockout Mice;Knowledge;KRASG12D;Liver;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Measures;Mediating;metaplastic cell transformation;military veteran;Molecular;Monitor;mouse model;Mus;Neoplasm Metastasis;notch protein;novel;novel strategies;Oncogenic;overexpression;Pancreas;Pancreatic duct;pancreatic tumorigenesis;Pathway interactions;Pattern;PET/CT scan;pluripotency;Population;problem drinker;Production;Quantitative Reverse Transcriptase PCR;Radiation therapy;Recurrence;Regulation;Risk;Risk Factors;Role;self-renewal;Social Problems;spheroids;stem cell biomarkers;stem cells;stemness;Survival Rate;Techniques;Testing;Time;Tissues;TNF gene;transcription factor;transcriptome;transcriptome sequencing;Transgenic Mice;Transgenic Organisms;tumor;tumor growth;tumorigenic;Veterans;Vulnerable Populations;Western Blotting;X-Ray Computed Tomography

PROJECT_TITLE: Role of Alcohol as a risk factor in the induction of Pancreatic Carcinogenesis


ORG_CITY: IOWA CITY

ORG_NAME: IOWA CITY VA MEDICAL CENTER

ORG_STATE: IA

PHR: The proposed research will identify two mechanisms activating TAZ and YAP in sarcomas and we anticipate other cancers as well. The research is relevant to Veteran health since sarcomas are more common in elderly patients as well as those with certain occupational exposure including herbicides affecting the Veteran population (e.g. Agent Orange). However TAZ and YAP are not only activated in sarcomas, but also breast, colon, liver, lung, pancreas, and thyroid cancers. This proposal utilizes sarcomas not only to understand TAZ/YAP dysregulation in sarcomas, but also as a model system to understand TAZ/YAP activation in other cancers which are common within the Veteran population. We anticipate this approach will provide the basis for combinatorial therapy targeting the PI3K-TAZ/YAP and Hippo-TAZ/YAP axes and provide additional therapeutic options to Veteran patients, thus lengthening life and reducing illness for these patients.

PI_NAMEs: TANAS, MUNIR  (contact)

PROJECT_TERMS: Address;Affect;agent orange;Amputation;Anatomy;Bioinformatics;Biological Assay;Biological Models;Bone Tissue;Cell Cycle;Cell Line;Childhood Rhabdomyosarcoma;Clinic;Clinical;Clinical Data;clinically relevant;Colon Carcinoma;combinatorial;Combined Modality Therapy;Coupled;Data;differential expression;Enhancers;Event;Gene Deletion;Gene Expression Profile;Gene Expression Profiling;Genes;Genetic Engineering;Genetic Transcription;Genetically Engineered Mouse;Genomics;Goals;Health;Herbicides;Histologic;Histone Deacetylase Inhibitor;Histone Deacetylation;In Vitro;in vitro testing;in vivo;Incidence;Individual;innovation;Intramuscular;Knock-out;Knowledge;LATS1 gene;Lead;Life;Limb Salvage;Luciferases;Malignant Breast Neoplasm;Malignant Fibrous Histiocytoma;Malignant neoplasm of liver;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant neoplasm of thyroid;Malignant Neoplasms;MAP4;Mediating;Medical;military veteran;Modeling;mouse model;Mus;Muscle;Neoplasm Metastasis;new therapeutic target;novel;novel therapeutic intervention;Nucleic Acid Regulatory Sequences;Occupational Exposure;older patient;Oncogenes;Oncogenic;Oncoproteins;Outcome;Pathway interactions;Patients;pharmacologic;Pharmacology Study;Phosphorylation;Phosphotransferases;PIK3CG gene;Play;Proliferating;promoter;protein expression;Protein-Serine-Threonine Kinases;Publishing;Quantitative Reverse Transcriptase PCR;reconstitution;Regulation;Reporter;Research;response;Rhabdomyosarcoma;Role;Salvage Therapy;Sampling;Sarcoma;Serine;Signal Pathway;Signal Transduction;soft tissue;targeted treatment;Testing;Therapeutic;therapeutic target;Time;Transcription Coactivator;transcriptome;transcriptome sequencing;tumor;tumor progression;Veterans;Virus;Work;Xenograft procedure

PROJECT_TITLE: Upstream regulation of TAZ and YAP in sarcomas: Towards combinatorial therapytargeting the Hippo pathway


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Data Science;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Narrative Multi-site neuroimaging studies suffer from significant inter-scanner variabilities that are larger than the effect sizes observed in many brain disorders. In this grant, we propose to develop and disseminate MRI sequences that are vendor-neutral and can be implemented in the same manner across scanners. Our work also involves developing a unified image reconstruction framework and new algorithms to harmonize any remaining differences in the data due to disparate scanner hardware configurations, which will significantly increase reproducibility in multi-site neuroimaging studies.

PI_NAMEs: BILGIC, BERKIN ;RATHI, YOGESH  (contact)

PROGRAM_OFFICER_NAME: BARRY, ROBERT LEO II

PROJECT_TERMS: 3-Dimensional;Acceleration;Address;Adoption;Algorithms;Anisotropy;Attenuated;Brain;Brain Diseases;Brain region;Calibration;Code;Coronavirus;Data;data acquisition;data harmonization;deep learning;density;Detection;Development;Diffusion Magnetic Resonance Imaging;Disease;Disparate;Echo-Planar Imaging;Environment;Functional Magnetic Resonance Imaging;Goals;Grant;gray matter;Health;human subject;Image;image reconstruction;improved;in vivo;Knowledge;Laboratory Research;Learning;Liquid substance;Magnetic Resonance Imaging;Maps;Measures;Mental disorders;Neurobiology;neuroimaging;neuropsychiatric disorder;novel;open source;Pathology;Performance;Physiologic pulse;Predisposition;Protocols documentation;Protons;quantitative imaging;radio frequency;radiologist;Recommendation;reconstruction;Recovery;Relaxation;Reproducibility;Research;research study;Resolution;Sample Size;Scanning;Scheme;Schizophrenia;Shapes;simulation;Site;Slice;Source;System;Techniques;Technology;Time;Tissues;Translational Repression;Translations;transmission process;Travel;Variant;Vendor;white matter;Work

PROJECT_TITLE: Harmonizing data acquisition, reconstruction, and analysis for reproducible, cross-vendor, open source MRI

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ORG_CITY: BALTIMORE

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: Triple-negative breast cancer (TNBC) is a major cause of death among breast cancer patients; and is the only subtype of breast cancer that is still lacking effective chemoprevention and therapeutic options. TNBC subtype has the highest level of both IL-6 and CDK4/6 pathways’ co-activation compared to other breast cancer subtypes; and TNBC patients with high IL-6 and CDK4/6 pathways’ co-activation in their tumors are associated with a shortened time to metastasis development. The development of drugs that co-target IL-6 and CDK4/6 pathways for TNBC preventive therapy is highly desirable and should have a high impact for women Veteran’s health. We propose to evaluate the efficacy of bazedoxifene and abemaciclib combination in suppressing TNBC tumor growth and preventing tumor recurrence and metastasis in complementary mouse orthotopic tumor and metastatic models in vivo. Our long-term goal is to co-target IL-6 and CDK4/6 pathways as a novel approach of cancer preventive therapy for TNBC using two FDA-approved drugs bazedoxifene and abemaciclib.

PI_NAMEs: LIN, JIAYUH  (contact)

PROJECT_TERMS: advanced disease;Affect;Antineoplastic Agents;Area;Aromatase Inhibitors;Biological Availability;bone;Brain;Breast Cancer Cell;Breast Cancer cell line;breast cancer metastasis;Breast Cancer Patient;breast cancer progression;Breast Cancer Risk Factor;cancer cell;cancer chemoprevention;cancer subtypes;Cause of Death;CDK4 gene;Cell secretion;Cell Survival;Chemoprevention;Clinical;Clinical Trials;clinically relevant;Complex;Conjugated Estrogens;Data;Development;Distant;Drug Combinations;drug development;Drug Targeting;efficacy evaluation;Epidermal Growth Factor Receptor;Estrogen receptor negative;Estrogen receptor positive;Excision;Experimental Models;FDA approved;Goals;Growth;Health;hormone receptor-positive;Human;IL-6 inhibitor;IL6ST gene;Immunocompetent;improved;In Vitro;in vivo;in vivo Model;inhibitor;Injections;Interleukin Activation;Interleukin-6;intravenous injection;Literature;Liver;Lung;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Marketing;Measures;Medical;Metastatic breast cancer;Metastatic malignant neoplasm to brain;Metastatic Neoplasm to the Bone;Metastatic Neoplasm to the Liver;Metastatic Neoplasm to the Lung;Military Personnel;Modeling;mortality;mouse model;Mus;Names;Neoplasm Circulating Cells;Neoplasm Metastasis;novel;novel marker;novel strategies;Oral;Organ;orthotopic breast cancer;Outcome;Pathway interactions;Patient Care;Patient-derived xenograft models of breast cancer;Pharmaceutical Preparations;pharmacologic;Play;Postmenopausal Osteoporosis;preclinical study;predictive marker;prevent;Prevention;Prevention approach;Preventive;Preventive therapy;Primary Neoplasm;Prognosis;recruit;Recurrent tumor;Reporting;research clinical testing;Research Project Grants;Resistance;resistance mechanism;Role;Safety;Sampling;Selective Estrogen Receptor Modulators;Signal Transduction;Site;small molecule;small molecule inhibitor;STAT3 gene;Tail;Testing;Therapeutic;Time;Translating;triple-negative invasive breast carcinoma;tumor;tumor growth;tumor progression;Veins;Veterans;Woman

PROJECT_TITLE: Co-Targeting IL-6 and CDK4/6 Pathways as a Novel Approach of Preventive Therapy for Triple-Negative Breast Cancer


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

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: For African-American women, breast cancer mortality is higher than any other race/ethnicity, in spite of having lower incidence rates. In breast cancer, collagen re-alignment is a primary part of the disease and is predictive of risk, subtype, outcome and recurrence with limited data on contribution to racial disparities. Our study proposes to define protein modifications linked to ancestry-dependent collagen realignment within the tumor microenvironment which could lead to more accurate treatments that eliminate racial disparities in breast cancer.

PI_NAMEs: ANGEL, PEGGI M (contact)

PROGRAM_OFFICER_NAME: WOODHOUSE, ELIZABETH

PROJECT_TERMS: Affect;African American;African American Women;Alcohols;American;Automobile Driving;Breast;Breast Cancer Early Detection;breast cancer metastasis;Breast Cancer Prevention;breast cancer progression;Breast Cancer Risk Factor;breast density;breast lumpectomy;cancer type;Cells;clinically relevant;COL1A2 gene;Collagen;Collagen Fiber;Companions;Contraceptive Usage;Data;Data Reporting;density;Deposition;diagnostic signature;Disease;Drug resistance;early detection biomarkers;Environment;Ethnic Origin;European;Extracellular Matrix;Generations;Human;Hydroxylation;immune cell infiltrate;Incidence;Invaded;Knowledge;Link;Macrophage;Malignant Breast Neoplasm;Mammary Gland Parenchyma;Mammary Neoplasms;Maps;Marital Status;Measurement;Measures;Microscopy;migration;Minority Groups;Modification;mortality;Neoplasm Metastasis;new technology;novel;Oncogenic;Outcome;Peptides;Post-Translational Protein Processing;Post-Translational Regulation;prevent;prognostic signature;Proliferating;Proline;Proteomics;Race;racial disparity;receptor;Recurrence;Regulation;Risk Factors;risk prediction;Role;second harmonic;Signal Transduction;Site;Smoking;Socioeconomic Status;socioeconomics;Stratification;Structure;technology platform;Testing;The Cancer Genome Atlas;Time;Tissue Banks;Tissue imaging;Tissue Microarray;Tissues;triple helix;triple-negative invasive breast carcinoma;tumor;tumor microenvironment;tumor progression;tumorigenic;type I collagen alpha 1;Variant;Woman

PROJECT_TITLE: Collagen Sequence Variants in Racial Disparities of Breast Cancer

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Chronic Pain;Headaches;Migraine;Neurosciences;Pain Research;Prevention

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Narrative Many patients do not receive sufficient relief with currently available therapies. We propose to investigate brain circuits of migraine pain that may ultimately lead to development of improved therapies.

PI_NAMEs: NAVRATILOVA, EDITA ;NEUGEBAUER, VOLKER ;PORRECA, FRANK  (contact)

PROGRAM_OFFICER_NAME: OSHINSKY, MICHAEL L

PROJECT_TERMS: Acute;Address;Affect;Affective;Agonist;Agreement;allodynia;Amygdaloid structure;antagonist;Antibodies;Antibody Therapy;Area;Behavior;behavioral outcome;behavioral response;Bilateral;Blood - brain barrier anatomy;Brain;Brain region;Calcitonin Gene-Related Peptide;Calcitonin-Gene Related Peptide Receptor;Calcium;Cell Nucleus;cell type;Cells;Cephalic;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;coping;cranium;CRISPR/Cas technology;Data;Development;Disease;Dorsal;Dura Mater;Electrophysiology (science);Emotional;experience;Fc Receptor;Female;Fiber;Fright;Functional disorder;Genetic;genetic manipulation;Glutamates;Human;human imaging;Ibotenic Acid;Image;imaging study;improved;Inflammation Mediators;Knowledge;Lesion;Link;male;Measures;Mediating;Meningeal;Meninges;Methods;Microscopy;Migraine;migraine treatment;Modeling;Mus;Nervous System Disorder;neural;neuroimaging;Neurons;Nociception;Nociceptors;optogenetics;Organism;Output;Pain;pain behavior;parabrachial nucleus;Pathology;Pathway interactions;Patients;Peptides;Peripheral;Persons;Pharmaceutical Preparations;pharmacologic;Phase;Pontine structure;pre-clinical;preclinical study;prevent;Preventive;Preventive treatment;Quality of life;redshift;response;Role;sensory input;Severities;Signal Transduction;Site;Slice;small molecule;Structure;Synapses;therapy development;transmission process;Trigeminal Pain;Trigeminal System;Visceral

PROJECT_TITLE: Brain Circuits of Migraine Pain

STUDY_SECTION: NPI

STUDY_SECTION_NAME: Neurobiology of Pain and Itch Study Section [NPI]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Vaccines;Dissemination and Implementation Research;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Immunization;Infectious Diseases;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Vaccine Related

ORG_CITY: SAN DIEGO

ORG_NAME: SAN DIEGO STATE UNIVERSITY

PHR: Project Narrative COVID-19 has disproportionately impacted Latinos and other racial/ethnic minority groups. Effective intervention strategies are needed to stop household- and subsequent community- spread of COVID-19 among Latinos. This study will test the immediate and short-term effectiveness of a multilevel intervention to increase the uptake of COVID-19 vaccines among Latinos.

PI_NAMEs: CRESPO, NOE CUAUHTEMOC (contact);RAMERS, CHRISTIAN B

PROGRAM_OFFICER_NAME: DAGHER, RADA K

PROJECT_TERMS: acceptability and feasibility;Address;Affect;arm;behavior change;Behavior Therapy;Behavioral;behavioral health;California;Catchment Area;Cessation of life;Chronic Disease;Clinic;Clinical;clinical practice;Cluster randomized trial;cohort;Collaborations;Communication;Communities;community academic partnership;Community Health Aides;community intervention;community partners;community transmission;County;COVID-19;COVID-19 monitoring;COVID-19 mortality;COVID-19 patient;COVID-19 risk;COVID-19 vaccination;COVID-19 vaccine;Death Rate;Disparity;distrust;economic impact;Education;effective intervention;Effectiveness;effectiveness evaluation;Effectiveness of Interventions;effectiveness testing;Environment;ethnic minority population;experience;Family health status;FDA Emergency Use Authorization;Federally Qualified Health Center;flexibility;Future;Government;group intervention;Health;Health behavior;health care service;Health Educators;high risk population;Home;Household;implementation evaluation;implementation fidelity;implementation outcomes;implementation process;improved;infection rate;Infrastructure;innovation;Intervention;Latin America;Latino;Latino Population;Low income;Mental Health;Minority-Serving Institution;Misinformation;model design;Modeling;Morbidity - disease rate;Neighborhoods;novel;Occupations;Outcome;pandemic disease;patient outreach;Patients;physical conditioning;Population;Positioning Attribute;Poverty;Primary Care Physician;Program Acceptability;psychosocial;Public Health;Quality of life;racial minority population;Randomized;Research;Resistance;Risk;SARS-CoV-2 infection;secondary outcome;Single-Blind Study;Subgroup;Sustainable Development;System;Target Populations;Testing;Time;Trust;Underserved Population;United States;United States Dept. of Health and Human Services;Universities;uptake;Vaccination;vaccine acceptance;Vaccines;Work

PROJECT_TITLE: Increasing COVID-19 Vaccine Uptake among Latinos through a Targeted Clinical and Community-behavioral Intervention

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-VH-G(90)S]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Human Genome;Lymphatic Research;Lymphoma;Racial and Ethnic Minority Health Research;Rare Diseases

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Project Relevance to Public Health: Inherited and acquired variants have been identified for Chronic Lymphocytic Leukemia (CLL) that predispose men and women to increased risk of CLL; however, all of the prior studies have been done in Caucasians. This application proposes to extend the genomic work in African American CLLs to evaluate genetic heterogeneity. These results will improve our understanding of the underlying biology of CLL risk and prognosis, and ultimately may reduce the health disparity that is observed between African American and Caucasian populations in CLL.

PI_NAMEs: BRAGGIO, ESTEBAN ;SLAGER, SUSAN L (contact)

PROGRAM_OFFICER_NAME: CAGA-ANAN, EMILIE CHARLISSE F

PROJECT_TERMS: African American;African American population;Age of Onset;anti-cancer research;Automobile Driving;B-Cell Neoplasm;Biological;Biology;Caucasians;Characteristics;Chromosomal Rearrangement;Chronic Lymphocytic Leukemia;Clinical;Collection;Data;deep sequencing;Development;Diagnosis;Disease;Disparity;DNA sequencing;epigenomics;Etiology;European;exome sequencing;experience;Frequencies;Gene Frequency;Genes;Genetic;Genetic Heterogeneity;genome sequencing;genome wide association study;Genomics;Genotype;Germ Lines;Goals;Heterogeneity;improved;Incidence;indexing;Individual;Inherited;insight;Knowledge;leukemia;leukemogenesis;Measures;men;Minority;Molecular;Morbidity - disease rate;mortality;multiple omics;Mutate;Mutation;novel;Outcome;Pathogenesis;Patients;polygenic risk score;Population;Predisposition;Privatization;Prognosis;prognostic;Prognostic Factor;prognostication;Public Health;Race;racial difference;racial population;Recurrence;Reduce health disparities;Research Design;Risk;risk stratification;Single Nucleotide Polymorphism;Somatic Mutation;Susceptibility Gene;targeted sequencing;Testing;Therapeutic Intervention;Time;transcriptome;transcriptomics;tumor;tumor DNA;tumor heterogeneity;Variant;whole genome;Woman;Work

PROJECT_TITLE: Germline and Somatic Genomic Studies in CLL Minorities

STUDY_SECTION: CHSA

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology A Study Section[CHSA]


NIH_SPENDING_CATS: American Indian or Alaska Native;Bioengineering;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hepatitis;Hepatitis - C;Infectious Diseases;Liver Disease;Racial and Ethnic Minority Health Research;Social Determinants of Health

PHR: PROJECT NARRATIVE Despite significant recent advances in the development of highly effective and affordable HCV treatment, one of the major challenges in HCV infection management is rapid and early diagnosis of active HCV infection particularly those in resource-limited settings and those disproportionately affected with HCV infection such as the American Indians and Alaska Natives (AI/AN). Low-cost, rapid, sensitive, and specific point of care HCV antigen testing is an attractive alternative approach to the time-consuming, expensive, and suboptimal two- step HCV testing process (HCV Ab testing followed by HCV RNA testing) that holds great promise for one-step HCV screening and diagnosis. The main goal of this interdisciplinary project is developing a smartphone-based diagnostic system for rapid (<30 minutes) and sensitive (LoD of 200 IU/mL to 1000 IL/mL) HCV detection using fingerprick volume (<100 µL) of a whole blood sample placed on an inexpensive (<$2 material cost), disposable, and mass-producible microfluidic-based cartridge.

PI_NAMEs: SHAFIEE, HADI  (contact)

PROGRAM_OFFICER_NAME: LASH, TIFFANI BAILEY

PROJECT_TERMS: Acute Hepatitis C;Affect;African American population;Alaska Native;Algorithms;American Indians;antigen test;Artificial Intelligence;Biological Assay;Blood specimen;Caring;Cellular Phone;Chemistry;Chronic Hepatitis C;Cirrhosis;Clinical;clinically relevant;Consumption;cost;Death Rate;design;Detection;Development;Development Plans;Devices;Diagnosis;Diagnostic;diagnostic platform;Diagnostic tests;Drops;Early Diagnosis;Ethnic Population;FDA approved;Fingers;follow-up;Gases;Generations;global health;Glycerol;Goals;HCV screening;health disparity;Hemodialysis;Hepatitis C;Hepatitis C Antibodies;Hepatitis C Therapy;Hepatitis C virus;Hydrogen Peroxide;Image;Immunocompromised Host;improved;Incidence;Individual;Infection;infection management;infection rate;interest;Label;Left;Machine Learning;Magnetism;microchip;Microfluidics;Molecular Conformation;Monitor;mortality;nanoparticle;nanoprobe;Native Americans;Not Hispanic or Latino;Pathogen detection;Patients;Persons;point of care;Primary carcinoma of the liver cells;Process;Publishing;racial population;rapid diagnosis;Resource-limited setting;Sampling;scale up;Serum;smartphone application;Surface;Telephone;Testing;Therapeutic immunosuppression;Time;viral detection;Viral Load result;viral RNA;Virus;virus testing;Water;Whole Blood;World Health Organization

PROJECT_TITLE: A smartphone-enabled point of care HCV Ag diagnostics to reduce HCV-related health disparities


ORG_CITY: College Station

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: TEXAS A&M AGRILIFE RESEARCH

ORG_STATE: TX

PHR: Project Narrative This project aims to reveal the mechanisms of how single-stranded RNA bacteriophages (ssRNA phages) PP7 and AP205 package their genomic RNA to be delivered to Pseudomonas aeruginosa and Acinetobacter spp., respectively via the Type IV pili, by combining high-resolution cryo-electron microscopy, in-situ fluorescence microscopy, and multi-scale computational modeling. Unlike double-stranded DNA phages, ssRNA phages do not have pressurized capsids or dedicated DNA delivery machinery, and how ssRNA phages package and deliver RNA into the cell remains a mystery. Knowledge gained from this project will provide an alternative strategy for treating multidrug-resistant bacterial infections by specifically cleaving/stalling Type IV pili.

PI_NAMEs: ZENG, LANYING ;ZHANG, JUNJIE  (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Acinetobacter;Adsorption;Affect;Antibiotic Resistance;Bacteria;Bacterial Infections;Bacterial Pili;Bacteriophages;Binding;Binding Proteins;Biology;Capsid;Capsid Proteins;cell preparation;Cells;Coliphages;Color;Complex;Cryo-electron tomography;Cryoelectron Microscopy;Cytosol;Data;Data Set;Dedications;DNA;DNA delivery;ds-DNA;Electroporation;Engineering;Enterobacteria phage MS2;Environment;Escherichia coli;experimental study;fluorescence imaging;Fluorescence Microscopy;Future;Genetic;Genetic Materials;genomic RNA;Goals;Gram-Negative Bacteria;Guidelines;Health Care Costs;Heat-Shock Response;Human;Image;In Situ;in situ imaging;Infection;insight;interest;kinetosome;Knowledge;Label;Life;Measures;member;Methods;Modeling;Molecular;Multi-Drug Resistance;multi-scale modeling;mutant;pathogen;pathogenic bacteria;Pathway interactions;Penetration;Pilum;plasmid DNA;Plasmids;Play;pressure;Process;Proteins;Pseudomonas;Pseudomonas aeruginosa;receptor;Regulation;Resistance;Resolution;RNA;RNA delivery;RNA Phages;Role;Site-Directed Mutagenesis;structural determinants;Structure;success;superresolution microscopy;Testing;time use;tool;Toxin;Virion;Virulence;Virulence Factors;Virus;Visualization;Work

PROJECT_TITLE: RNA penetrations into bacteria.

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


NIH_SPENDING_CATS: Natural Products

ORG_CITY: COLLEGE STATION

ORG_DEPT: CHEMISTRY

ORG_NAME: TEXAS A&M UNIVERSITY

PHR: PROJECT NARRATIVE It can be safely argued that nitrogen heterocycles exhibit biological profiles that are essential for the treatment of human disease. Inspired by the past 60 years of organolithium chemistry and the advances in transition metal catalysis, the development of asymmetric deprotonation cross-coupling sequences is proposed. The carbon- carbon bond forming possesses described seek to address the longstanding problem of direct asymmetric func- tionalization of remote C-H bonds in various alkaloids allowing their physiochemical properties to be easily tuned.

PI_NAMEs: THOMAS, ANDY ALEXANDER (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Lewis Base Ligands Designed to Control Carbon-Carbon Bond Formation


ORG_CITY: Aurora

ORG_NAME: VA EASTERN COLORADO HEALTH CARE SYSTEM

ORG_STATE: CO

PHR: Obesity is associated with increased risk of developing colorectal cancer, which is the third most commonly diagnosed cancer in the VA health care system. As of 2017, 78% of Veterans are overweight or obese. Factors secreted from adipose tissue, the largest endocrine organ, are altered during obesity. The proposed experiments will determine the role of adipose tissue-derived extracellular vesicles in the initiation and progression to colorectal cancer, a deadly cancer in the Veteran population.

PI_NAMEs: THEISS, ARIANNE L (contact)

PROJECT_TERMS: Adipocytes;Adipose tissue;Antitumor Response;Automobile Driving;base;beta catenin;Body mass index;Breast Cancer Model;cancer cell;cancer diagnosis;cell growth;Cell Survival;cell type;Cells;Colon;colon tumorigenesis;colonic crypt;Colorectal Cancer;colorectal cancer progression;combat;Communication;Consumption;Data;Distant;DNA Sequence Alteration;Endocrine Glands;Environment;Enzymes;Epithelium;Exhibits;exosome;experimental study;extracellular vesicles;Fatty acid glycerol esters;fatty acid metabolism;Fatty Acids;Fostering;Genetic Transcription;Goals;Growth;Healthcare Systems;Homeostasis;Human;inhibitor;Intake;intestinal epithelium;LGR5 gene;Lipids;Malignant Breast Neoplasm;Malignant Neoplasms;Measures;Mediating;Messenger RNA;Metabolism;MicroRNAs;military veteran;Mitochondria;mitochondrial metabolism;Mitochondrial Proteins;Molecular;mouse model;Mus;Non obese;Obese Mice;obese patients;obese person;Obesity;Oncoproteins;Organ;Organoids;Overweight;oxidation;Oxidative Phosphorylation;Pathway interactions;Patients;Phenotype;Production;progenitor;Proliferating;Proteins;receptor;Risk;Role;saturated fat;Signal Induction;Signal Pathway;Signal Transduction;src-Family Kinases;stem cell function;stem cells;stemness;subcutaneous;Surface;System;Testing;therapeutically effective;Transcriptional Activation;translational study;triple-negative invasive breast carcinoma;tumor;tumor progression;tumorigenesis;United States;Up-Regulation;uptake;vesicular release;Veterans;Veterans Health Administration;Visceral;western diet

PROJECT_TITLE: Adipose Tissue Extracellular Vesicles in Colorectal Tumorigenesis


PHR: The overall goal of the proposed research is to understand the factors that contribute to the development and progression of lung adenocarcinoma, a form of cancer that accounts for 40% of lung cancer cases, disproportionately affects veterans, increases with age, and is associated with tobacco smoke and deployment-related exposures. Given these demographics, armed services members and veterans represent an at-risk population for lung adenocarcinoma. Therefore, veterans and their families will benefit significantly from our improved understanding of lung adenocarcinoma progression and the development of new treatment strategies for a disease that presently has only a 20% five-year survival rate.

PI_NAMEs: EVANS, CHRISTOPHER M (contact)

PROJECT_TERMS: 3-Dimensional;Address;Adenocarcinoma Cell;Affect;Age;Amino Acids;Anabolism;animal imaging;Animals;Apoptosis;Apoptotic;Binding;Biological Assay;Biology;Breeding;Cancer Biology;cancer cell;Cancer Etiology;cell growth;Cell Line;Cell Nucleus;Cell Proliferation;Cells;Cellular biology;Cessation of life;Chemoresistance;Chronic Disease;coping;Data;demographics;Development;Dimerization;Disease;Distal;disulfide bond;effective therapy;Endoplasmic Reticulum;endoplasmic reticulum stress;Enzymes;Epithelial Cells;Epithelium;experience;Family;gene editing technology;Gene Expression;Gene Proteins;glycosylation;Goals;Growth;Health;Host Defense;Human;human tissue;Imaging Techniques;improved;In Vitro;in vivo;Individual;Induction of Apoptosis;Inhibition of Apoptosis;inhibitor;innovation;Inositol;Intervention;Invaded;Knockout Mice;KRAS2 gene;KRASG12D;Link;Lung;Lung Adenocarcinoma;lung carcinogenesis;Malignant neoplasm of lung;Malignant Neoplasms;Mammals;Measures;Mediating;Metabolism;Molecular;molecular imaging;mortality;mouse model;MUC5AC gene;MUC5B gene;Mucinous;Mucins;Mucous body substance;Mucous Membrane;Mus;Mutation;neoplastic cell;novel;novel therapeutic intervention;Oncogenic;overexpression;Pathogenesis;Patients;pharmacologic;Polymers;Populations at Risk;Positioning Attribute;Proliferating;Protein Isoforms;proteostasis;proteostasis loss;Recurrence;Research;Risk;Sampling;sensor;service member;Severities;Signal Pathway;Signal Transduction;Signaling Protein;sugar;Survival Rate;System;Testing;Tissue imaging;Tobacco smoke;Transgenic Mice;Transgenic Model;Translations;tumor;Tumor Burden;Tumor Promotion;tumorigenesis;Urethane;Vascularization;Veterans;Xenograft procedure

PROJECT_TITLE: Effects of Polymeric Mucin Expression on Lung Carcinogenesis


ORG_CITY: NASHVILLE

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: TN

PHR: Despite great progress in treating primary tumors, metastatic disease remains incurable. Veterans with cancer tend to have poorer survival statistics, more metastatic disease, and more complications. The recent rapid development of immunotherapies has shown some promise, but the current approaches have not been successful in bone metastatic disease. In this application, we will investigate potential approaches to reduce tumor recruitment of pro-tumor macrophages (M2) or induce anti-tumor (M1) responses. These studies will improve our understanding of tumor- bone marrow immune interactions to build therapeutic approaches for reducing bone metastatic breast cancer. Outcomes from these studies may also help inform therapeutic strategies for other bone metastatic tumors seen frequently in the VA (prostate, lung, etc)

PI_NAMEs: RHOADES (STERLING), JULIE A (contact)

PROJECT_TERMS: Address;animal imaging;anti-tumor immune response;arginase;bone;Bone Diseases;Bone Marrow;Bone Marrow Neoplasms;Breast Cancer Cell;Breast Cancer Model;Breast Cancer Patient;Cancer Etiology;Cell Cycle;Cell Proliferation;Cells;Cessation of life;chemokine receptor;Clinical Research;Complex;curative treatments;cytokine;Data;Development;Differentiation Antigens;Disease;efficacy evaluation;Environment;ex vivo imaging;experience;Flow Cytometry;fluorescence imaging;Fracture;Gene Modified;Genetic;Genetic Transcription;Growth Factor;high risk;Histology;Homeostasis;Immune;Immune response;Immunocompetent;Immunologic Stimulation;Immunologic Surveillance;Immunotherapy;improved;improved outcome;inhibitor;innovation;Interleukin-4;Interleukins;ITGAM gene;knock-down;Knockout Mice;Laboratories;Ligands;Localized Disease;Lung;Macrophage;Macrophage Activation;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Measures;Mediating;Metastatic breast cancer;Metastatic Neoplasm to the Bone;microCT;Modeling;Monitor;Morbidity - disease rate;mouse model;Multidrug Resistance Gene;Mus;Myelogenous;Myeloid Progenitor Cells;Neoplasm Metastasis;neoplastic cell;NF-kappa B;Organ;Osteoblasts;Osteoclasts;Outcome Study;overexpression;Paclitaxel;Pain;parathyroid hormone-related protein;Patient-Focused Outcomes;Patients;Phagocytes;pharmacologic;Phenotype;Physiologic calcification;Population;Population Heterogeneity;pre-clinical;Pre-Clinical Model;precursor cell;Primary Neoplasm;Production;programs;Prostate;Proteins;receptor;recruit;Regulation;Research;response;Roentgen Rays;Role;Signal Pathway;Signal Transduction;Site;Skeleton;standard of care;statistics;stem cell differentiation;stem cell population;Surface;Testing;Therapeutic;therapy development;TNF gene;Toxic effect;transcription factor;tumor;Tumor Burden;Tumor Expansion;tumor growth;tumor microenvironment;Tumor Promotion;Tumor-associated macrophages;tumor-immune system interactions;Veterans;Woman;Women's mortality;Work;Zoledronic Acid

PROJECT_TITLE: Reprogramming tumor associated macrophages to induce anti-tumor immune responses in bone metastatic breast cancer.


PHR: Narrative: Prostate cancer (PCa) is the second leading cause of cancer deaths among men in the USA. PCa metastases and emergence of castrate-resistant PCa (CRPC) contribute to overall poor survival; underlying the urgent, yet unmet, need for identification and characterization of new targets for intervention in lethal prostate cancer. Our goal is to address this vital knowledge gap by characterizing the role of Prostate Derived Ets Transcription Factor (PDEF) in PCa aggressiveness, thereby reducing the prostate cancer-related death. We propose mechanistic experiments that may pave way for development of new therapy against therapy resistance on PCa. These studies highly relevant to the mission of VA BLRD and is likely to have a significant impact on saving lives of veterans by providing new and novel targets for intervention against prostate cancer in the immediate future.

PI_NAMEs: KOUL, HARI K (contact)

PROJECT_TERMS: Address;androgen deprivation therapy;androgen independent prostate cancer;Androgens;Binding Sites;Cancer Etiology;Cancer Patient;Cell Line;Cell Migration Inhibition function;cell motility;Cells;Cessation of life;ChIP-seq;Clinical;cohort;Data;Data Set;deprivation;Development;DNA Polymerase II;enzalutamide;Epithelium;Experimental Models;experimental study;EZH2 gene;Future;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Genes;Genomics;Gleason Grade for Prostate Cancer;Goals;In Vitro;in vivo;inhibitor;Intervention;Invaded;Investigation;Knowledge;LNCaP;Malignant neoplasm of prostate;Mediating;men;Mission;Monitor;mouse model;Neoplasm Metastasis;new therapeutic target;novel;novel therapeutics;overexpression;Pathway interactions;Phenotype;promoter;Prostate;prostate cancer cell;prostate cancer cell line;prostate cancer metastasis;prostate cancer progression;Prothrombin;recruit;Resistance;response;Role;stemness;targeted treatment;Testing;The Cancer Genome Atlas;Therapeutic Intervention;transcription factor;transcriptomics;tumor;tumor progression;Veterans;YY1 Transcription Factor

PROJECT_TITLE: The Role of PDEF in Prostate Cancer


ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: Lung cancers are endowed with important antigen presenting cells (APCs), including “professional” APCs known as dendritic cells, that ideally drive anti-cancer immunity by presenting characteristic tumor “antigens” or signatures to killer T-cells of the immune system. Building on initial work in which we genetically altered unique sugar-polymers on dendritic cells to augment “tumor-kill” responses by such T cells, we here aim to study how broader genetic targeting of sugars (including sialic acids in addition to sulfated glycan polymers) on a broader repertoire of APCs in lung cancer may potently boost anti-tumor immunity. We will employ novel APC-targeting approaches in lung cancer models as well as human lung cancers to demonstrate how such targeting may serve as a pre-clinical approach to induce specific anti-tumor immunity through a strategy that is geared to respond to host specific tumor immune signatures in real time: This provides a basis for the design of curative immune-targeted lung cancer therapy that will uniquely “keep pace” with the tumor-immune landscape.

PI_NAMEs: FUSTER, MARK M (contact)

PROJECT_TERMS: Affect;anti-cancer;Antigen Presentation;Antigen-Presenting Cells;Antigens;Antisense Oligonucleotides;autoimmune toxicity;Automobile Driving;Bone Marrow;Cancer Model;cancer therapy;Carcinoma;CD8-Positive T-Lymphocytes;Cell Surface Receptors;Cells;Cellular Immunity;Characteristics;checkpoint therapy;Complement;Cytolysis;cytotoxic CD8 T cells;Cytotoxic T-Lymphocytes;Dendritic Cells;design;Disease remission;Effector Cell;Endowment;engineered T cells;Excision;exhaustion;Family;Genetic;Genetic Induction;Glycocalyx;Goals;Heparitin Sulfate;Human;Immune;immune checkpoint;immune checkpoint blockade;Immune system;Immune Targeting;improved;in vivo;Infiltration;inhibitor;insight;Ligation;Lung;Lung Carcinoma;Lung Neoplasms;Lymphatic;Lymphatic Endothelial Cells;Lymphatic Endothelium;Malignant neoplasm of lung;Marrow;Measures;Mediating;Methods;Modeling;mouse model;Mus;Mutation;neoantigens;novel;Pathway interactions;Physiologic pulse;Polymers;Polysaccharides;pre-clinical;Process;Proliferating;Proteoglycan;Reporting;Repression;response;sensitizing antigen;Sialic Acids;sialylation;Specificity;Structure;sugar;Sulfate;Surface;System;T cell response;T-Cell Proliferation;T-Cell Receptor;T-Lymphocyte;TCR Activation;Technology;Testing;Therapeutic;Time;tumor;Tumor Antigens;Tumor Burden;tumor growth;Tumor Immunity;tumor microenvironment;Work

PROJECT_TITLE: Glycocalyx Targeting and Augmenting Cellular Immunity in Lung Cancer


ORG_CITY: LONG BEACH

PHR: Project Narrative This CMA3 project proposes to test anti-carcinogenic and antitumor efficacy of novel LSD1 inhibitors in a tobacco carcinogen induced tumor model and in patient-derived bladder cancer organoid and xenograft lines representative of early invasive bladder cancer (i.e. Ta or T1 + carcinoma in situ). Biomarkers or expression signatures for predicting the anti-tumor responses of the LSD1 inhibitors will also be identified.

PI_NAMEs: ZI, XIAOLIN  (contact)

PROJECT_TERMS: 4-biphenylamine;Address;Antitumor Response;Artificial Intelligence;artificial intelligence algorithm;Artificial Intelligence enhanced;Award;Bacillus Calmette-Guerin Therapy;base;Binding;Biological Warfare;biomarker driven;biomarker identification;biomarker signature;Bladder;bladder cancer prevention;bladder carcinoma in situ;Blood;Cancer Biology;Cancer Burden;cancer cell;Cancer Detection;cancer initiation;Cancer Patient;cancer risk;cancer stem cell;cancer subtypes;carcinogenesis;Carcinogens;Carcinoma in Situ;Cause of Death;Cells;Chemicals;Chemopreventive Agent;Colorectal Cancer;comparison control;Control Groups;Cystoscopy;Cytokeratin-8 Staining Method;Data;Detection;Development;Diagnosis;differential expression;Disease;E2F transcription factors;Early Diagnosis;Early treatment;effective therapy;Eligibility Determination;Ensure;Epigenetic Process;epigenetic therapy;Epithelium;Evaluation;exome sequencing;Exposure to;EZH2 gene;Foundations;Future;GATA3 gene;Gene Expression Profile;Genes;Genetic;Genetic Transcription;Genomics;Goals;Growth;Hazardous Chemicals;high risk;Histones;Human;image guided;imaging biomarker;Imaging technology;Immune;Immunotherapy;improved;in vivo;Indolent;inhibitor;Intercept;Invaded;Invasive Lesion;Kava;KDM1A gene;Knowledge;Legal patent;Lesion;Link;Lysine;Maintenance;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant neoplasm of urinary bladder;Malignant Neoplasms;Mediating;Medical center;Methods;methyl group;Methylation;Mixed-Lineage Leukemia;Modeling;Molecular;molecular marker;Molecular Profiling;molecular subtypes;Mus;Muscle;muscle invasive bladder cancer;Mutate;Neoplasm Metastasis;new therapeutic target;Nitrosamines;non-smoker;Normal Cell;novel;novel diagnostics;novel strategies;novel therapeutics;Occupational Exposure;Operative Surgical Procedures;Organoids;overexpression;Pathway interactions;patient derived xenograft model;patient response;Patient Self-Report;Patients;personalized management;Play;PPAR gamma;Precision therapeutics;predicting response;predictive signature;Predictive Value;prevent;Prevention;Prevention trial;Primary Care;Reagent;Recommendation;Recording of previous events;Recurrence;Reporting;research and development;Resources;response;Risk;risk stratification;Role;Scientist;screening guidelines;Screening procedure;Second Primary Neoplasms;Smoker;Smoking;success;synergism;Testing;Therapeutic;therapy resistant;Time;Tobacco;tobacco exposure;Tobacco smoke;Tobacco smoking behavior;Tobacco-Associated Carcinogen;TP53 gene;Transcriptional Regulation;transcriptome sequencing;Treatment Efficacy;treatment response;treatment trial;tumor;tumor progression;Tumor Suppressor Proteins;tumorigenic;urinary;Urine;Urologic Surgical Procedures;Urothelium;Veterans;Xenograft procedure

PROJECT_TITLE: CMA-Basic and Translational Mechanisms of Cancer Initiation of the Urothelium in Veterans Exposed to Carcinogens: Interception of tobacco smoking-related bladder cancer by an epigenetic approach


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

ORG_CITY: HOUSTON

ORG_DEPT: PEDIATRICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE (Relevance Statement) Epigenetics refers to the study of mitotically heritable changes in gene function without accompanying DNA sequence alterations; of the three known epigenetic mechanisms, DNA methylation stands out as the most stable epigenetic mark. The proposed research is relevant to public health because it will advance our understanding of how aberrant DNA methylation, frequently observed in lung cancer patients, drives tumor development. The proposed project will also contribute significantly to the ongoing search for new and improved strategies of cancer therapy and prevention.

PI_NAMEs: SHEN, LANLAN  (contact)

PROGRAM_OFFICER_NAME: BENAVIDEZ, JUSTIN MICHAEL

PROJECT_TERMS: Aberrant DNA Methylation;Acceleration;Adenocarcinoma;Affect;Alleles;Animal Model;anti-cancer research;anti-PD-L1;Benign;Biological Models;Cancer Etiology;cancer initiation;Cancer Model;Cancer Patient;cancer prevention;Cancer Prognosis;cancer therapy;Cell Aging;Cell Communication;Cell Cycle Regulation;Cell Physiology;Cells;clinically relevant;combinatorial;Communities;Complex;Cyclin-Dependent Kinase Inhibitor 2A;Development;Disease;DNA Methylation;DNA Methyltransferase Inhibitor;DNA Sequence Alteration;Drug Targeting;Engineering;Epigenetic Process;epigenetic silencing;epigenetic therapy;Epithelium;Etiology;Event;gene function;Gene Mutation;gene regulatory network;Gene Silencing;Gene Targeting;Genes;Genetic;Genetically Engineered Mouse;Goals;HDAC4 gene;Heritability;Histone Deacetylase Inhibitor;Human;human model;immune checkpoint;Immunocompetent;Immunotherapy;improved;in vivo;insight;Intervention;KRAS2 gene;Laboratories;Lead;Lentivirus Vector;Lesion;Link;Lung;Lung Adenocarcinoma;lung development;Lung Neoplasms;lung tumorigenesis;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;malignant phenotype;Methylation;Mitotic;Modeling;Molecular;Monitor;mouse model;Mus;mutant;Mutation;Neoplasm Metastasis;Non-Malignant;novel;Oncogenes;Oncogenic;organoid transplantation;Organoids;Pathway interactions;Pattern;Phenotype;Prevention;programmed cell death ligand 1;promoter;Public Health;Publishing;Research;Research Project Grants;Role;senescence;single-cell RNA sequencing;Stress;Survival Rate;System;targeted treatment;Testing;Therapeutic;transcriptome sequencing;translational model;Translational Research;treatment response;tumor;tumor growth;tumor microenvironment;tumor progression;Tumor Suppressor Genes;tumorigenesis;tumorigenic;Work

PROJECT_TITLE: Epigenetically Engineered Mouse Model for Lung Cancer Therapy

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


NIH_SPENDING_CATS: Bioengineering;Genetics;Human Genome

ORG_CITY: MADISON

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Spatial RNA-sequencing is a revolutionary new technology that allows us to address scientific questions that were elusive just a few years ago. However, to achieve its potential, novel statistical methods are required for spatial RNA-seq data analysis. The proposed methods address some of the most important statistical and computational deficits facing investigators using spatial RNA-seq. Their development is required to prevent inaccurate inference and to ensure that maximal information is obtained from spatial RNA-seq experiments.

PI_NAMEs: KENDZIORSKI, CHRISTINA  (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Address;Affect;Area;Bar Codes;Binding;Biological;biological systems;Case Study;Cell Lineage;Cells;Collaborations;Communication;Communities;Computer software;Coupled;Data;Data Analyses;Dependence;Detection;Development;Diagnostic;differential expression;Disease;Ensure;experimental study;Gene Expression;Genes;Genome;Genomics;Health;Hemorrhage;improved;insight;interest;laboratory experiment;Maps;Measurement;Measures;Messenger RNA;Methods;Molecular;Morphologic artifacts;mRNA Expression;new technology;Noise;novel;Pathway interactions;prevent;Protocols documentation;Regulation;Research;Research Personnel;Signal Transduction;simulation;single-cell RNA sequencing;Slide;Solid;Source;Spottings;Statistical Methods;Structure;System;Technology;tissue fixing;Tissue imaging;Tissues;tool;trait;transcriptome sequencing;transcriptomics;Variant;Visualization

PROJECT_TITLE: Statistical methods for spatial RNA sequencing experiments

STUDY_SECTION: BMRD

STUDY_SECTION_NAME: Biostatistical Methods and Research Design Study Section[BMRD]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Gene Therapy;Genetics;Human Genome

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: I pioneered many aspects of the microRNA (miRNA) field, e.g. discovering key roles for microRNAs in development, aging and cancer and translating these discoveries towards the clinic. Here I outline my vision of unifying miRNA profiling in individual tumors with functional testing for actionable miRNAs and targeted delivery, with an eye towards personalized miRNA-based therapeutics targeted to the patient’s tumor, and ultimately testing the possibility of integrating miRNAs into standard of care for cancer patients. These studies will be a significant step towards developing precision miRNA therapeutic approaches that could be efficacious in lethal cancers affecting hundreds of thousands of Americans.

PI_NAMEs: SLACK, FRANK J. (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: 3' Untranslated Regions;Affect;Aging;Alleles;American;Animal Model;Area;Biological Assay;cancer biomarkers;Cancer Patient;Cell Cycle;Cell Line;Cells;Charge;Clinic;Clinical;clinical application;Clinical Investigator;Clinical Trials Unit;Collaborations;Communities;Coupled;design;Development;Diagnostic;Disease;Future;Genome;Goals;Human;immune checkpoint;Immune Targeting;Individual;Malignant Neoplasms;medical schools;Medicine;Metabolism;Methods;microRNA delivery;MicroRNAs;miRNA expression profiling;mouse model;Neoplasm Metastasis;Non-Small-Cell Lung Carcinoma;novel;novel strategies;Oncogenes;Organoids;Pathway interactions;Patients;personalized medicine;personalized therapeutic;Phase I Clinical Trials;Physicians;pre-clinical;Process;profiles in patients;programs;Proliferating;Regimen;Research;Resources;RNA;Role;screening;standard of care;success;targeted delivery;Testing;theranostics;Therapeutic;therapeutic miRNA;therapeutic target;Tissues;Transcript;Translating;Translations;tumor;Tumor Tissue;Untranslated RNA;Validation;Vision;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Precision microRNA medicine in cancer


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Down Syndrome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurodegenerative;Neurosciences;Pediatric;Prevention

ORG_CITY: TUSCALOOSA

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF ALABAMA IN TUSCALOOSA

PHR: NARRATIVE The proposed study will identify early-occurring declines in cognitive and other functions in young people with Down Syndrome. In the long term, this knowledge would open the door to early pharmaceutical, behavioral, or environmental interventions that could improve quality of life and possibly slow the progression of early aging and Alzheimer's disease among adults with DS.

PI_NAMEs: CONNERS, FRANCES A (contact)

PROGRAM_OFFICER_NAME: BARDHAN, SUJATA

PROJECT_TERMS: 20 year old;Acceleration;Adaptive Behaviors;Address;Adolescence;Adolescent;Adult;Affect;Age;aged;Aging;aging process;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer’s disease biomarker;Amyloid;behavior measurement;Behavior Therapy;Behavioral;Biochemical;Brain;Chromosome 21;Clinical;Cognitive;Cognitive aging;cognitive change;cognitive function;cognitive testing;Dementia;design;Detection;Development;Developmental Course;Diagnosis;Disease Management;Disease Progression;Down's Syndrome;Early identification;Educational workshop;emerging adult;environmental intervention;Episodic memory;Etiology;Event;executive function;Face;Funding;Future;Gait;General Population;Goals;Head;healthy aging;high risk;Impaired cognition;improved;Individual;instrument;Intellectual functioning disability;Investigation;Knowledge;Language;Life;life span;Link;Longitudinal Studies;maladaptive behavior;Matched Group;Measures;medical vulnerability;Memory;Mental Depression;mental state;mild cognitive impairment;National Institute of Child Health and Human Development;Natural History;neuropathology;non-verbal;older adult;Outcome;Participant;participant enrollment;Pathologic;Performance;Persons;Pharmacologic Substance;phonology;Population;pre-clinical;Premature aging syndrome;progression marker;Quality of life;Reporting;Research;Research Project Grants;Signal Transduction;skills;Sleep Disorders;Specificity;Speed;Symptoms;Syndrome;tau Proteins;therapy design;Thyroid Function Tests;Time;trend;United States National Institutes of Health;Update;Vocabulary;young adult;Youth

PROJECT_TITLE: Early Cognitive Decline in Down Syndrome

STUDY_SECTION: CPDD

STUDY_SECTION_NAME: Child Psychopathology and Developmental Disabilities Study Section[CPDD]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Chronic Pain;Contraception/Reproduction;Endometriosis;Infertility;Nanotechnology;Pain Research;Stem Cell Research;Stem Cell Research - Embryonic - Human;Women's Health Research

ORG_CITY: EAST LANSING

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: MICHIGAN STATE UNIVERSITY

PHR: Project Narrative Target delivery of anti-inflammatory naodrugs can replace the current surgical and hormone treatment for endometriosis. We will dissect the molecular mechanism of pSTAT3 on endometriosis-specific inflammation and immune suppression. We will test the therapeutic effects of antioxidant nanoceria on endometriosis progression, pain, and infertility using a mouse model and in vivo imaging.

PI_NAMEs: JEONG, JAE-WOOK ;KIM, TAEHO  (contact)

PROGRAM_OFFICER_NAME: AHN, HELENA HYESOOK

PROJECT_TERMS: Affect;Age;Albumins;angiogenesis;Animal Model;Animals;Anti-Inflammatory Agents;Antioxidants;catalase;cerium oxide nanoparticle;chronic pelvic pain;Contrast Media;Development;Diagnosis;Disease;Elements;Endometrial;endometriosis;endometriosis-related infertility;Enzymes;Estrogens;eutopic endometrium;Excision;Extravasation;fertility improvement;Fetal Development;Fluorescent Dyes;Functional disorder;Goals;Growth;high risk;Hormonal;Hormones;Human;human tissue;image guided;immunoregulation;Immunosuppression;implantation;improved;in vivo imaging;Incidence;Indocyanine Green;Infertility;Inflammation;Inflammatory;inhibitor;Injections;innovation;insight;Lesion;Macrophage;Mediating;Medical;Medicine;Menstrual cycle;mineralization;Modeling;Molecular;mouse model;Multimodal Imaging;nanodrug;nanoparticle;Non-Steroidal Anti-Inflammatory Agents;novel;novel strategies;Operative Surgical Procedures;Optics;overexpression;Pain;pain reduction;pain relief;pain symptom;Permeability;Peroxidases;Pharmaceutical Preparations;Phenotype;Phosphorylation;photoacoustic imaging;Play;pre-clinical;Pregnancy;Process;Proteins;real time monitoring;Recurrent disease;reduce symptoms;relapse risk;Reporting;reproductive;Risk;Role;side effect;Signal Transduction;Stat3 protein;targeted delivery;targeted treatment;theranostics;Therapeutic;Therapeutic Effect;therapeutic evaluation;Tissues;tool;Toxic effect;Woman

PROJECT_TITLE: Development of anti-inflammatory nanodrug for endometriosis treatment

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


FUNDING_MECHANISM: OTHERS

ORG_CITY: LOS ANGELES

ORG_NAME: VA GREATER LOS ANGELES HEALTHCARE SYSTEM

PHR: Despite the hundreds of thousands of tendon repairs and ligament reconstructions performed each year in the United States, clinically there is still no effective strategy to regenerate the complex tissue organization of native tendon and ligament attachments to bone (the enthesis). The goal of this proposal is to; 1) compare the efficacy of targeted delivery of biologically relevant growth factors BMP-2 and NELL-1 to promote enthesis regeneration; and 2) develop novel biomimetic scaffolds that facilitate local delivery of these factors in an environment that has favorable micro-mechanical enthesis-like properties. It is anticipated that these innovative approaches to the fundamental problem of enthesis generation will shift the current paradigm of treating musculoskeletal soft tissue injuries.

PI_NAMEs: KREMEN, THOMAS JOHN (contact)

PROJECT_TERMS: 3D Print;Acceleration;Affect;Age;Animal Model;anterior cruciate ligament injury;anterior cruciate ligament reconstruction;anterior cruciate ligament rupture;Architecture;Award;Back;Biological;Biology;Biomechanics;Biomimetics;bisphosphonate;BMP2 gene;bone;bone cell;bone healing;career;career development;Cartilage;cathepsin K;Cellular Morphology;Clinical;clinical efficacy;Clinical Trials;comparative efficacy;compare effectiveness;Complex;Coupled;Data Analyses;design;Development;drug discovery;Environment;Exhibits;Exposure to;Extracellular Matrix;Failure;Financial Support;Fluorochrome;Funding;Generations;Goals;graduate school;Grant;Growth Factor;healing;Implant;implantation;improved;in vivo;Incidence;Inferior;Injury;innovation;insight;Institution;Instruction;International;Laboratories;Ligaments;Link;Measures;Mechanics;medical specialties;Mentors;Mentorship;Mesenchymal Stem Cells;Military Personnel;Molecular Chaperones;Muscle;Musculoskeletal;musculoskeletal injury;Natural regeneration;novel;novel strategies;Operative Surgical Procedures;Orthopedics;osteochondral tissue;Osteoclasts;Outcome;Parents;Peptide Hydrolases;Persons;Physiologic Ossification;Population;Positioning Attribute;pre-clinical assessment;Procedures;Process;Property;Proteins;reconstitution;reconstruction;repaired;Research;Role;Rotator Cuff;Rupture;Savings;scaffold;Scientist;Site;Skeleton;Societies;soft tissue;Soft Tissue Injuries;Specialist;Sports Medicine;square foot;stem cells;Structure;Surgeon;targeted delivery;Technology;Tendon structure;Time;Tissues;Training;Training Programs;Translational Research;translational scientist;transmission process;United States;United States National Institutes of Health;Use Effectiveness;Work

PROJECT_TITLE: Enhanced Soft Tissue-to-Bone Healing via Treatment with Novel Growth Factor NELL-1: Targeted Delivery and Biomimetic Scaffolds


ORG_CITY: SYRACUSE

ORG_NAME: SYRACUSE VA  MEDICAL CENTER

PHR: Project Narrative: Relevance to Veterans Health Corneal scarring and glaucoma are major causes of blindness among veterans, active military and civilians. Our proposed studies aim to prevent and reverse corneal scarring, and prevent scarring in the eye after glaucoma filtration surgery. Our patented self-delivery siRNA has demonstrated efficacy in these two indications in vivo. Gene knockdown by self-delivery siRNA is effective for 2-3 months. It is a novel solution to improving vision, avoiding the need for constant dosing, without the potential issues related to long term viral-mediated gene knockdown or overexpression. Successful completion of this project will advance translation of our therapeutic towards human clinical trials to prevent blindness from corneal injury and glaucoma in veterans.

PI_NAMEs: BERNSTEIN, AUDREY M (contact)

PROJECT_TERMS: 3-Dimensional;Actins;Acute;age related;age-related disease;Aging;Animals;antifibrotic treatment;Apoptosis;Award;Binding;Biological;Blindness;Brain Injuries;Bulla;Burr hole procedure;C-terminal;Cell Adhesion;Cell Proliferation;Cells;Cholesterol;Chronic;Cicatrix;Clinical;Clinical Trials;Collagen;Cornea;corneal burn;Corneal Injury;corneal regeneration;corneal scar;cost;Cost Savings;Cytoskeleton;Data;Development;disability;Dose;Endothelium;Exhibits;experimental study;Extracellular Matrix;Eye;Eye Injuries;Family suidae;Fibroblasts;Fibronectins;Fibrosis;Filtering Surgery;Filtration;Flow Cytometry;Freedom;G3BP1 gene;Gel;General Population;Genes;Glaucoma;glaucoma surgery;Goals;healing;Health;Hour;Human;immune cell infiltrate;Immunohistochemistry;improved;in vivo;Induction of Apoptosis;Inflammation;inhibitor;Injury;Integral Membrane Protein;Integrin alphaV;Integrins;irritation;knock-down;Legal patent;Length;Link;Mediating;Methodology;Microscopy;Military Personnel;Mitomycin C;Modification;Myofibroblast;N-terminal;neovascularization;Nerve Regeneration;novel;operation;Operative Surgical Procedures;Organ Culture Techniques;Oryctolagus cuniculus;Outcome;overexpression;Pathologic;Pathway interactions;Penetration;Pharmaceutical Preparations;Physiologic Intraocular Pressure;Pilot Projects;Play;Population;pressure;prevent;Proliferating;Publishing;Quality of life;Recycling;regenerative healing;Role;Sclera;Services;slit lamp imaging;Speed;standard of care;Structure;surgery outcome;targeted treatment;Techniques;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;Thick;Time;Tissues;tonometry;Toxin;TP53 gene;Translations;Trauma;Ubiquitin;ubiquitin isopeptidase;Ubiquitination;Veterans;Viral;Vision;Visual;Visual disability;Visual impairment;Work;wound;wound closure;wound healing

PROJECT_TITLE: A Self-Delivery siRNA for Promoting Regenerative Healing in the Eye