ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Narrative Initiation of nuclear DNA replication is tightly regulated such that the entire genome is duplicated exactly once in every cell division cycle. Deregulation of the mechanisms that control this process provokes genomic instability and fuels malignant transformation, but is also the underlying cytotoxic activity of a new anti-cancer therapeutic approach. In this proposal, we characterize the genomic abnormalities that arise when these mechanisms are derailed both in cancer and non-cancer cells and investigate the molecular activities that participate in the generation of these abnormalities. A full understanding of this process will guide the development of better strategies to treat cancer.

PI_NAMEs: ABBAS, TAREK A. (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Affect;anti-cancer therapeutic;Bioinformatics;cancer cell;Cell Cycle;Cell Line;cell type;Cells;Characteristics;Chromatin;Chromosomes;Complement;Complex;cytotoxic;design;Development;DNA biosynthesis;DNA Double Strand Break;DNA Repair;DNA Repair Gene;DNA Replication Induction;DNA replication origin;DNA-PKcs;Double Strand Break Repair;Enzymes;Epigenetic Process;epigenetic regulation;Eukaryota;Exhibits;Failure;Fire - disasters;Fluorescent in Situ Hybridization;G1 Phase;gene repression;Gene Silencing;Generations;Genes;Genetic Engineering;Genome;genome sequencing;Genomic Instability;genomic locus;Genomic Segment;Genomics;Goals;histone methyltransferase;Histones;improved;innovation;L3MBTL1 gene;Licensing;Malignant - descriptor;Malignant Neoplasms;Mammalian Cell;Mediating;Methylation;Methyltransferase;Mitosis;Modeling;Molecular;mutant;Nature;novel;Nuclear;pharmacologic;Population;Process;Proteins;Reader;recruit;Regulation;Replication Initiation;Replication Licensing;Replication Origin;Resistance;Role;S phase;Site;Sorting;Stochastic Processes;Testing;Transcription Repressor;Transcriptional Regulation;Transferase;whole genome

PROJECT_TITLE: Regulation of re-replication in mammalian cells

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: SEATTLE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative We have discovered that the DNA repair enzyme DNA-PK activates a potent antiviral response in human cells, but not laboratory mice. We will explore the therapeutic potential of triggering DNA-PK in human tumors to enhance cancer immunotherapy.

PI_NAMEs: RONGVAUX, ANTHONY ;STETSON, DANIEL B (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Anti-viral Response;antigen-specific T cells;antiviral immunity;Biology;cancer immunotherapy;Cell Line;Cells;Clinical Trials;Complex;Development;DNA;DNA Damage;DNA Repair Enzymes;DNA-dependent protein kinase;effector T cell;Engraftment;Goals;Human;humanized mouse;Immune;immune checkpoint blockade;Immune response;In Vitro;in vivo;Infiltration;Inflammation;Interferon Type I;Interferons;IRF3 gene;Laboratory mice;Malignant Neoplasms;Mediating;Melanoma;Melanoma Cell;metastatic process;Modality;Modeling;mouse model;Mus;Myelogenous;Myeloid Cells;Myeloproliferative disease;neoplastic cell;Nonhomologous DNA End Joining;novel;Outcome;Pathway interactions;Patients;phosphoproteomics;Phosphorylation;preclinical evaluation;Production;recruit;repaired;response;sensor;Signal Transduction;Solid Neoplasm;Stimulus;STING agonists;T cell infiltration;Testing;Therapeutic;Therapeutic Effect;tumor;Tumor Antigens;tumor microenvironment;Viral

PROJECT_TITLE: Activation of the DNA-PK-dependent antiviral response as a novel cancer immunotherapy

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Neurosciences;Precision Medicine

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Project Narrative  There is increasing interest in using immunotherapy or targeted therapy to treat brain metastases, including leptomeningeal disease from cancer. However, it can be challenging to interpret response to treatment or to understand patterns of response or resistance to treatment since serial tissue samples are difficult to obtain from brain metastases. The goal of this proposal is to use circulating tumor DNA and sophisticated MRI scans to characterize the biological response of brain metastases to immunotherapy and targeted therapy by monitoring circulating tumor DNA burden and clonal evolution during treatment and comparing these to changes on MRI.

PI_NAMEs: BRASTIANOS, PRISCILLA KALIOPI;GERSTNER, ELIZABETH  (contact)

PROGRAM_OFFICER_NAME: WANG, YISONG

PROJECT_TERMS: Address;Anatomy;Biological;Biological Markers;Blood;Blood Vessels;Brain;brain magnetic resonance imaging;Breast;burden of illness;Cellularity;chemotherapy;Clinical;Clinical Trials;Clonal Evolution;Collection;contrast enhanced;Data;Data Set;Disease;Genes;genetic evolution;Genetic Heterogeneity;Goals;Histology;Image;immune activation;Immune system;Immunotherapy;immunotherapy trials;improved;improved outcome;Inflammation;insight;interest;Leptomeninges;Location;Magnetic Resonance Imaging;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Mediating;Metastatic malignant neoplasm to brain;Metastatic Neoplasm to the Central Nervous System;Monitor;MRI Scans;Mutation;novel therapeutics;Pathway interactions;patient population;patient subsets;Patients;Pattern;PD-1 inhibitors;pembrolizumab;Perfusion;Pharmaceutical Preparations;Physiological;Play;radiological imaging;Resistance;responders and non-responders;response;response biomarker;Role;Shapes;survival prediction;targeted treatment;Tissue Sample;Tissues;tool;treatment response;trial enrollment;tumor;Tumor Burden;tumor DNA;tumor growth;tumor microenvironment;tumor progression;Vertebral column;Work

PROJECT_TITLE: Using MRI and circulating tumor DNA to improve the interpretation of response to immunotherapy and targeted therapy in CNS metastases

STUDY_SECTION: CBSS

STUDY_SECTION_NAME: Cancer Biomarkers Study Section[CBSS]


NIH_SPENDING_CATS: Behavioral and Social Science;Breast Cancer;Cancer;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Complementary and Integrative Health;Cost Effectiveness Research;Disability Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Networking and Information Technology R&D (NITRD);Pain Research;Palliative Care;Prevention;Rehabilitation;Rural Health;Social Determinants of Health;Telehealth;Women's Health Research

ORG_CITY: DURHAM

ORG_DEPT: PSYCHIATRY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Relevance This research is relevant to public health because it aims to improve quality of life in the many US patients with cancer who live in medically underserved areas with a non-pharmacological approach to pain management. This innovative work will demonstrate the efficacy of a behavioral cancer pain intervention delivered by mHealth technology (i.e., video- conferencing with a remote therapist in the patients community based oncology clinic and home-extension with a basic smartphone) to decrease pain and disability; demonstration of efficacy has a high potential to lead to rapid wide-spread use, particularly benefiting individuals who face significant barriers (e.g., access, distance, financial, time, low literacy) to traditional behavioral interventions. The project is relevant to NIH’s mission because it aims to use a non-pharmacological approach reduce pain that incurs burden and disability and increase quality of life in patients with cancer.

PI_NAMEs: SOMERS, TAMARA J (contact)

PROGRAM_OFFICER_NAME: STRECK, BRENNAN PARMELEE

PROJECT_TERMS: Address;Adherence;arm;Arthritis;attentional control;Behavior Therapy;Behavioral;behavioral health;Breast Cancer Patient;cancer care;cancer pain;Cancer Patient;Caring;Cellular Phone;Chronic disability;chronic pain patient;Clinic;Communities;community clinic;community intervention;Control Groups;coping;Coping Skills;cost;Cost Analysis;cost effective;cost effectiveness;cost per quality-adjusted life year;Cost Savings;cost-effectiveness evaluation;Data;design;disability;Distress;Doctor of Philosophy;Education;Educational Intervention;Effectiveness;efficacious intervention;efficacy evaluation;efficacy testing;Face;Fatigue;Feedback;Focus Groups;Future;Goals;Health;health care disparity;Health Services Accessibility;Healthcare;Home;Home environment;Improve Access;improved;improved outcome;Incidence;incremental cost;Individual;innovation;Intervention;Journals;Life;literacy;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Mediator;Medical;Medical center;medically underserved;Medically Underserved Area;mHealth;mhealth interventions;Mission;mobile application;Modeling;Nonpharmacologic Therapy;Oncology;Outcome;Pain;pain catastrophizing;Pain interference;Pain management;pain outcome;pain reduction;Participant;patient population;patient-level barriers;Patients;Persistent pain;Persons;physically handicapped;post intervention;primary outcome;Protocols documentation;psychological distress;psychosocial;Public Health;Quality of life;Randomized, Controlled Trials;Recommendation;recruit;Relaxation;remote therapy;Research;Resources;Rural Community;Sampling;Self Efficacy;Severities;skills training;symptom management;Technology;Testing;Text;therapy design;Time;Training;Transportation;Travel;underserved community;United States National Institutes of Health;Videoconferencing;Woman;Work

PROJECT_TITLE: A Mobile Health Behavioral Pain Intervention Protocol for Breast Cancer Patients with Pain in Medically Underserved Communities: A Randomized Controlled Trial

STUDY_SECTION: BMIO

STUDY_SECTION_NAME: Behavioral Medicine, Interventions and Outcomes Study Section[BMIO]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: NEW HAVEN

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: This research program focuses on the systems developmental biology, biophysics and biomechanics of early spinal column development. The research program utilizes zebrafish as model for understanding the mechanisms of human development and causes of birth defects such as scoliosis and spina bifida. Overall, this is multi-scale research program that considers the roles of molecules, cells and tissues in the genesis of order in the developing embryo.

PI_NAMEs: HOLLEY, SCOTT A (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Biological;Biomechanics;Biophysics;Cell Adhesion Molecules;cell behavior;Cells;Cellular Morphology;Computer Models;Congenital Abnormality;Data Analyses;Development;Developmental Biology;Embryo;Embryology;Embryonic Development;follow-up;Genetic;Human Development;Image;in vivo;in vivo evaluation;insight;Mechanics;Methods;Modeling;Molecular;Morphogenesis;Pattern;Pattern Formation;programs;Protein Dynamics;Reproducibility;Research;Role;scoliosis;single molecule;Spinal Dysraphism;System;Tissues;Vertebral column;Zebrafish

PROJECT_TITLE: The systems developmental biology of zebrafish body elongation

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Congenital Structural Anomalies;Kidney Disease;Pediatric;Rare Diseases

ORG_CITY: CORAL GABLES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE Alport Syndrome (AS) is an inherited disease that affects the kidney, the ear, and the eye; patients with AS often require dialysis early in life. We show that deficiency of a protein named perilipin 5 (PLIN5) affects the respiratory function of podocytes, a key cellular constituent of the kidney filtration barrier. Findings from this proposal may allow for the identification of a new function of a drug called Ezetimibe which was developed for the cure of high cholesterol and may be helpful in preventing kidney disease in AS by regulating PLIN5 expression.

PI_NAMEs: KIM, JINJU  (contact)

PROGRAM_OFFICER_NAME: RANKIN, TRACY L

PROJECT_TERMS: Adipose tissue;Advisory Committees;Affect;Agreement;Apoptosis;Biological;career;career development;Catabolism;Cells;Cholesterol;Collagen Type IV;Committee Members;Coupling;cytotoxicity;Data;Dedications;defined contribution;Development Plans;Diabetes Mellitus;Dialysis procedure;Ear;Ensure;Environment;Experimental Models;Eye;ezetimibe;Failure;Family;Family member;fatty acid metabolism;Fellowship;Filtration;Funding;glomerular basement membrane;glomerular filtration;Goals;Growth;Health;Hereditary Disease;Hereditary nephritis;Human;Hypertriglyceridemia;Image;improved;in vivo;Injury;innovation;Institution;Kidney;Kidney Diseases;Kidney Failure;Knockout Mice;Laboratories;Learning;Life;Link;Lipase;lipid metabolism;lipidomics;Lipids;Lipolysis;Liver;Mediating;medical schools;Medicine;meetings;member;Membrane Potentials;Mentors;Metabolic;Metabolism;Methodology;Microscopy;Mitochondria;mitochondrial dysfunction;mitochondrial membrane;mouse model;Mus;Mutation;Names;Nonesterified Fatty Acids;novel;obese patients;Organelles;overexpression;Pathogenicity;Patients;perilipin;perilipin A;Permeability;Pharmaceutical Preparations;Physiological;Play;podocyte;prevent;Program Development;protein expression;Proteins;Publications;Reader;recruit;Regulation;Renal glomerular disease;Research;research and development;Research Proposals;Research Support;Respiration;Respiratory physiology;restoration;Role;Science;Services;skills;success;Testing;Tissues;Training;Triglycerides;Universities;uptake;Vocational Guidance

PROJECT_TITLE: The role of PLIN5 deficiency in podocyte lipotoxicity and progression of Alport Syndrome

STUDY_SECTION: DDK

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease

ORG_CITY: ATLANTA

ORG_DEPT: PATHOLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: “Integrin adhesion complexes” (IACs) are assemblies of many different proteins, and are crucial for proper attachment of cells to their surroundings. Using the “model worm”, C. elegans, we discovered a molecule that is required for the formation of IACs in muscle, and that deficiency of the comparable molecule in mice and in fruit flies results in a heart muscle defect called “cardiomyopathy”, an often- inherited disease of humans. Using the unique advantages of worms, mice and flies, we will learn how this molecule functions and how the absence of this molecule leads to cardiomyopathy.

PI_NAMEs: BENIAN, GUY MARTIN (contact)

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Adhesions;Age Months;analog;Animals;Automobile Driving;autosome;Biological Models;Caenorhabditis elegans;Cardiomyopathies;Cell membrane;cell type;Cell-Matrix Junction;Cells;Classification;Complex;congenital myopathy;Death Rate;Defect;DH Domain;Dilated Cardiomyopathy;Drosophila genus;Dystrophin;Extracellular Matrix;fly;Focal Adhesions;Genes;Genetic;Genetic Screening;Glycoproteins;GTP Binding;GTPase-Activating Proteins;Heart;Hereditary Disease;Human;human disease;improved;Inherited;insight;Integral Membrane Protein;Integrins;knock-down;Knockout Mice;Learning;Location;Locomotion;loss of function;Mammals;member;Mitochondria;Modeling;Molecular;Mus;Muscle;Muscle Cells;Muscle Contraction;Muscular dystrophy cardiomyopathy;muscular structure;mutant;Mutation;Myocardium;Myofibrils;Nature;Nematoda;Organism;Orthologous Gene;overexpression;PAK-1 kinase;Pathway interactions;Phenotype;Phosphorylation;Phosphotransferases;PIX protein;Population;Prevalence;protein complex;Protein Kinase;Proteins;Publishing;Reporting;Role;Sarcolemma;Sarcomeres;scaffold;Skeletal Muscle;Striated Muscles;System;Testing;transmission process;Ventricular

PROJECT_TITLE: A Model Multi-systems Approach for Understanding the Role of the PIX Pathway in Cardiac Muscle and Cardiomyopathy

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

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

ORG_CITY: LITTLE ROCK

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: PROJECT NARRATIVE  Researchers in the social sciences lack formal training in advanced analytics that may slow progress in understanding complex relationships between social determinants of health and population health outcomes. Multi-disciplinary, team-based science can align research methods in advanced analytics with social science perspectives to produce a new generation of researchers addressing racial and ethnic disparities in healthcare to improve health equity. As the only NIMHD T32 research training program in the state, the proposed program will serve as model to improve disparate population health outcomes in the state, region, and nation.

PI_NAMEs: BONA, JONATHAN ;TILFORD, JOHN M (contact)

PROGRAM_OFFICER_NAME: OLADEINDE, YEWANDE A

PROJECT_TERMS: Arkansas;health disparity;pre-doctoral;Research Training;Training Programs

PROJECT_TITLE: Arkansas Center for Health Disparities T32 Pre-doctoral Research Training Program

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-A(50)]


ADMINISTERING_IC: NS

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Epilepsy;Genetics;Intellectual and Developmental Disabilities (IDD);Lung;Neurodegenerative;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: STORRS-MANSFIELD

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

PHR: Project Narrative Dravet syndrome (DS) is severe form epilepsy with a high mortality rate that is caused mainly mutations in the Scn1a gene which preferentially regulates activity of inhibitory neurons. Despite evidence showing that respiratory failure is a leading cause of death in epilepsy and DS patients' frequently exhibit disordered breathing,mechanisms underlying respiratory dysfunction in DS are unknown. The main goal of this project is to investigate the untested possibility that loss of Scn1a function in brainstem inhibitory neurons directly affect brainstem respiratory centers and serve as a common substrate for both seizure and respiratory dysfunction.

PI_NAMEs: MILLA, BRENDA  (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Affect;Animals;Apnea;Behavioral;Bradycardia;Brain Stem;Breathing;Carbon Dioxide;Cardiac;Cause of Death;Cells;Cessation of life;Chemoreceptors;Death Rate;Development;Diagnostic tests;dravet syndrome;electrical property;Electrophysiology (science);Epilepsy;Exhibits;experimental study;Fever;Foundations;Genes;Genotype;GLYT2;Goals;Heterozygote;Hypoventilation;in vivo;Incidence;inhibitory neuron;insight;Modeling;mortality;Mus;Mutation;neural;Neurons;novel;Pathology;Patients;Phenotype;premature;Prosencephalon;Reporting;Research;Respiration Disorders;respiratory;Respiratory Center;Respiratory Failure;Respiratory physiology;response;Role;SCN1A protein;Seizures;Slice;sudden unexpected death in epilepsy;Testing;Tissues;Transcript;voltage;Whole Body Plethysmography;Work

PROJECT_TITLE: Roles of glycinergic neurons in Dravet syndrome-associated disordered breathing and mortality


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Digestive Diseases;Genetics;Orphan Drug;Pancreatic Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: PROJECT NARRATIVE A possible explanation for failure of standard chemotherapies in pancreatic ductal adenocarcinoma (PDAC) is cellular phenotypic heterogeneity within tumors, which may enable subpopulations of cells to survive therapy and repopulate the tumor. Elimination or re-differentiation of cancer stem-like cells (CSCs) is an attractive strat- egy-- by homogenizing cancer cell phenotypes within tumors, such therapies may suppress tumor progression and lead to improved response to conventional therapies. We hypothesize that disrupting CSC and niche cells can translate into novel therapeutic strategies for PDAC patients, and therefore we propose to identify mecha- nisms that drive the Wnt target gene Lgr5 (expressed by CSCs) and Porcupine+ niche cell states and to ex- plore the therapeutic potential of Wnt inhibitors in PDAC.

PI_NAMEs: TAMMELA, TUOMAS  (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: Ablation;Acyltransferase;addiction;Adult;Alleles;Antineoplastic Agents;Biology;cancer cell;cancer therapy;Cell Compartmentation;Cells;Characteristics;chemotherapy;Colorectal Adenocarcinoma;Complex;conventional therapy;Cyclodextrins;Data;Desmoplastic;Development;Diagnosis;Drug Delivery Systems;Enzymes;Failure;Gene Expression;Gene Expression Profiling;Genetic;Genetically Engineered Mouse;Growth Factor;Heterogeneity;Human;Immune;improved;In Vitro;in vivo;inhibitor;insight;Investments;LGR5 gene;Ligands;Lung Adenocarcinoma;Malignant neoplasm of pancreas;Malignant Neoplasms;Methods;Modeling;Molecular;Mus;mutant;Mutation;Neoplasm Metastasis;Normal tissue morphology;novel therapeutic intervention;novel therapeutics;palmitoylation;Pancreas;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;pancreatic neoplasm;patient derived xenograft model;Patients;Phenotype;Porcupines;Post-Translational Protein Processing;Primary Neoplasm;Proliferating;Property;Proteomics;Reporter;Reporting;Resistance;response;Role;Signal Pathway;Signal Transduction;small molecule;small molecule inhibitor;Solid Neoplasm;stem;stem cells;stem-like cell;subcutaneous;Testing;Therapeutic;therapeutic evaluation;therapeutic target;therapy resistant;Toxic effect;Translating;tumor;tumor progression;ubiquitin ligase;WNT Signaling Pathway

PROJECT_TITLE: Targeting stem-like cells and their niche in pancreatic cancer

STUDY_SECTION: MONC

STUDY_SECTION_NAME: Molecular Oncogenesis Study Section[MONC]


ED_INST_TYPE: OTHER SPECIALIZED SCHOOLS

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Congenital Structural Anomalies;Infant Mortality;Lung;Neonatal Respiratory Distress;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases

ORG_CITY: Princeton

ORG_DEPT: MISCELLANEOUS

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: RELEVANCE Breathing after birth requires coordinated development of the airways and surrounding tissues within the lung. Defects in the mechanical environment of the fetal chest cavity, such as congenital diaphragmatic hernia, disrupt the pressure across the developing lung and lead to abnormal development of the airways. Here we combine an innovative model system to mimic the mechanical environment around developing lungs with transgenic mice to measure the mechanical forces and identify the molecular signals that are activated by pressure, which will suggest new therapeutic targets for the treatment of underdeveloped lungs.

PI_NAMEs: NELSON, CELESTE M (contact)

PROGRAM_OFFICER_NAME: LIN, SARA

PROJECT_TERMS: Address;Affect;Air;airway epithelium;Anabolism;Biochemical;Biological Models;Birth;Breathing;Cells;Chest;Congenital Abnormality;Congenital diaphragmatic hernia;Critical Care;Data;Death Rate;Defect;Development;Embryo;Environment;Epithelium;Equilibrium;experience;fetal;Fetus;fluidity;force sensor;Gene Expression Profile;Genetic Transcription;Growth;Image;Image Analysis;Immunofluorescence Immunologic;Immunohistochemistry;In Situ Hybridization;innovation;Investigation;Knock-out;Knockout Mice;Lead;Liquid substance;Long-Term Survivors;Lung;lung development;Lung Diseases;lung imaging;lung pressure;Measurement;Measures;mechanical force;mechanical signal;Mechanical Stress;Mechanics;Mesenchyme;Mesothelium;Microfluidics;Molecular;Morbidity - disease rate;Morphogenesis;mouse model;Mus;Neonatal Mortality;neonate;new therapeutic target;novel;Nutritional;Pathogenesis;Pathway interactions;Pattern;Phenocopy;pressure;Proliferating;Publishing;pulmonary hypoplasia;quantitative imaging;Quantitative Reverse Transcriptase PCR;Reporter;Reporter Genes;Research Design;Respiratory Diaphragm;respiratory smooth muscle;response;Retinoids;Rodent Model;Role;Secondary to;sensor;Signal Pathway;Signal Transduction;single-cell RNA sequencing;spatiotemporal;System;Testing;Time;Tissues;transcriptomics;Transgenic Mice;Transgenic Organisms;transmission process;Trees;Tretinoin;Work

PROJECT_TITLE: Interplay between mechanical forces and retinoic acid in lung development

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Chronic Pain;Genetics;Neurodegenerative;Neurosciences;Pain Research;Pediatric;Peripheral Neuropathy;Precision Medicine;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: ATHENS

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF GEORGIA

PHR: Project Narrative Peripheral nervous system (PNS) disorders affect a large population world-wide; however, few researchers invest efforts into understanding the causes of PNS disorders, leading to very few treatments available to patients. Familial Dysautonomia (FD) is a rare, genetic and particularly devastating disorder of the PNS, where patients’ symptom severity differs dramatically from mild to severe despite the fact that they all harbor an identical mutation. This project investigates the molecular mechanistic basis of disease severity in FD, using human induced pluripotent stem cells, with the promise of attaining knowledge that will have fundamental implications for FD patients, possibly for other peripheral neuropathies, and will improve our general knowledge about the molecular underpinnings of dysfunction in the PNS.

PI_NAMEs: ZELTNER, NADJA  (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Actins;Affect;Afferent Neurons;Age;Animal Model;Autonomic nervous system;Binding;Biological Assay;blood pressure regulation;Brain;Cadherins;Cell Count;Cell Line;Cells;Chemicals;Childhood;Chinese Traditional Medicine;crosslink;Crosslinker;Defect;Development;Disease;DNA Sequence;Dysautonomias;effective therapy;exome sequencing;Extracellular Matrix;Extracellular Matrix Proteins;Familial disease;Familial Dysautonomia;Frequencies;Functional disorder;Future;Genes;Genetic;genipin;Goals;Heart Rate;human disease;human induced pluripotent stem cells;human pluripotent stem cell;improved;In Vitro;induced pluripotent stem cell;insight;Investments;Kinetics;Knowledge;Laminin;Modeling;Modification;Molecular;Mutation;Neurodegenerative Disorders;Neurons;Nociceptors;novel;Pain;pain sensation;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Peripheral Nervous System;Peripheral Nervous System Diseases;Pharmaceutical Preparations;Phenotype;Point Mutation;Population;precision medicine;Property;Proteins;Reporting;Research;Research Personnel;Sampling;Sensory;Severities;Severity of illness;stem cell technology;Symptoms;Testing;Tissues;tool;Transcription Elongation;Transfer RNA;Vomiting;Work

PROJECT_TITLE: Precision Medicine for the Peripheral Nervous System Disorder Familiar Dysautonomia

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Data Science

ORG_CITY: BALTIMORE

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Many researchers use DNA sequencing to study disease and biology, and analyzing this data requires sophisticated software capable of piecing together puzzles made of billions of fragments of DNA. Mean- while, public archives are ﬁlling with huge datasets that could be used in everyday research, but they are not organized in a convenient way. We propose a set of projects that allow everyday scientists to easily (a) analyze sequencing data, (b) examine archived sequencing datasets to ﬁnd those most relevant to their research, and (c) provide a “search engine” for answering scientiﬁc questions with respect to the archive.

PI_NAMEs: LANGMEAD, BENJAMIN THOMAS (contact)

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: archived data;Archives;Biological;Biological Assay;Biology;Catalogs;Classification;Collection;Computer software;Data;Data Analyses;data archive;Data Science;Data Set;Disease;DNA;DNA sequencing;genomic tools;improved;indexing;Infrastructure;insight;Investigation;Metadata;Metagenomics;Methods;Property;Reporting;Research;Research Design;Research Personnel;RNA;Scientist;search engine;System;tool;Work

PROJECT_TITLE: Methods for sequencing data analysis and archive-scale data science

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


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

ORG_CITY: CHICAGO

ORG_DEPT: PHARMACOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: The major goal of this proposal is to identify genes that contribute to severity of Dravet syndrome, a catastrophic infant-onset epilepsy that includes developmental delays, high mortality risk, and seizures that are difficult to treat with available medicines. Identification of genes that modify disease severity and mortality risk will provide insight into the underlying causes of epilepsy and suggest novel therapeutic strategies for improved treatment of human patients.

PI_NAMEs: KEARNEY, JENNIFER A (contact)

PROJECT_TERMS: 129 Mouse;Address;Affect;Age;Age Months;Alleles;American;Animals;Behavioral;Brain;Buffers;Candidate Disease Gene;cell type;Cells;childhood epilepsy;Chromosome 7;Chromosome 8;Chromosomes;Clinical;Code;Cognitive;Compensation;Complex;Congenic Strain;Data;Data Set;density;Development;Developmental Delay Disorders;differential expression;Disease;DNA;dravet syndrome;Epilepsy;epileptic encephalopathies;Etiology;Evaluation;Exhibits;Failure;Febrile Convulsions;Functional disorder;Gene Expression;Gene Modified;Genes;Genetic;genetic pedigree;Genetic Predisposition to Disease;Genetic Transcription;Goals;Heterozygote;Hippocampus;Human;improved;in vivo;Individual;Infant;Inherited;insight;Intellectual functioning disability;Interneurons;Ion Channel;life span;loss of function;loss of function mutation;Loss of Heterozygosity;Maps;Medicine;mortality risk;Mus;Mutation;Nervous System Disorder;Neurologic;Neurons;neurotransmission;novel therapeutic intervention;Pathogenicity;Pathway interactions;Patients;permissiveness;Persons;Phase;Phenotype;Population;Predisposition;premature;preservation;promoter;Proteins;QTL Genes;Quantitative Trait Loci;Refractory;Reporting;Resistance;Resolution;response;Risk;risk variant;SCN1A protein;Seizures;Severities;Severity of illness;single nucleus RNA-sequencing;single-cell RNA sequencing;Sodium;Sodium Channel;sudden unexpected death in epilepsy;Surveys;Synapses;Syndrome;therapeutic target;trait;Transcriptional Regulation;transcriptome sequencing;Variant;voltage

PROJECT_TITLE: Genetic Modifiers of Childhood Epilepsy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GHD-P(07)S]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: Boulder

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: PROJECT NARRATIVE When exposed to stress, cells move the bulk of their RNA into clumps of RNA and protein called ribonucleoprotein (RNP) granules, seemingly so that they can focus on the specific RNAs that will help them respond to the stress. Different types of RNP granules interact and transfer RNA between themselves during stress, but it is unknown whether these interactions and the transfer of RNA serves an actual role in the cellular stress response. I will improve a tool that allows me to see single molecules of RNA in live cells under a microscope, use that tool to figure out which stress conditions cause RNP granule interactions and the transfer of RNA, and use that tool to test a hypothesis about how RNA is actually transferred between two RNP granules.

PI_NAMEs: RICHARDS, ERIN MARIE (contact)

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: Address;Affect;Alzheimer's Disease;aptamer;Benchmarking;Binding;Biochemical;biochemical tools;Biological;Biology;career;Cell Physiology;Cells;Cellular Stress;Chimeric Proteins;Collaborations;Complex;Cytoplasmic Granules;Data;Data Science;Dementia;design;Detection;Development;Disease;disease stressor;Disputes;Docking;environmental stressor;experimental study;Exposure to;Fellowship;Fluorescence Microscopy;Fluorescent Probes;fluorophore;Foundations;Frequencies;Generations;Genetic Transcription;Goals;Health;Human;Human Genome;Image;Image Analysis;Imaging Device;improved;interest;Knowledge;Life Cycle Stages;Measures;Mediating;Messenger RNA;Microscope;Monitor;mutant;Nature;Nervous System Disorder;Neurodegenerative Disorders;next generation;Northern Blotting;Organism;overexpression;Paint;pointed protein;Positioning Attribute;Probability;Process;Proteins;recruit;Research;response;Ribonucleoproteins;RNA;RNA Binding;RNA-Binding Proteins;Role;Science;Scientist;single molecule;skills;small molecule;Small RNA;sodium arsenite;Stimulus;Stress;stress granule;stressor;System;Testing;Time;Titrations;tool;tool development;Training;Transfer RNA;Translations;Visualization;Western Blotting;Zinc deficiency;Zinc Fingers

PROJECT_TITLE: Using Riboglow to Define RNP Interactions in Response to Environmental Stress

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F05-U(20)L]


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

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: NARRATIVE: Resistance to targeted therapies severely limits their clinical efficacy in metastatic malignancies. Increasing evidence points to DTPs as major reservoirs for enabling stable resistance to develop. Our work will clarify the ontogeny and relevance of DTPs in HER2+ BC.

PI_NAMEs: NEEL, BENJAMIN G.;SKOK, JANE AMANDA (contact)

PROGRAM_OFFICER_NAME: FINGERMAN, IAN M

PROJECT_TERMS: 3-Dimensional;Ablation;Address;Adjuvant Study;Affect;Antineoplastic Agents;Antineoplastic Combined Chemotherapy Protocols;Architecture;Bar Codes;Binding;BT 474;Cancer Biology;Cancer Center;Cancer Etiology;cancer type;Caspase;Cell Line;Cells;chemotherapy;Chimeric Proteins;ChIP-seq;Chromatin;Chromatin Loop;Chromosome Structures;clinical efficacy;cohesin;condensin;conventional therapy;Data;Disease remission;Drug Combinations;Drug Monitoring;Drug resistance;Drug Tolerance;Epigenetic Process;ERBB2 gene;Exhibits;Exposure to;Gene Amplification;Gene Expression;Gene Expression Regulation;Generations;Genes;Genetic Transcription;Growth;In complete remission;in vivo Model;insight;lapatinib;Malignant Breast Neoplasm;Malignant Neoplasms;Mammalian Cell;Mediating;Melanoma;Mesenchymal;Mitosis;Modeling;Molecular;mouse model;Mus;Neoadjuvant Therapy;non-genetic;Non-Small-Cell Lung Carcinoma;novel;novel therapeutics;Oncogenes;Ontology;Pathologic;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phenotype;Play;Population;prevent;programs;promoter;Receptor Protein-Tyrosine Kinases;Reporter;Resistance;Role;Sampling;senescence;Signal Transduction;single-cell RNA sequencing;superresolution microscopy;targeted treatment;Testing;transcription factor TFIIIC;transcriptome;transcriptome sequencing;tumor;tumor growth;tumor-immune system interactions;Tyrosine Kinase Inhibitor;Visualization;Work;Xenograft procedure;Yeasts

PROJECT_TITLE: Molecular ontology of drug tolerant persisters in HER2 positive breast cancer - Resubmission - 1

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


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

ORG_CITY: HADLEY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

PHR: Project Narratives The overall goal of this project is to utilize hypothesis driven experimentation to elucidate key mechanistic processes governing the phytoextraction of arsenic from soil, transport, detoxification and sequestration into above ground biomass. Detailed investigations will focus on biogeochemical processes in the soil that impact contaminant availability to plant roots and also on critical biological limitations and physiological processes that can enable sustained and significant contaminant phytoextraction and hyperaccumulation. This “bottom-up” focus on mechanisms at and within the abiotic-biotic interface will enable the optimization of plant-based remedial strategies for arsenic and facilitate the development of future analogous platforms for additional contaminants.

PI_NAMEs: DHANKHER, OM PARKASH  (contact);VENKATARAMAN, DHANDAPANI ;WHITE, JASON C;XING, BAOSHAN

PROGRAM_OFFICER_NAME: HENRY, HEATHER F

PROJECT_TERMS: absorption;Address;Amendment;arsenate reductase;Arsenic;Binding;Biological;Biological Availability;Biomass;Characteristics;cost effective;Crambe abyssinica;Culture Media;Dedications;Development;Drug Metabolic Detoxication;effectiveness evaluation;Engineering;field study;food chain contamination;Friends;Future;Gene Expression;Gene Transfer;Genes;Genetic;Genetic Engineering;global health;Goals;High Pressure Liquid Chromatography;Human;Hydroponics;Investigation;knock-down;Knowledge;Laboratories;Medial;Metals;Methods;nanoparticle;novel strategies;Oils;Organ;Outcome;overexpression;oxidation;Performance;Physiological Processes;Plant Leaves;Plant Roots;Plants;Process;Public Health;remediation;RNA Interference;Roentgen Rays;screening;Site;Soil;Spectrum Analysis;Structure;Sulfur;surface coating;Testing;tissue culture;Tissues;toxic metal;United States Department of Agriculture;uptake;Vacuole

PROJECT_TITLE: A novel strategy for arsenic phytoremediation


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: PHILADELPHIA

ORG_DEPT: PSYCHOLOGY

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

ORG_STATE: PA

PHR: PROJECT NARRATIVE While the US adult population is approximately 61.3% non-Hispanic white, 17.8% Hispanic or Latino, 13.3% African American, 5.7% Asian, and 1.5% American Indian, Alaskan Native, or Pacific Islander, the picture in academia is much different, with over 85% of full-time faculty identifying as non-Hispanic white or Asian. This loss of diversity is limiting our potential as a nation to build knowledge and improve human health. Our Mid- Atlantic Neuroscience Diversity Scholars (MiNDS) program is a five-year plan to bolster the number of underrepresented minority (URM) students within the neuroscience academic pipeline and build a foundation for URM students to succeed in graduate school and beyond.

PI_NAMEs: OLSON, INGRID R (contact)

PROGRAM_OFFICER_NAME: JONES, MICHELLE

PROJECT_TERMS: Academia;Academic support;Accountability;Admission activity;Adult;African American;Alaska Native;American Indians;Asian;Awareness;Baltimore;Behavioral;bridge program;career;Cognitive;cognitive neuroscience;cohort;college;Color;Communities;Community Outreach;Critical Thinking;Development;Development Plans;Doctor of Philosophy;Education;Educational Curriculum;Educational process of instructing;Educational workshop;Elements;Ensure;experience;Experimental Designs;Faculty;faculty mentor;falls;Financial Support;Five-Year Plans;Fostering;Foundations;Funding;Future;Goals;Graduate Education;graduate school;graduate student;Grant;Health;Hispanic;Home;Human;improved;Individual;insight;Institution;interest;Internships;Interview;Journals;Knowledge;knowledge base;Latino;Lead;lectures;Maryland;meetings;member;Mentors;Mentorship;Neurosciences;Neurosciences Research;Not Hispanic or Latino;Oral;outreach;Pacific Islander;Participant;peer support;Population;Positioning Attribute;Preparation;programs;recruit;Research;Research Personnel;Research Project Grants;Research Training;Scholars Program;Schools;Science;Series;skills;skills training;Societies;statistics;student mentoring;Students;success;summer program;summer research;Techniques;tool;Training;Travel;undergraduate student;Underrepresented Minority;underrepresented minority student;Universities;Work;Writing

PROJECT_TITLE: The Mid-Atlantic Neuroscience Diversity Scholars (MINDS) Program


ORG_CITY: TOLEDO

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS

ORG_STATE: OH

PHR: In the United States, over 80% of prostate cancer patients die with bone metastases. Second line hormonal therapies such as enzalutamide only improve overall patient survival by a few months in about 50% of the patients, and almost all patients develop drug resistance. Thus, there is an urgent need to determine the mechanisms of drug resistance and to develop new approaches for overcoming such resistance and for better treatment of prostate cancer bone metastasis.

PI_NAMEs: LI, XIAOHONG  (contact)

PROJECT_TERMS: androgen independent prostate cancer;Androgen Receptor;bone;Bone Development;Cancer Patient;Cells;cytokine;Cytokine Signaling;Data;Drug resistance;drug resistance development;Endocytosis;enzalutamide;FGF2 gene;Genetic Transcription;Genetically Engineered Mouse;Growth;hormone therapy;improved;insight;Knock-out;Lesion;Malignant neoplasm of prostate;Mediating;Metastatic Neoplasm to the Bone;mouse model;novel;novel strategies;novel therapeutic intervention;Osteoblasts;parathyroid hormone-related protein;Patients;PC3 cell line;pharmacologic;Play;prostate cancer cell;prostate cancer progression;Prostate Cancer therapy;Proteins;recruit;Resistance;Role;small molecule inhibitor;subcutaneous;TGFBR2 gene;Treatment Efficacy;tumor;tumor growth;Tumor Promotion;United States;Up-Regulation;Xenograft procedure

PROJECT_TITLE: Influence of bone microenvironment on drug resistance in prostate cancer bone metastasis

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


NIH_SPENDING_CATS: Clinical Research;Genetics;Hematology;Infectious Diseases;Physical Injury - Accidents and Adverse Effects;Prevention;Sepsis

ORG_CITY: MADISON

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Sepsis is a life-threatening emergency that requires rapid diagnosis of infections and treatment with antibiotics. In trauma patients, diagnosis of sepsis is particularly challenging because initial injury itself can cause physiological derangements that mimic those attributed to infections. In this project, we propose to develop biomarkers to improve diagnostics, clinical management, and outcomes for sepsis in trauma patients using sequencing analysis of circulating microbial DNA in plasma.

PI_NAMEs: KISAT, MEHREEN T (contact)

PROGRAM_OFFICER_NAME: BLATCH, SYDELLA ANNE

PROJECT_TERMS: Address;Antibiotics;antimicrobial;Antimicrobial Resistance;Bacterial DNA;Bioinformatics;Biological Assay;Biological Markers;Blood;Blood specimen;career development;cell free DNA;Cessation of life;Clinical;Clinical Management;Clinical Trials;clinically relevant;Communicable Diseases;Communities;Computing Methodologies;Data;Data Analyses;Dedications;Deterioration;Development;Development Plans;Diagnosis;Diagnostic;diagnostic accuracy;Diagnostic tests;Discipline;DNA;DNA sequencing;early detection biomarkers;Early Diagnosis;Early identification;Emergency Situation;Etiology;experience;genome sequencing;genomic data;Genomics;healthy volunteer;Hospitalization;Hospitals;Hour;improved;improved outcome;Individual;individualized medicine;Infection;Inflammation;Inflammatory Response;Injury;Intensive Care Units;Judgment;Laboratories;Life;Literature;Measures;Medical;Mentorship;metagenomic sequencing;microbial;microbial genomics;Microbiology;Monitor;mortality;Multiple Organ Failure;Operative Surgical Procedures;Organism;Outcome;pathogen;Pathogen detection;Patient Admission;Patients;Physicians;Physiological;Plasma;professor;prospective;radiological imaging;rapid diagnosis;Research;response;response to injury;Sampling;Scientist;Sepsis;Septic Shock;Source;standard of care;Surgeon;systemic inflammatory response;Testing;Time;tissue injury;Training;Translational Research;Trauma;Trauma patient;trauma surgery;Traumatic injury;treatment response;Universities;whole genome;Wisconsin;Withholding Treatment;Work;Writing

PROJECT_TITLE: Improving diagnosis of post-traumatic sepsis using plasma microbial DNA sequencing

STUDY_SECTION: SAT

STUDY_SECTION_NAME: Surgery, Anesthesiology and Trauma Study Section[SAT]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Dementia;Hematology;Infectious Diseases;Mental Health;Neurodegenerative;Neurosciences;Prevention;Sepsis

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Project Narrative The proposed research has direct public health implications through clarifying how delirium is associated with the accumulation of neurodegeneration pathologies and understanding how these pathologies contribute to the development of cognitive decline. As such, this application is immediately relevant to the NIH's mission of fostering innovative research strategies for improving health through identification of the causes, preventive approaches, management of, and novel therapies for, delirium and Alzheimer's Disease and Related Dementias (ADRD). This application will result in novel insights into which Amyloid-Tau-Neurodegeneration pathologies predispose to acute brain dysfunction and delirium, accumulate following delirium, and contribute to the development of ADRD after critical illness.

PI_NAMEs: HUGHES, CHRISTOPHER  (contact);SANDERS, ROBERT D

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Acute;Address;Admission activity;Affect;Age;Aging;Alzheimer disease screening;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease related dementia;Alzheimer’s disease biomarker;Amyloid;Axon;axon injury;biobank;Biological Markers;Blood;blood-based biomarker;brain dysfunction;Brain Injuries;Brain Pathology;Cause of Death;Cerebrospinal Fluid;Cerebrum;Clinical;Clinical Data;Cognition;Cognitive;Cognitive deficits;cognitive function;cognitive interview;cognitive load;Collaborations;Coma;Communities;Complex;Complication;Confusion;cost;Country;Critical Illness;cytokine;Data;Death Rate;Delirium;Dementia;Development;Dexmedetomidine;disability;Disease;Etiology;Fostering;Functional disorder;Funding;Health;Hospitalization;Hypotension;Hypoxia;Impaired cognition;Impairment;improved;Individual;Inflammation;Inflammatory;innovation;insight;Intensive Care Units;interest;Interleukin-8;Intervention Studies;Investigation;Light;Liquid substance;Manuscripts;Measures;Mediating;Mediation;Mediator;Mission;modifiable risk;Morbidity - disease rate;mortality;Nerve Degeneration;Nervous System Disorder;Neurocognitive;neurofilament;Neuronal Injury;Neurons;neuropathology;novel;novel strategies;novel therapeutics;Operative Surgical Procedures;Organ;Organ failure;Pathogenesis;Pathologic;Pathology;Patients;Perfusion;Plasma;postoperative delirium;Postoperative Period;Predisposition;prevent;Preventive;prognostication;Propofol;Proteins;Public Health;Randomized, Controlled Trials;Research;Research Design;response;Risk;Risk Factors;Role;Sampling;secondary analysis;Sedation procedure;sedative;Sepsis;septic;septic patients;Severities;Severity of illness;sex;Stress;tau Proteins;tau-1;Telephone Interviews;Therapeutic;therapeutic target;therapy development;Time;United States National Institutes of Health;β-amyloid burden

PROJECT_TITLE: Delirium, Long-Term Cognition and the Dementia Pathological Trajectory

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE As one of the largest cellular organelles, the endoplasmic reticulum (ER) choreographs the production of virtually all membrane and secretory proteins, along with lipid synthesis and calcium regulation. Critically, the ER cannot be built from scratch in newly divided cells but must be carefully inherited at each cell division; indeed, we found a cell cycle checkpoint termed the ER surveillance (ERSU) pathway that ensures functionally competent ER is inherited at sufficient levels. Dissecting the molecular mechanisms of the ERSU pathway holds great promise to ultimately unveiling the pathogenesis of human diseases caused by uncontrolled cell division, such as cancer.

PI_NAMEs: NIWA, MAHO R (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Anabolism;Behavior;Binding;Biological;biological adaptation to stress;biophysical properties;Calcium;Cell Cycle;Cell Cycle Arrest;Cell Cycle Checkpoint;Cell division;Cell surface;Cells;Cytokinesis;Cytoskeleton;daughter cell;Development;dihydroceramide;Dihydrosphingosine;effective therapy;Endoplasmic Reticulum;endoplasmic reticulum stress;Ensure;Event;event cycle;Exclusion;experimental study;Exposure to;Failure;Generations;Genome;Genomic DNA;Higher Order Chromatin Structure;Homeostasis;human disease;In Vitro;Inherited;Inositol;insight;Integral Membrane Protein;Knock-out;Lipids;Location;Malignant Neoplasms;Mammalian Cell;Mammals;MAP Kinase Modules;Membrane;Membrane Proteins;Mitosis;Mitotic;Mitotic Cell Cycle;model organism;Molecular;Morphology;Mothers;Motion;Neck;next generation;Nuclear;Nuclear Envelope;Organelles;Parents;Pathogenesis;Pathway interactions;pharmacologic;phytosphingosine;Positioning Attribute;Post-Translational Protein Processing;Production;protein expression;Protein Family;Proteins;proteotoxicity;Regulation;response;RNA Viruses;Role;Saccharomyces cerevisiae;secretory protein;segregation;Signal Transduction;Site;Sphingolipids;Stress;stressor;Testing;Transmembrane Domain;Viral;Viral Matrix Proteins;virtual;Work;Yeasts

PROJECT_TITLE: Roles of the ER Stress Surveillance Pathway During the Cell Cycle

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


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Breast Cancer;Cancer;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Patient Safety;Physical Activity;Prevention;Women's Health Research

PHR: PROJECT NARRATIVE Anthracyclines and human epidermal growth factor receptor 2 (HER2)-targeted agents have improved overall breast cancer control and survival; however, the benefits of these cancer therapies are offset by cardiovascular toxicity. Aerobic exercise training (AT) is an effective multimodal strategy that favorably impacts cardiovascular outcomes. Leveraging the infrastructure of a rigorously conducted AT intervention trial in patients with breast cancer, our ancillary biomarker study will evaluate the impact of AT to prevent the cardiovascular toxicity of breast cancer therapy.

PI_NAMEs: YU, ANTHONY FRANCIS (contact)

PROGRAM_OFFICER_NAME: DIMOND, EILEEN

PROJECT_TERMS: Acute;Address;Adjuvant;Adjuvant Chemotherapy;Adverse effects;Aerobic Exercise;Age;Anthracycline;Attenuated;Biological Markers;Biological Specimen Banks;biomarker performance;Blood specimen;Brain natriuretic peptide;Breast Cancer therapy;Breast Cancer Treatment;Cancer Control;Cancer Etiology;cancer survival;cancer therapy;Cardiac;Cardiac Myocytes;cardioprotection;Cardiopulmonary;cardiorespiratory fitness;Cardiotoxicity;cardiovascular effects;cardiovascular injury;Cardiovascular system;cell free DNA;Characteristics;chemotherapy;Clinical;CXCL10 gene;Cyclic GMP;cytotoxic;Data;deconditioning;design;Development;Dose;Early Diagnosis;Educational Intervention;Epidermal Growth Factor Receptor;Exercise;exercise training;Future;Guidelines;health related quality of life;Heart Injuries;Human;Hypertension;Impairment;improved;Inflammation;Inflammatory;Infrastructure;Injury;insight;Interleukin-6;Intervention Trial;Knowledge;Lung;Malignant Breast Neoplasm;Malignant Neoplasms;Measures;mortality;multimodality;Myocardial;Myocardial dysfunction;myocardial injury;Myocarditis;N-terminal;Natriuretic Peptides;Neoadjuvant Therapy;Oncology;open label;Outcome;Pathway interactions;patient subsets;Patients;Physical activity;Physiological;Physiological Adaptation;Play;prevent;Publishing;Radiation therapy;Randomized;Randomized, Controlled Trials;Recommendation;Risk;Risk Factors;risk prediction;Role;Sampling;sarcopenia;Skeletal Muscle;Stimulator of Interferon Genes;Stress;targeted agent;targeted treatment;Toxic effect;Treatment Protocols;Troponin;Troponin I;Woman

PROJECT_TITLE: Effects of Exercise on Changes in Cardiovascular Biomarkers in Patients with Breast Cancer During Anthracycline-based Chemotherapy


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Health Services;Infectious Diseases;Mental Health;Prevention

ORG_CITY: KANSAS CITY

ORG_NAME: CHILDREN'S MERCY HOSP (KANSAS CITY, MO)

ORG_STATE: MO

PHR: PROJECT NARRATIVE In Uganda, fears of relationship dissolution and loss of the ability to have children remain major barriers to HIV in heterosexual couples. Our communication strategy aims to promote HIV testing with reassuring messages about the ability to have stable relationships and healthy families with the increased availability of pre-exposure prophylaxis (PrEP). We will evaluate the feasibility and acceptability of this communication strategy among clients and partners within assisted partner notification and antenatal care programs in two hospitals and evaluate preliminary effects.

PI_NAMEs: HURLEY, EMILY ANNE (contact)

PROGRAM_OFFICER_NAME: SENN, THERESA ELAINE

PROJECT_TERMS: acceptability and feasibility;Adult;Africa South of the Sahara;aged;AIDS prevention;antenatal care;antiretroviral therapy;Attitude;Awareness;Caring;Child;child bearing;Client;Clinic;Communication;community advisory board;Conceptions;condoms;cost effective;Counseling;Couples;Data;Development;Disclosure;Epidemic;Family;Fright;Future;General Population;Goals;Health care facility;Heterosexuals;HIV;HIV Seropositivity;home test;Horizontal Disease Transmission;Hospitals;Human immunodeficiency virus test;Individual;Infection;insight;Intervention;Intervention Trial;Interview;Learning;Link;Mediator;meetings;member;men who have sex with men;Methods;multi-component intervention;Names;National Institute of Mental Health;novel;Outcome;Pamphlets;Partner Notification;Pathway interactions;Persons;Phase;pilot trial;pre-exposure prophylaxis;preservation;prevent;Prevention;Printing;programs;Protocols documentation;Provider;Public Health;Randomized;Randomized, Controlled Trials;Recommendation;Reporting;Research;Risk;Self Disclosure;service uptake;Services;sex;Site;Structure;success;Surveys;System;Telephone;Testing;Training;transmission process;treatment as usual;Uganda;uptake;Vertical Transmission;Work

PROJECT_TITLE: Enhancing communication on relationship preservation, safer conception and PrEP to promote HIV testing

STUDY_SECTION: PPAH

STUDY_SECTION_NAME: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH]


NIH_SPENDING_CATS: Prevention

ORG_CITY: PROVIDENCE

ORG_NAME: MIRIAM HOSPITAL

ORG_STATE: RI

PHR: Narrative Lifestyle factors, including obesity, physical inactivity and smoking, account for more than 50% of the burden of chronic disease morbidity and mortality. This T32 from the Weight Control and Diabetes Research Center in affiliation with the Center of Behavioral and Preventive Medicine at The Miriam Hospital and Brown University trains postdoctoral fellows (primarily PhDs) to become independent researchers with the skills to develop novel interventions to modify these behavioral factors and reduce risk and severity of cardiovascular disease.

PI_NAMEs: THOMAS, JOHN GRAHAM (contact)

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TITLE: Training in Behavioral and Preventative Medicine

STUDY_SECTION: NITM

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


ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Ribosome quality control (RQC) monitors the fidelity of protein synthesis in real-time to ensure that genetic information is correctly decoded and defects in this process cause devastating human diseases. While basic mechanisms of RQC have been recently defined for cytosolic proteins, almost nothing is known about RQC for ribosomes at the endoplasmic reticulum (ER) that make the nearly one third of human proteins destined for the secretory pathway. The proposed research leverages innovative technologies to elucidate the RQC mechanism for proteins in the secretory pathway.

PI_NAMEs: KOPITO, RON R (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: ATP phosphohydrolase;Binding;Biochemical;Biogenesis;Cells;Collaborations;Cytoplasm;Cytosol;Data;Defect;Disease;Dislocations;Dissection;Endoplasmic Reticulum;Endoplasmic Reticulum Degradation Pathway;Ensure;experimental study;Foundations;genetic information;Genome;Goals;Human;human disease;Impairment;In Vitro;innovative technologies;insight;Knowledge;Label;Lysine;Membrane;Membrane Proteins;Modification;Molecular;Monitor;multicatalytic endopeptidase complex;Organelles;Outcome;Pathway interactions;Peptides;Play;Process;Protein Biosynthesis;Proteins;proteostasis;proteotoxicity;Publishing;Quality Control;Reader;recruit;Recycling;Research;response;Ribosomal Proteins;Ribosomes;Role;Route;seal;secretory protein;segregation;Structure;System;Testing;Time;time use;Transfer RNA;Ubiquitin;Ubiquitin Like Proteins;ubiquitin-protein ligase;Work

PROJECT_TITLE: The role of UFMylation in ribosome quality control at the ER


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative  This project will uncover how signaling by cytokine and growth factor receptors at the cardiomyocyte plasma membrane is transduced within the cell to promote cardiac hypertrophy and heart failure. Although a number of signaling pathways have established roles in cardiac disease pathogenesis, the mechanisms controlling hypertrophic signal transduction circuitry in the adult cardiac myocyte are ill-defined. We will interrogate the functions of protein S-acylation or palmitoylation, a reversible lipid modification, in spatiotemporal regulation of signaling events downstream of cytokine stimulation in cardiomyocytes that may potentially be leveraged for the development of more targeted strategies to treat cardiac disease.

PI_NAMEs: BRODY, MATTHEW JACOB (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Accounting;Acylation;Adult;age related;Agonist;Angiotensin II;aorta constriction;Apoptosis;Binding;Cardiac;Cardiac Myocytes;Cardiomyopathies;Cause of Death;Cell membrane;Cells;Cessation of life;Complex;Cysteine;cytokine;Cytokine Receptors;Cytokine Signaling;Data;Development;Dilated Cardiomyopathy;Disease;Enzymes;Event;Failure;Fatty Acids;Fibrosis;Gene Deletion;Gene Expression;Genes;Genetic Transcription;Golgi Apparatus;Growth Factor Receptors;Heart;Heart Diseases;Heart failure;Heart Hypertrophy;Homeostasis;Hypertrophy;immune cell infiltrate;in vivo;Infection;Infiltration;Inflammation;Inflammatory;Interleukin-6;Investigation;Ischemia;ischemic injury;JAK1 gene;Janus kinase;Kinetics;Lipids;Macrophage;Mediating;Membrane;Modification;Molecular;Mus;mutant;Myocardial;Myocarditis;novel;novel therapeutics;Nuclear;Nuclear Translocation;Output;overexpression;palmitoylation;paracrine;Pathogenesis;Pathologic;Pathway interactions;Phenotype;Phosphorylation;Phosphotransferases;Post-Translational Protein Processing;pressure;Profibrotic signal;programs;protein function;Protein Kinase;Protein S;protein transport;Proteins;Proteomics;receptor;Receptor Signaling;recruit;Regulation;response;Role;Sarcolemma;Signal Induction;Signal Pathway;Signal Transduction;spatiotemporal;Specific qualifier value;STAT protein;Stimulus;Stress;Testing;Time;trafficking;Transcriptional Regulation;Transferase;Transgenic Mice;Transgenic Organisms;United States

PROJECT_TITLE: S-acylation-dependent regulation of cytokine receptor signaling and cardiac maladaptation


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: PITTSBURGH

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Vascular cognitive impairment and dementia (VCID) is a devastating disorder with no effective treatments available to alleviate VCID-related white matter injury and cognitive dysfunction. Vascular insufficiency due to metabolic dysregulation is a potential modifiable factor in VCID pathogenesis. The proposed study will explore adiponectin, a cytokine produced by adipocytes, as a promising therapeutic target for white matter protection and cognitive improvement. We will investigate whether and how activation of adiponectin receptor in VCID brain promotes cerebrovascular autoregulation and strengthens the blood-brain barrier, thereby improving white matter integrity and long-term cognitive outcomes. This information will be valuable for future development of new therapy for VCID and, possibly, other cerebrovascular disease.

PI_NAMEs: CHEN, JUN ;HU, XIAOMING  (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: 3-Dimensional;Accounting;Adipocytes;adipokines;adiponectin;Agonist;Alzheimer's Disease;arteriole;Attention;Attenuated;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood Circulation;Blood Vessels;blood-brain barrier penetration;Brain;brain cell;Carotid Stenosis;Cerebral cortex;cerebral hypoperfusion;Cerebrospinal Fluid;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;chemokine;Chronic;Cognitive;Cognitive deficits;cognitive function;Common carotid artery;cytokine;Data;Dementia;deprivation;Development;Diffusion Magnetic Resonance Imaging;Disease;effective therapy;Electrophysiology (science);Endothelial Cells;endothelial dysfunction;Endothelium;Etiology;Event;Exhibits;Extravasation;fatty acid oxidation;Functional disorder;Future;Glucose;glucose metabolism;Heat-Shock Proteins 90;Homeostasis;hypoperfusion;immune cell infiltrate;Impaired cognition;improved;In Vitro;in vivo;in vivo Model;Incidence;Inflammation;Inflammatory;Inflammatory Response;Injury;Intraperitoneal Injections;Knock-out;Knockout Mice;Lesion;Meta-Analysis;Metabolic;Metabolic dysfunction;Modeling;Mood Disorders;mouse model;Mus;Nervous System Physiology;neuroinflammation;Nitric Oxide;North America;NOS3 gene;novel;novel strategies;novel therapeutics;old mice;Outcome;Oxygen;Pathogenesis;Pathologic;Pathology;Patients;Peripheral;Plasma;Play;Population;Predisposition;Preparation;preservation;Production;prophylactic;receptor;Regimen;Regulation;Reporting;Role;sex;single-cell RNA sequencing;small molecule;Stroke;System;Testing;Therapeutic Effect;therapeutic target;Treatment Protocols;Vascular blood supply;vascular cognitive impairment and dementia;Vascular Dementia;white matter;white matter damage;white matter injury;Wild Type Mouse;young adult

PROJECT_TITLE: Adiponectin on cerebrovascular regulation in vascular cognitive impairment and dementia (VCID)


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Clinical Research;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE We will develop an efficient method to map how mutations to HIV’s envelope protein affect the virus’s sensitivity to antibodies and sera. This work will aid in characterizing immunity to this medically important virus, and will help inform the design of vaccines and therapeutics.

PI_NAMEs: BLOOM, JESSE D (contact)

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: Academy;Address;Affect;Algorithms;Amino Acids;Animals;Antibodies;Bar Codes;Big Data;Biological Assay;Communities;Computer software;computerized tools;cost;Critiques;Data;Data Set;deep sequencing;design;env Gene Products;Enzyme-Linked Immunosorbent Assay;Escape Mutant;Evolution;experimental study;Goals;HIV;HIV Antibodies;HIV envelope protein;HIV vaccine;Human;Immune;Immunity;improved;Intuition;Libraries;Maps;Medical;Medicine;Membrane Proteins;Methods;Modernization;Monoclonal Antibodies;mutant;Mutation;neutralizing antibody;open source;Plasma;pressure;programs;prophylactic;Rabies Vaccines;Research;Research Personnel;Resolution;response;Serum;Site;Structure;Techniques;Therapeutic;tool;Vaccinated;Vaccine Design;vaccine development;vaccine evaluation;vaccine strategy;vaccine-induced antibodies;Vaccines;vaccinology;Viral;Viral Proteins;Virus;Visualization;web platform;Work

PROJECT_TITLE: Complete mapping of immune selection from antibodies to HIV

STUDY_SECTION: VACC

STUDY_SECTION_NAME: HIV/AIDS Vaccines Study Section[VACC]


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE The integrative stress response is an evolutionary conserved pathway to allows cells to react to various stress stimuli to restore cellular homeostasis. We found that the activation of this process in neurons leads to the secretion of a protein fragment that enhances the resilience of surrounding cells to cell stress. We propose to study how this signaling molecule is generated and secreted from neurons in response to stress, how it affects recipient neurons, and how its activity is coordinated with transcriptional programs to facilitate cell survival.

PI_NAMEs: HENGST, ULRICH  (contact)

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Affect;arm;axon growth;Binding;biological adaptation to stress;C-terminal;Caenorhabditis elegans;cell assembly;Cell secretion;Cell Survival;Cells;Cellular Stress;Central Nervous System;ChIP-seq;Chondrocytes;chromatin immunoprecipitation;Cognition Disorders;Communication;Complex;Conditioned Culture Media;Data;deprivation;Endoplasmic Reticulum;endoplasmic reticulum stress;Environment;Exhibits;Exposure to;extracellular;Extracellular Space;Genetic Transcription;Glucose;Homeostasis;improved;In Vitro;in vivo;intercellular communication;Knockout Mice;Link;Malignant Neoplasms;Mediating;Mediator;Membrane;Mitochondria;Mitochondrial Proteins;Modality;Molecular;N-terminal;nanomolar;Nerve Degeneration;Nervous System;Neurodegenerative Disorders;Neurons;neuroprotection;neurotransmission;novel;overexpression;Oxidative Stress;Oxidative Stress Induction;paracrine;Paracrine Communication;Pathway interactions;Process;Production;programs;promote resilience;Proteasome Inhibition;Protein Fragment;Proteins;Rattus;Reaction;Reactive Oxygen Species;receptor;Reporting;Research Project Grants;resilience;response;Role;SHH gene;Signal Pathway;Signal Transduction;Signaling Molecule;smoothened signaling pathway;SOD2 gene;Stimulus;Stress;stressor;Testing;transcription factor;transcriptome sequencing;transmission process;Work

PROJECT_TITLE: Neuroprotection by a Secreted Component of the Cellular Stress Response

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


NIH_SPENDING_CATS: Genetics;Networking and Information Technology R&D (NITRD)

ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

ORG_STATE: MA

PHR: Narrative  Many approaches exist to predict RNA structures so that function can be better understood, but generally they tend to be biased towards any sequence having a structure of some sort. We will create a web-based platform that will reliably assess the existence of a conserved RNA structure and propose such a structure with high accuracy, using evolutionary as well as RNA structure information. Integrating existing but not widely adopted computational methods into a webserver that will take a single RNA sequence as input will enable its extensive use throughout the community so that RNA research can continue thriving in new directions.

PI_NAMEs: RIVAS, ELENA  (contact);VICENS, QUENTIN

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: Adopted;Adoption;Algorithms;Biological;Biology;Cells;Communities;comparative;Computational Biology;Computer software;computerized tools;Computing Methodologies;cost;Development;Evaluation;Evolution;Experimental Designs;Family;Free Energy;Genome;Goals;Homologous Gene;improved;interest;Knowledge;Link;Maps;Methods;Modeling;novel;Organism;Outcome;Output;Phylogenetic Analysis;prediction algorithm;predictive tools;programs;protein structure prediction;Research;Retrieval;RNA;RNA Sequences;Running;Science;Sequence Alignment;Sequence Homologs;Site-Directed Mutagenesis;Sorting;structural biology;Structure;Techniques;Technology;therapeutic RNA;Time;tool;transcriptome;Validation;Variant;wasting;web platform;web server;Work

PROJECT_TITLE: An all-in-one web server for RNA structure prediction using evolutionary information

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE Kentucky ranks highest in rates of overall cancer incidence and mortality [1]. To address this major health issue, the University of Kentucky Center of Biomedical Research Excellence on Cancer and Metabolism will sustain a robust infrastructure to continue to conduct basic and translational research to better define the metabolic dysregulations governing tumor development, metastasis, drug resistance and recurrence. This will be achieved through the cultivation and expansion of a cadre of promising project leaders by providing research support, mentoring and access to state-of-the-art metabolic and imaging core facilities.

PI_NAMEs: ZHOU, BINHUA P (contact)

PROGRAM_OFFICER_NAME: REVILLEZA, MARIA

PROJECT_TERMS: Address;animal imaging;anti-cancer research;Applications Grants;Area;base;Basic Science;Biochemistry;Bioinformatics;Biology;biomarker identification;Biometry;cancer cell;Cancer Center;cancer imaging;cancer initiation;cancer prevention;cancer therapy;career;Cell Survival;Centers of Research Excellence;Clinical;Clinical Trials;Collaborations;Core Facility;Coupled;Data;Dedications;defined contribution;Development;Disease;Distant Metastasis;Drug resistance;Early Diagnosis;editorial;Educational workshop;Environment;Epigenetic Process;Equipment;Extramural Activities;Faculty;Fees;Fostering;Foundations;Funding;Goals;Grant;Growth;Health;Image;improved;in vivo;Incidence;Infrastructure;innovation;Institution;Interdisciplinary Study;Intervention;Kentucky;Link;Malignant Neoplasms;Mediator;Mentors;Metabolic;Metabolic Diseases;Metabolism;metabolomics;Methodology;mortality;multidisciplinary;Neoplasm Metastasis;new technology;next generation;novel;Obesity;Outcome;Oxidation-Reduction;Phase;Pilot Projects;Positioning Attribute;prevent;Productivity;programs;Protein Array;Quality of life;recruit;Recurrence;Research;Research Personnel;Research Project Grants;Research Support;Role;Scientist;Services;Signal Transduction;skills;success;symposium;synergism;System;Therapeutic;therapeutic target;therapy resistant;tool;Training;Translational Research;Translations;tumor;tumor initiation;tumor metabolism;tumorigenesis;United States National Institutes of Health;Universities;Vital capacity

PROJECT_TITLE: University of Kentucky Center for Cancer Metabolism


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cancer

PROJECT_TERMS: Accountability;Address;Administrative Efficiency;Administrator;Advanced Malignant Neoplasm;Advisory Committees;anti-cancer research;Area;Biochemistry;Bioinformatics;biomedical informatics;Biomedical Research;Biometry;Cancer Center;cancer therapy;Cardiovascular Diseases;career development;Centers of Research Excellence;Clinical;clinical center;Clinical Sciences;Communication;Communication Programs;Coupled;Data;Data Science;Death Rate;Dedications;Development;Disparate;Effectiveness;Ensure;Evaluation;Faculty;flexibility;Fostering;Goals;Health;imaging capabilities;improved;Incidence;Informatics;Infrastructure;innovation;Kentucky;Knowledge;Leadership;Malignant Neoplasms;Mediator;meetings;Mentors;Mentorship;Metabolic;Metabolism;metabolomics;Molecular Medicine;Monitor;multidisciplinary;National Cancer Institute;next generation;novel;Obesity;Oncogenic;Pharmacologic Substance;Pilot Projects;Play;Process;Productivity;Program Evaluation;programs;Research;Research Infrastructure;Research Personnel;Research Training;Resource Sharing;Resources;Role;Scientist;Seasons;Senior Scientist;Services;skills;Structure;success;synergism;System;therapeutic target;tool;Translational Research;tumor metabolism;Universities;Vision

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Cancer

PI_NAMEs: LANE, ANDREW N. (contact)

PROJECT_TERMS: Address;advanced analytics;Algorithms;analytical method;Behavior;Biochemical;Biochemistry;Bioinformatics Shared Resource;Biological;Biology;Biomass;Biometry;Cancer Center;Carbon;cell growth;Cells;Centers of Research Excellence;Chromatography;Classification;Collaborations;Consult;Culture Media;Data;data acquisition;Data Analyses;data reduction;Databases;Development;Dinucleoside Phosphates;Disease;Electrophoresis;Experimental Designs;Fourier Transform;Genomics;Goals;high throughput analysis;Human Resources;Inductively Coupled Plasma Mass Spectrometry;Informatics;Infusion procedures;Isotope Labeling;Isotopes;Kentucky;Liquid Chromatography;Literature;Logistic Regressions;Malignant Neoplasms;Mass Spectrum Analysis;medical specialties;Metabolic;metabolic abnormality assessment;Metabolic Pathway;Metabolism;metabolome;metabolomics;Methods;Mus;Nuclear Magnetic Resonance;Operative Surgical Procedures;Organism;Output;Oxidation-Reduction;Pathway Analysis;Phase;Preparation;Principal Investigator;Procedures;Process;Protein Analysis;Protein Array;Proteins;Research Personnel;Resolution;Retrieval;Sampling;Schedule;Services;Source;stable isotope;Standardization;Statistical Data Interpretation;System;Techniques;Technology;Time;Tissue Harvesting;Tissues;Trace Elements;Tracer;tumor metabolism;ultra high resolution;Universities;Update;Validation;web site

PROJECT_TITLE: Metabolism Core


NIH_SPENDING_CATS: Biomedical Imaging;Building Research Capacity at Institutions with Limited NIH Funding;Cancer

PI_NAMEs: JIA, JIANHANG  (contact)

PROJECT_TERMS: advanced analytics;Advanced Malignant Neoplasm;Aging;analytical tool;Animal Disease Models;animal facility;anti-cancer research;Area;Award;Bioinformatics;Bioluminescence;Biomedical Research;Biometry;Cancer Center;cancer therapy;cell motility;Centers of Research Excellence;Clinical;Complex;Computer software;Consult;Consultations;cost effective;Data;Dedications;design;Development;digital;Disease Progression;Distant;Equipment;Evaluation;Experimental Designs;Extramural Activities;Faculty;flexibility;Floor;Fluorescence;Goals;Human Resources;Image;imaging capabilities;Imaging Device;imaging modality;imaging study;imaging system;Imaging Techniques;in vivo;in vivo imaging;in vivo imaging system;Individual;Infrastructure;instrument;Kentucky;Laboratories;Laboratory Research;Link;Malignant Neoplasms;Medicine;Metabolic;Metabolism;metabolomics;Methodology;Methods;Microscope;Mission;Monitor;multidisciplinary;Mus;National Institute of General Medical Sciences;Neoplasm Metastasis;novel;optical imaging;Organ;Pathology;Phase;Pilot Projects;Positioning Attribute;Productivity;programs;Proteins;Research;Research Infrastructure;Research Personnel;Research Project Grants;Research Support;Resources;Role;Sampling;Scientist;Services;Site;skills;Slide;success;System;Tissues;Training;Transfection;treatment response;tumor initiation;tumor metabolism;tumorigenesis;Universities;Work

PROJECT_TITLE: Imaging Core


NIH_SPENDING_CATS: Biotechnology;Congenital Structural Anomalies;Genetics;Human Genome;Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SAN FRANCISCO

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Narrative Azoles are common antifungal agents widely-used in clinical applications and agriculture. In vertebrates, exposures to azoles during early embryonic development results in developmental toxicity outcomes, including, craniofacial and axial defects. In this study, we aim to delineate mechanisms underlying azole-induced developmental toxicity utilizing single cell transcriptomic-based approaches, gene-editing tools, and established alternative model systems of early embryonic development.

PI_NAMEs: ROBINSON, JOSHUA FREDERICK (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: adverse outcome;Agriculture;Animals;anti-fungal agents;Azoles;Biological Availability;Biological Models;Branchial arch structure;Cell Differentiation process;Cell Lineage;Cell Proliferation;Cell Wall;Cells;Chemical Exposure;Chemicals;Classification;clinical application;Congenital Abnormality;craniofacial;CRISPR/Cas technology;Custom;Cytochrome P450;Data;data integration;Data Set;Defect;Dermal;design;Development;developmental toxicity;developmental toxicology;differential expression;Dysmorphology;Embryo;embryo cell;embryo culture;Embryonic Development;Endocrine;environmental chemical;enzyme pathway;Event;Exposure to;flusilazole;gene editing technology;Gene Expression;Genes;Genetic;genetic signature;Genetic Transcription;genome editing;Goals;hazard;Health;hindbrain;Homeobox Genes;Human;human embryonic stem cell;Impairment;in silico;In Vitro;innovation;insight;Intravenous;Investigation;Laboratories;Libraries;Ligands;Link;Lipids;malformation;Maps;Medicine;Metabolism;Modeling;Molecular;molecular phenotype;Molecular Target;Morphology;nerve stem cell;neural;Neural Tube Development;novel;Nuclear;Oral;Organism;Organogenesis;Outcome;Pathway interactions;Pattern;Phenotype;Predisposition;Pregnancy;Pregnant Women;Proliferating;Rattus;Risk;RNA;Rodent;Role;Route;Safety;Signal Pathway;Signal Transduction;single-cell RNA sequencing;spatiotemporal;stem cell model;steroid metabolism;Sterols;System;Teratogens;Testing;Time;tool;Toxic effect;Toxicity Tests;Toxicogenomics;Toxicology;transcriptome;transcriptome sequencing;transcriptomics;Tretinoin;Validation;Vertebrates;Zebrafish

PROJECT_TITLE: Delineating mechanisms underlying azole-induced developmental toxicity using single cell transcriptomic approaches, genome editing tools, and alternative models


NIH_SPENDING_CATS: Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Comparative Effectiveness Research;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Machine Learning and Artificial Intelligence;Mental Health;Mental Illness;Patient Safety;Physical Injury - Accidents and Adverse Effects;Post-Traumatic Stress Disorder (PTSD);Serious Mental Illness;Social Determinants of Health;Suicide;Violence Research

ORG_CITY: ALBUQUERQUE

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: PROJECT NARRATIVE Post-traumatic stress disorder (PTSD), and its associated conditions (e.g., traumatic brain injury and suicidality) are often underdiagnosed, and have outcomes that are difficult to predict. Treatment of PTSD often involves frequent treatment changes with multi-drug regimens (polypharmacy) and off-label medications for which the relative risks and benefits are largely unknown. To address these problems, we will develop and apply methods to identify undiagnosed patients, predict disease trajectories, and compare the effectiveness of all common PTSD treatments using health records from millions of patients in Veterans Administration (VA) and non-VA databases.

PI_NAMEs: LAMBERT, CHRISTOPHE G. (contact)

PROGRAM_OFFICER_NAME: LUSHIN, VICTOR

PROJECT_TERMS: Accounting;Address;Affect;Aftercare;Behavior;Benefits and Risks;Bipolar Disorder;causal model;Cause of Death;Clinical;Code;comorbidity;comparative effectiveness;Comparative Effectiveness Research;comparative effectiveness study;compare effectiveness;Complex;Data;Data Science;Data Set;Databases;Decision Making;Department of Defense;Detection;Diagnosis;Diagnostic;Disease;disease model;Disease Outcome;Disease Progression;Disparity;Documentation;Drug Combinations;effective therapy;Electronic Health Record;Ethnic Origin;experience;Fostering;Funding;General Population;Goals;health care disparity;health data;health disparity;health record;Healthcare;high risk;Hospitalization;Human Resources;improved;Informatics;inpatient psychiatric treatment;International;Intervention;Investigation;Label;Learning;learning strategy;Machine Learning;Major Depressive Disorder;Medical;Mental Depression;Mental disorders;Mental Health;Methods;Military Personnel;model development;Modeling;multidisciplinary;multiple drug use;neglect;novel;off-label drug;Outcome;Patient Care;Patient-Focused Outcomes;Patients;Persons;Pharmaceutical Preparations;Pharmacological Treatment;Pharmacotherapy;Phenotype;Polypharmacy;Population;Positioning Attribute;Post-Traumatic Stress Disorders;Prognosis;Protocols documentation;psychosocial;Psychotherapy;Race;Recovery;Regimen;Relative Risks;Research;Research Design;research study;Resources;response;Risk;Risk Assessment;Schizophrenia;Self-Injurious Behavior;service delivery;sex disparity;Sleep Disorders;sociodemographic factors;Socioeconomic Factors;Substance Use Disorder;success;suicidal;suicidal act;suicide rate;Survival Analysis;symptomatic improvement;tertiary prevention;therapy design;Thinking;Time;trauma exposure;Traumatic Brain Injury;treatment choice;treatment comparison;Treatment outcome;Treatment Protocols;United States Department of Veterans Affairs;Veterans;Veterans Health Administration

PROJECT_TITLE: Deriving high-quality evidence from national healthcare databases to improve suicidality detection and treatment outcomes in PTSD

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Genetics;Human Genome;Prostate Cancer;Urologic Diseases

PI_NAMEs: FONG, KA-WING  (contact);ST CLAIR, DARET K

PROJECT_TERMS: advanced prostate cancer;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;Androgens;Binding;Cancer Center;Cancer Etiology;Cells;Cessation of life;Clinical;Complex;Consumption;Data;Deposition;Development;Disease;DNA;Enzymes;Epigenetic Process;epigenetic silencing;gene repression;Genes;genetic corepressor;genetic signature;Genetic Transcription;genomic locus;Genomics;Growth;Histone H3;inhibitor;Kentucky;knock-down;Lysine;Malignant neoplasm of prostate;Mediating;men;Metabolic;Metabolic Pathway;Metastatic Prostate Cancer;Methyltransferase;Molecular;new therapeutic target;novel;Oncogenic;Outcome;overexpression;Pathway interactions;prostate cancer cell;Prostate Cancer therapy;Receptor Activation;SETDB1 gene;steroid hormone;sugar;targeted treatment;Testing;transcription factor;tumor metabolism;Universities

PROJECT_TITLE: TRIM28 fuels prostate cancer growth through SETDB1-mediated epigenetic silencing of androgen metabolic genes UGT2B15 and UGT2B17


NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Clinical Research;Data Science;Heart Disease;Heart Disease - Coronary Heart Disease;Machine Learning and Artificial Intelligence

PHR: PROJECT NARRATIVE This translational research applies cutting-edge bioengineering techniques to better understand and characterize the mechanisms of ventricular arrhythmias, which remain the most common cause of sudden death in patients with heart failure. Novel analysis of the interplay between structural and electrical abnormalities of the heart will provide actionable classifications of ventricular arrhythmia substrate for therapy and future study.

PI_NAMEs: ROGERS, ALBERT JOSEPH (contact)

PROGRAM_OFFICER_NAME: WEBB, STEPHANIE JOHNSON

PROJECT_TERMS: Ablation;Acceleration;Action Potentials;Acute;Anti-Arrhythmia Agents;Area;Arrhythmia;arrhythmogenic cardiomyopathy;Biomedical Engineering;Cardiac;Cardiac ablation;Cardiomyopathies;Cause of Death;Cell Physiology;Cessation of life;Cicatrix;Classification;Classification Scheme;Clinical;clinical decision-making;clinical training;clinical translation;Communication;Coronary Arteriosclerosis;Coronary artery;Data;Data Analyses;Data Science;Databases;density;Diagnosis;Disease;Electrophysiology (science);Engineering;Enrollment;Etiology;Fellowship;Fibrosis;Fingerprint;Foundations;Functional disorder;Future;Gadolinium;Goals;Growth;Heart;Heart Abnormalities;Heart Atrium;Heart failure;Image;imaging study;Implantable Defibrillators;improved;in vivo;indexing;innovation;Intervention;Ischemia;Knowledge;Label;Link;Machine Learning;machine learning model;Magnetic Resonance Imaging;Maps;Measurement;Measures;Medicine;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methods;Modeling;multimodal data;multimodality;Myocardial;Myocardial Ischemia;Myocardium;National Heart, Lung, and Blood Institute;Network-based;neural network;novel;novel therapeutics;Outcome;patient registry;patient response;patient stratification;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Physiological;porcine model;predict clinical outcome;Prevention;Procedures;programs;Recurrence;Refractory;Research;Research Infrastructure;Resources;response;Risk;Risk Assessment;Scientist;Signal Transduction;skills;spatial relationship;Structural defect;Sudden Death;supportive environment;targeted treatment;Techniques;Therapeutic;Therapeutic Intervention;Time;tool;Training;Translating;Translational Research;Translations;treatment response;United States;United States National Institutes of Health;Ventricular;Ventricular Arrhythmia;Ventricular Fibrillation;voltage;Writing

PROJECT_TITLE: Electrical Mapping Signatures of Adverse Structural and Functional Remodeling in Ventricular Arrhythmia

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(OA)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: CHAPEL HILL

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: NARRATIVE Cancers of children and young adults result from the interplay between genetic and epigenetic factors and the cellular states that accompany a period of developmental progression and accelerated growth. We propose a project that explore this relationship through the bone and soft tissue cancer Ewing sarcoma. How the critical oncoprotein that leads to Ewing sarcoma influences and is itself influenced by an evolving chromatin environment will be studied.

PI_NAMEs: DAVIS, IAN J (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Acceleration;Adolescent;Adolescent and Young Adult;Binding;Biochemical;Biological Models;Bone Tissue;cancer cell;Cell Differentiation process;Cell Physiology;Cell Proliferation;Cells;Characteristics;chemotherapy;Child;Chimeric Proteins;Chromatin;Chromosomal Rearrangement;Chromosomal translocation;cofactor;Common Neoplasm;CRISPR interference;Dependence;Development;differentiation in vitro;embryonic stem cell;Enabling Factors;Enhancers;Environment;Epigenetic Process;epigenomics;ETS Domain;Ewings sarcoma;EWS-FLI1 fusion protein;EWSR1 gene;Family member;FLI1 gene;Fostering;Fusion Oncogene Proteins;Generations;Genes;Genetic;Genetic Transcription;Genomics;Growth;Heterogeneity;Histologic;histone modification;Histones;Human;hybrid gene;Impact evaluation;insight;Label;Link;Malignant Bone Neoplasm;Malignant Childhood Neoplasm;Malignant Neoplasms;Mass Spectrum Analysis;Mediator;Mesenchymal Cell Neoplasm;Mesenchymal Differentiation;Mesenchymal Stem Cells;Microsatellite Repeats;neoplastic cell;new therapeutic target;novel;novel strategies;Oncogenic;Oncoproteins;Operative Surgical Procedures;patient - derived stem cells;patient derived induced pluripotent stem cells;PAX7 gene;permissiveness;Pluripotent Stem Cells;Post-Translational Protein Processing;Process;Proliferating;protein function;Proteins;Proteomics;Radiation;recruit;Regulation;Regulatory Pathway;Research Personnel;RNA;Sarcoma;Site;small hairpin RNA;soft tissue;stem cell differentiation;stem cell model;stem cells;Testing;transcription factor;transcriptome;transcriptomics;tumor;Untranslated RNA;Variant;Work;young adult

PROJECT_TITLE: Developmental control of chromatin states in cancer

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Neuroblastoma;Neurosciences;Pediatric;Pediatric Cancer;Rare Diseases

PI_NAMEs: RELLINGER, ERIC JAMES (contact);ST CLAIR, DARET K

PROJECT_TERMS: 3-Dimensional;angiogenesis;Cancer Cell Growth;Cancer Center;Cell Survival;Cephalic;CRISPR/Cas technology;Dropout;Glutamine;high risk;In Vitro;in vivo;inhibitor;Kentucky;Knock-out;Malignant Neoplasms;Metabolic;Metabolic Pathway;Metabolism;metabolomics;MYCN gene;Neoplasm Metastasis;Neuroblastoma;neuroblastoma cell;Organoids;Patients;Pediatric Neoplasm;Primary Neoplasm;Proto-Oncogenes;Role;small molecule;Solid Neoplasm;stable isotope;subcutaneous;tumor growth;tumor metabolism;Universities;uptake;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Targeting Glutamine Uptake via ASCT2 Inhibition in MYCN-amplified Neuroblastomas


ED_INST_TYPE: UNIVERSITY-WIDE

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

ORG_STATE: NY

PHR: NARRATIVE This proposal aims to apply innovative multimodal MRI approaches to evaluate the therapeutic effects of the combined therapy of hydrogen water and minocycline treatment on ischemic stroke in the established middle cerebral artery occlusion model in rats. These integrated approaches are expected to provide a comprehensive anatomical, physiological and functional profile of ischemic tissue at risk and their spatiotemporal characteristics and how the treatment reduces ischemic injury. These findings have the potential to lead to novel effective treatment of ischemic stroke during the acute and chronic phase, and enhance clinical decision making in the treatment of acute stroke.

PI_NAMEs: DUONG, TIMOTHY Q. (contact);MUIR, ERIC RAYMOND

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Acute;acute stroke;Address;Alteplase;Ambulances;Anatomy;Animals;Anti-Inflammatory Agents;Antioxidants;Apoptosis;Autophagocytosis;behavior test;Behavioral;behavioral outcome;Blood Vessels;Brain;Brain Ischemia;Cause of Death;Cell-Mediated Cytolysis;cerebrovascular reactivity;Cerebrum;Characteristics;Chronic Phase;chronic stroke;Classification;clinical decision-making;Clinical Trials;Combined Modality Therapy;comparative efficacy;cytotoxicity;Data;Development;Diffusion;dosage;Dose;Double-Blind Method;effective therapy;efficacy evaluation;Evolution;Experimental Designs;Failure;FDA approved;Free Radicals;functional status;gray matter;Health;Histologic;Histology;Hour;Human;Hydrogen;improved;in vivo;Individual;Infarction;Inflammation;Injury;innovation;Ischemia;ischemic injury;Ischemic Stroke;Lesion;Long term disability;Magnetic Resonance Imaging;Measures;Metabolic;Methods;Middle Cerebral Artery Occlusion;Minocycline;Modeling;molecular hydrogen;multimodality;Multiple Trauma;Nervous System Disorder;Neurologic;neuroprotection;novel;novel therapeutic intervention;Operative Surgical Procedures;Pathway interactions;Perfusion;Phase;Physiological;post stroke;prevent;Quality of life;Randomized;Rattus;Recovery of Function;Reperfusion Therapy;response;Risk;Safety;spatiotemporal;Stroke;stroke clinical trials;stroke model;stroke patient;stroke therapy;Therapeutic Effect;Thrombolytic Therapy;Time;Tissue Viability;Tissues;Treatment outcome;Water;water treatment;white matter;white matter damage;Work

PROJECT_TITLE: MRI Study of Hydrogen Water and Minocycline Combination Therapy for Ischemic Stroke


NIH_SPENDING_CATS: Biotechnology;Climate-Related Exposures and Conditions;Digestive Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Social Determinants of Health

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Relevance to Public Health Air pollution exacerbates inflammation and is a significant contributor to the development of chronic inflammatory diseases. Emerging scientific evidence suggests that air pollution mitigates pathways involved in the resolution of inflammation leading to chronic inflammatory diseases including atherosclerosis and IBD. Successful completion of work proposed in this application, i) will identify novel molecular mechanisms that regulate resolution of inflammation and ii) will provide novel therapeutic strategies for, the treatment of chronic inflammatory diseases including atherosclerosis and IBD, exacerbated by environmental exposures.

PI_NAMEs: REDDY, SRINIVASA T. (contact)

PROGRAM_OFFICER_NAME: NADADUR, SRIKANTH

PROJECT_TERMS: Acute;Affect;Air Pollutants;Air Pollution;Alzheimer's Disease;analog;Anti-Inflammatory Agents;Antioxidants;Apolipoprotein A-I;Arachidonic Acids;Aromatic Polycyclic Hydrocarbons;Atherosclerosis;Attenuated;Biological;Biology;Cells;Cholates;Chronic;Chronic Disease;chronic inflammatory disease;Chronic Obstructive Pulmonary Disease;Circulation;Development;Diabetes Mellitus;Diesel Exhaust;dietary;Disease;disease model;Eicosanoids;Environmental Exposure;Environmental Pollutants;Enzymes;Epithelium;Equilibrium;experimental study;Exposure to;Fatty acid glycerol esters;fighting;gut inflammation;High Fat Diet;Homeostasis;immunoregulation;Impairment;improved;in vivo;Infection;Inflammation;Inflammation Mediators;Inflammatory;intestinal barrier;intestinal epithelium;Intestines;Knock-out;Knockout Mice;Knowledge;Laboratories;Lesion;lipid mediator;lipid metabolism;lipid transport;Lipids;lipoxin A4;Macrophage;Malignant Neoplasms;Mediating;Mediator;Molecular;Mus;Myelogenous;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Obesity;Organoids;Oxidative Stress;Parkinson Disease;particle;Pathway interactions;peptide L;peptidomimetics;Phenotype;Physiological Processes;Play;Production;Property;Prostaglandins;PTGS2 gene;Public Health;Publishing;Recovery;repaired;Reporting;Research;Resolution;response to injury;Role;Small Intestines;Testing;tissue repair;Tissues;Toxic effect;Toxic Environmental Substances;ultrafine particle;Work

PROJECT_TITLE: Novel Approaches for Improving Inflammation Resolution Following Chronic Exposure to Air Pollutants


ED_INST_TYPE: SCHOOLS OF PHARMACY

PHR: Taxane-induced peripheral neuropathy (TIPN) is an irreversible, life-altering side effect of taxane chemotherapy that cannot be prevented or treated, and therefore requires premature discontinuation of taxane treatment in many patients. The proposed research is highly relevant to the NCI mission because it will validate clinically-useful and mechanistically informative predictive TIPN biomarkers and develop an Integrated TIPN Prediction Model. This work will enable the study team to develop biomarker-informed interventions that positively impact patients’ quantity and quality of life by preventing TIPN and enhancing taxane treatment effectiveness.

PI_NAMEs: HERTZ, DANIEL LOUIS (contact);TRIVEDI, MEGHNA S

PROGRAM_OFFICER_NAME: FILIPSKI, KELLY

PROJECT_TERMS: Activities of Daily Living;Age;Amino Acids;Antineoplastic Agents;Biological Markers;Breast;candidate marker;Carcinogens;chemotherapy;Clinical;clinical practice;Clinical Practice Guideline;Clinical Research;Clinical Trials;cohort;Data;Development;Diet;DNA;docetaxel;Dose;experience;Funding;Generations;Genes;Genetic;Genetic Markers;genome-wide;genomic data;Genotype;Germ Lines;Goals;hereditary neuropathy;Histidine;improved;individual patient;insight;Intervention;Knowledge;Life;lifestyle factors;Link;lipidomics;Lipids;Lung;Machine Learning;Malignant Neoplasms;Manuals;Measures;Mission;Neuropathy;novel;Nutrient;Outcome;Outcomes Research;Ovarian;Paclitaxel;Patients;Peripheral Nervous System Diseases;Pharmaceutical Preparations;Phospholipids;Physiological;Plasma;predictive marker;predictive modeling;Predictive Value;premature;prevent;Prevention;Prevention strategy;preventive intervention;Process;prospective;Quality of life;Race;Recommendation;Research;Risk;risk prediction;risk prediction model;Sampling;side effect;Southwest Oncology Group;Sphingomyelins;taxane;Testing;Translating;Treatment Effectiveness;Treatment outcome;treatment strategy;tumor;United States;Variant;Vitamin D;Vitamins;Work

PROJECT_TITLE: Development of an Integrated Risk Prediction Model of Taxane-induced Peripheral Neuropathy

STUDY_SECTION: XNDA

STUDY_SECTION_NAME: Xenobiotic and Nutrient Disposition and Action Study Section[XNDA]