NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Genetics;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: AMHERST

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

ORG_STATE: NY

PHR: PROJECT NARRATIVE Heroin abuse and addiction has become an epidemic health challenge, yet there continues to be a poor understanding of the molecular events that lead to the “addicted brain.” This application explores the contribution of the actin regulator drebrin in mediating behavioral, cellular, and morphological plasticity following heroin taking. The proposed research is relevant to the part of NIH's mission that may identify novel pharmacotherapies to combat opioid addiction.

PI_NAMEs: DIETZ, DAVID M (contact)

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Abstinence;Actin-Binding Protein;Actins;addiction;Addictive Behavior;Attenuated;Behavior;Behavioral;behavioral plasticity;Binding;Biological Process;Brain;Brain region;cell type;Cells;Chronic;combat;Cues;Data;Dendritic Spines;Dependence;Development;Disease;Dopamine D2 Receptor;Down-Regulation;drebrins;drug abstinence;Drug Addiction;drug craving;drug relapse;effective intervention;effective therapy;Epidemic;Epigenetic Process;Event;experimental study;Functional disorder;G Actin;gene therapy;Goals;Health;Heroin;Heroin Abuse;Heroin Dependence;Homeostasis;Incubated;Induced Neurons;inducible Cre;Intervention;Intravenous;knock-down;Measures;Mediating;Messenger RNA;MicroRNAs;Mission;Modeling;Molecular;Morphology;National Institute of Drug Abuse;neural;neuroadaptation;neurobiological mechanism;Neurobiology;Neuronal Plasticity;Neurons;novel;novel therapeutics;Nucleus Accumbens;Open Reading Frames;Opiate Addiction;Opioid;opioid use;Overdose;overexpression;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Population;Predisposition;prescription opioid misuse;Process;Proteins;Rat Transgene;Rattus;Recurrent disease;Regulation;Relapse;relapse prevention;Research;response;Rewards;Role;Self Administration;Specificity;substance abuse treatment;Substance Addiction;Synapses;Testing;Therapeutic;Time;Transcriptional Regulation;United States National Institutes of Health;Viral Genes;virtual;Virus;Work

PROJECT_TITLE: Heroin-induced plasticity: the role of actin dynamics

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: Boulder

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Ionizing radiation is one of the most common treatments used against cancer; however, radioresistance is still a signific clinical problem since cancer cells can survive and regenerate tumors. This proposal aims to understand how cells survive after exposure to radiation to enhance radiotherapy. I aim to understand how cells survive after activating apoptotic caspases, enzymes canonically known as markers of apoptosis.

PI_NAMEs: COLON PLAZA, SARAH IVETTE (contact)

PROGRAM_OFFICER_NAME: STEPANEK, LAURIE ELIZABETH

PROJECT_TERMS: Adult;Apoptosis;Apoptotic;Area;Aspartic Acid;Biosensor;cancer cell;Cancer Patient;Caspase;Cell Death;Cell Survival;Cells;Cessation of life;Clinical;common treatment;Data;Development;DNA;DNA Damage;DNA Maintenance;DNA Repair;DNA Repair Gene;Drosophila genus;Drosophila melanogaster;Dyes;Enzymes;experience;experimental study;Exposure to;fly;Foundations;gene product;Genes;Genetic;genetic inhibitor;genome integrity;Genome Stability;Goals;homologous recombination;Human;improved;Induction of Apoptosis;inhibitor;insight;interest;Ionizing radiation;irradiation;Lead;Learning;Life;Loss of Heterozygosity;Malignant Neoplasms;model organism;Molecular;Natural regeneration;Nonhomologous DNA End Joining;notch protein;Notch Signaling Pathway;novel;Pathway interactions;Pattern;Peptide Hydrolases;pharmacologic;Process;promoter;Proteins;Publishing;Radiation;Radiation exposure;radiation resistance;Radiation therapy;recombinational repair;Regulation;repaired;Research;Roentgen Rays;Role;Signal Pathway;Signal Transduction;Spatial Distribution;Structure;success;Testing;Tissues;Treatment Failure;treatment optimization;Treatment outcome;tumor;tumorigenesis;Vertebrates;Wing;Work

PROJECT_TITLE: Mechanisms that underlie the life/death decisions in a cell that activated apoptotic caspases

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

ORG_CITY: CAMBRIDGE

ORG_DEPT: CHEMISTRY

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: PROJECT NARRATIVE A protein is a gene-encoded string of amino acids that folds into a three-dimensional structure. Proteins perform the molecular functions that are necessary for life, including catalysis of biochemical reactions (by enzymes), neutralization of foreign toxins (by antibodies), and stimulation of cellular activity (by hormones). The goal of this project is to develop chemical means to manipulate proteins with a precision that is unobtainable with other (e.g., genetic) methods and to endow proteins thereby with desirable attributes that could be transformative to many aspects of biomedicine.

PI_NAMEs: RAINES, RONALD T (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TITLE: Protein Chemistry

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Infectious Diseases;Orphan Drug;Prevention;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PI_NAMEs: DITTMER, DIRK P (contact)

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;adaptive immune response;Address;Africa;African American;AIDS Malignancy Consortium;AIDS related cancer;analysis pipeline;Animal Model;Area;Basic Science;biocontainment facility;Bioinformatics;Biological Markers;Biological Products;Biology;Cancer Center Support Grant;cancer therapy;Carcinogens;Catchment Area;Cell secretion;Cells;Clinical;Communities;community engagement;Community Healthcare;Community Outreach;delivery vehicle;demographics;Development;Diagnosis;Direct Costs;Disparity;distinguished professor;Doctor of Philosophy;Endogenous Retroviruses;Environment;Epidemic;Epigenetic Process;epigenome;exosome;extracellular vesicles;Extramural Activities;Faculty;Flowers;Funding;Gene Delivery;gene therapy;Genomics;Goals;Graduate Education;graduate student;Grant;Hispanic Women;HIV;HIV Infections;Home;HPV positive;Human;Human Papilloma Virus Vaccine;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;humanized mouse;Immune signaling;Immunity;Immunology;Immunotherapy;Incidence;Infectious Agent;Innate Immune Response;interest;International Agency for Research on Cancer;Intervention;Investments;Leadership;Lentivirus;Link;malignant mouth neoplasm;Malignant neoplasm of cervix uteri;Malignant Neoplasms;medical schools;member;metabolomics;Microbiology;microbiome analysis;MicroRNAs;Minority;Modernization;Modification;Molecular;National Cancer Advisory Board;NCI-Designated Cancer Center;Neoplasms;neoplastic cell;next generation sequencing;North Carolina;novel;novel therapeutics;Oncogenic Viruses;Oncology;oral HPV-positive head and neck cancers;Organoids;Patients;Pattern;peer;Persons;Pharmaceutical Preparations;Postdoctoral Fellow;pre-clinical;prevent;Prevention;Professional counselor;professor;programs;Proteomics;Publications;Reagent;recruit;Relative Risks;Research;Research Personnel;Research Project Grants;Role;Sampling;Series;Services;Shapes;Signal Pathway;single cell sequencing;single cell technology;small hairpin RNA;small molecule;Specimen;Systems Biology;Training;Training and Education;training opportunity;translational study;tumor;tumorigenesis;United States National Academy of Sciences;United States National Institutes of Health;Vaccines;vector;Viral;Viral Cancer;viral detection;Viral Genome;Viral Pathogenesis;Viral Vector;virology;Virus;virus related cancer;Virus-Cell Membrane Interaction;Vulnerable Populations;White Women;Work

PROJECT_TITLE: Virology Research Program

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Cancer Centers Study Section (A)[NCI-A]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: IOWA CITY

ORG_NAME: IOWA CITY VA MEDICAL CENTER

ORG_STATE: IA

PHR: Type 2 diabetes is the major health problem for US veterans that imposes significant physical, financial, and emotional tolls. The prevalence of Type 2 diabetes is increasing and affects over 20% of veterans, a rate significantly higher than in general civilian population. Strong association of depression with Type 2 diabetes adds to challenges for veterans who suffer from high prevalence of post-traumatic stress disorder. Thus, there is a strong and urgent need for an effective and widely applicable therapy. Excessive accumulation of lipids in beta cells is considered to contribute to the development of Type 2 diabetes. However, it still remains elusive how lipid accumulation and mobilization is regulated in beta cells. The proposal aims to increase our understanding of the regulation of lipid mobilization, a process being impaired in human islets affected by type 2 diabetes. The completion of the proposal holds potential to identify a new target that will preserve beta cell health under overnutrition and improve a treatment of type 2 diabetes.

PI_NAMEs: IMAI, YUMI  (contact)

PROJECT_TERMS: Acceleration;Affect;Beta Cell;blood glucose regulation;Cell Physiology;Cells;Data;Defect;Development;Emotional;endocrine pancreas development;endoplasmic reticulum stress;Event;Exhibits;Exocytosis;Failure;Fatty Acids;functional decline;Functional disorder;functional loss;Glucose;Goals;Health;High Prevalence;Human;Impairment;improved;Inflammation;insulin granule;insulin secretion;insulin sensitivity;islet;knock-down;Lipase;Lipid Mobilization;Lipids;Lipolysis;Mental Depression;mitochondrial dysfunction;Modeling;Molecular;Nature;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;novel;Overnutrition;Oxidative Stress;palmitoylation;Pathogenesis;Pathway interactions;perilipin;pharmacologic;Phenotype;Physiological;Population;Post-Traumatic Stress Disorders;preservation;Prevalence;prevent;Process;protein complex;Protein S;Regulation;Reporting;response;Role;Shiga-Like Toxin I;Signal Transduction;SNAP receptor;Stress;Structure of beta Cell of islet;syntaxin 1A;Testing;Triglycerides;Type 2 diabetic;Veterans

PROJECT_TITLE: A role and regulation of glucose responsive lipolysis in pancreatic beta cells


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Genetics;Neurosciences;Pediatric

ORG_CITY: BOSTON

ORG_DEPT: BIOLOGY

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: PROJECT NARRATIVE Touch is crucial for detecting pain and pleasure alike, and different neuronal subtypes of the somatosensory dorsal root ganglia relay different qualities of touch into the central nervous system. My research will characterize the gene expression programs that orchestrate the development of these different types of sensory neurons and the role that sensory activity plays in establishing these programs and wiring the corresponding neural circuits. This work will provide insight into the developmental genetic programs that regulate sensory neuron growth, function, and, in many cases, recovery after injury.

PI_NAMEs: SHUSTER, SCOTT ANDREW (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Address;Affect;Afferent Neurons;Anatomy;Auditory;Auditory system;Cell Physiology;Central Nervous System;Chromatin;Data;Development;developmental genetics;developmental neurobiology;diabetic;Enhancers;experience;experimental study;Gene Expression;Gene Expression Profile;Genes;Genetic;Genetic Transcription;in vivo;injury recovery;insight;Ion Channel;Joints;Life;Light;Morphology;mouse genetics;Mus;Nature;neural circuit;neuron development;neuronal growth;Neurons;Pain;Peripheral Nervous System Diseases;Physiological;Physiology;Play;pleasure;postnatal;postnatal development;programs;Property;Proteins;pup;Research;response;RNA;Rodent;Role;Sensory;sensory stimulus;sensory system;Shapes;single nucleus RNA-sequencing;somatosensory;Specific qualifier value;Spinal Ganglia;Stimulus;System;Techniques;Testing;timeline;tool;Touch sensation;Transcriptional Regulation;Vibrissae;Visual;Visual System;Visualization;Work

PROJECT_TITLE: The Role of Mechanosensory Activity in the Transcriptional Maturation of Primary Somatosensory Neurons

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Human Genome;Mental Health;Mental Illness;Neurosciences;Pediatric;Schizophrenia;Serious Mental Illness;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: HADLEY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

PHR: Synaptic dysfunction serves as a key cellular substrate for the pathogenesis of multiple neuropsychiatric disorders, including autism spectrum disorders and schizophrenia. However, the molecular basis of such synaptic malfunctioning is not understood in these disorders. This proposal will use cutting-edge methodologies in stem cell and neuroscience to explore the molecular and cellular mechanisms of synaptic dysfunction in schizophrenia, which are fundamental to our understanding of disease pathogenesis and identification of novel therapeutic treatments.

PI_NAMEs: PAK, CHANGHUI  (contact)

PROGRAM_OFFICER_NAME: PANCHISION, DAVID M

PROJECT_TERMS: 3-Dimensional;Affect;Animals;Astrocytes;autism spectrum disorder;Autopsy;Biochemistry;Biological;Bipolar Disorder;Brain;Brain Diseases;Calcium;Calmodulin;Cell Adhesion Molecules;cell type;Cells;Characteristics;Cognition Disorders;conditional knockout;Congenital cerebellar hypoplasia;Defect;Development;Disease;disease model;Dissection;Dopamine;Electrophysiology (science);Engineering;Event;excitatory neuron;Experimental Designs;Forebrain Development;Functional disorder;Gender;Genetic;genetic analysis;genetic variant;Genome engineering;genome sequencing;genome-wide;Genomics;Glutamates;Goals;Grant;Heterozygote;Human;human embryonic stem cell;Image;immunocytochemistry;Immunoprecipitation;Impairment;In Vitro;Induced Neurons;induced pluripotent stem cell;inhibitory neuron;Intellectual functioning disability;Invertebrates;Knock-out;knockout gene;Link;live cell imaging;loss of function;Maintenance;Mass Spectrum Analysis;Mediating;Mental disorders;Methodology;Methods;Microcephaly;Modeling;Molecular;Molecular Profiling;Mood Disorders;Mus;mutant;Mutation;Nature;nerve stem cell;neurodevelopment;Neuronal Differentiation;Neurons;neuropsychiatric disorder;Neurosciences;neurotransmitter release;novel;novel therapeutics;overexpression;Pathogenesis;Pathology;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Perinatal mortality demographics;Pharmaceutical Preparations;Phenotype;Pontine structure;presynaptic;Probability;Protein Kinase;Protein Kinase Interaction;Protein-Serine-Threonine Kinases;Proteins;Proxy;Reporting;Research;Risk Factors;risk variant;Role;Scaffolding Protein;Schizophrenia;schizophrenia risk;Signal Transduction;single cell genomics;single-cell RNA sequencing;Societies;Specific qualifier value;spheroids;stem;stem cells;Synapses;synaptic function;Synaptic Transmission;synaptogenesis;Techniques;Testing;Tissues;tool;Translating;Up-Regulation;Viral;Work;X-linked intellectual disability

PROJECT_TITLE: Molecular dissection of synaptic dysfunction in mental disorders


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Burden of Illness;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Drug Abuse (NIDA only);Fentanyl Misuse and Addiction;HIV/AIDS;Hepatitis;Hepatitis - C;Infectious Diseases;Liver Disease;Methamphetamine;Opioid Misuse and Addiction;Opioids;Physical Injury - Accidents and Adverse Effects;Prevention;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: LA JOLLA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: This study will characterize trends in incidence of HIV, HCV and OD associated with binational drug markets and drug tourism (DT) between San Diego (SD) and Tijuana (TJ), Mexico. We will incorporate longitudinal data on binational retail drug markets and HIV and HCV sequencing data into dynamic mathematical models to forecast future HIV, HCV and OD incidence trends. This study addresses both the NIDA’s HEAL initiative and the Trans-NIH plan of the OAR, by conducting time-sensitive research to inform implementation of timely interventions to reduce incidence of HIV, HCV and OD.

PI_NAMEs: STRATHDEE, STEFFANIE A. (contact)

PROGRAM_OFFICER_NAME: DUNSTON, SHEBA KING

PROJECT_TERMS: Address;Border Community;Border Crossings;Characteristics;Cities;Cocaine;cohort;Country;Coupled;Data;Data Collection;Disease Outbreaks;Disparity;Drug Formulations;drug market;Drug Prescriptions;epidemiologic data;Epidemiology;Ethnography;Female;Fentanyl;Future;Geography;Half-Life;Health;Heating;Helping to End Addiction Long-term;Hepatitis C Incidence;Hepatitis C virus;Heroin;HIV;HIV/HCV;Incidence;Injecting drug user;Injections;Intervention;Laws;Lead;male;Marketing;mathematical model;Mediating;Methamphetamine;Mexico;Modeling;Molecular Epidemiology;Monitor;National Institute of Drug Abuse;Needle Sharing;non-drug;Outcome;Overdose;Penetration;Persons;Pharmaceutical Preparations;Powder dose form;prescription opioid;prevent;preventive intervention;Price;prospective;Relaxation;Reporting;Research;Risk Behaviors;Route;Sampling;structural determinants;Syringes;Tars;Testing;Time;trafficking;transmission process;trend;United States National Institutes of Health;Virus

PROJECT_TITLE: Ethno-epidemiology of HCV, HIV and Overdose associated with Drug Markets and Drug Tourism

STUDY_SECTION: PPAH

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


FUNDING_MECHANISM: OTHERS

ORG_CITY: LOS ANGELES

ORG_NAME: VA GREATER LOS ANGELES HEALTHCARE SYSTEM

PHR: Women's health and mental health are research priority areas for VA. Posttraumatic stress disorder (PTSD) is prevalent among women Veterans, but many do not engage in evidence-based psychotherapies for PTSD (i.e., PTSD treatment). Insomnia is a risk factor for PTSD development and severity. Healthy sleep is associated with improved mood, daytime functioning, and increased emotion regulation, all of which may increase PTSD treatment engagement and improve treatment outcomes. Cognitive Behavioral Therapy for Insomnia (CBT-I; first-line treatment for insomnia) may reduce treatment barriers and offer a novel, brief, and evidence-based approach to increase PTSD treatment engagement in women Veterans. We will pilot test the effect of trauma-informed CBT-I on PTSD treatment readiness and engagement among women Veterans within insomnia and PTSD and conduct qualitative interviews with pilot trial completers and non-completers to better understand the facilitators of and barriers to PTSD treatment engagement among women Veterans.

PI_NAMEs: CARLSON, GWENDOLYN  (contact)

PROJECT_TERMS: Address;Aftercare;Alternative Therapies;alternative treatment;Appointment;Area;Award;Behavior Therapy;brief intervention;Caring;Clinical Practice Guideline;Cognitive;Cognitive Therapy;Comorbid Insomnia;comorbidity;Data;Development;Diagnosis;diagnostic criteria;Disease remission;Early treatment;Effectiveness;effectiveness trial;eligible participant;emotion dysregulation;emotion regulation;emotional experience;evidence base;experience;Feedback;Feeling suicidal;follow-up;Future;Goals;Health Services Accessibility;improved;improvement on sleep;Individual;innovation;Intervention;Intervention Studies;Interview;Knowledge;Learning;Measures;Mental Health;Methodology;Methods;Modeling;Moods;novel;novel strategies;Participant;Patient Care;patient engagement;Patients;Perception;Phase;pilot test;pilot trial;Post-Traumatic Stress Disorders;preference;Preparation;primary outcome;Process;programs;Protocols documentation;Provider;provider behavior;psychiatric comorbidity;psychiatric symptom;psychoeducation;Psychotherapy;Publishing;Randomized;Readiness;Recommendation;recruit;Reporting;Research;Research Priority;Risk Factors;Role;Sampling;Schedule;self help;Services;Severities;Sleep;Sleep Disorders;Sleeplessness;social stigma;Structure;success;symptomatic improvement;Symptoms;Time;Training;Training Programs;Trauma;treatment as usual;treatment choice;treatment optimization;Treatment outcome;Variant;Veterans;Woman;Women's Health;Women's prevalence;women's treatment;Work

PROJECT_TITLE: Increasing PTSD Treatment Engagement in Women Veterans: Role of CBT for Insomnia

STUDY_SECTION_NAME: Research Career Scientist[MRA0]


NIH_SPENDING_CATS: Cancer

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Project Narrative  Directly targeting unfolded proteins to selectively induce unfolded protein response (UPR) mediated apoptosis in cancer cells is a novel therapeutic modality. The major goal in this application is to evaluate isatin- derived spirocyclic dimers as novel UPR activators in proof-of-concept studies.

PI_NAMEs: NATARAJAN, AMARNATH (AMAR)  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Acidosis;Alkynes;analog;Antineoplastic Agents;Apoptosis;Avidin;Azides;Binding;Biotin;Ca(2+)-Transporting ATPase;Calcium;cancer cell;Cancer cell line;Cancer Model;cancer therapy;Cells;Chemicals;Chemistry;Clinical;crosslink;Cysteine;Cytoplasm;design;Development;dimer;efficacy evaluation;Endoplasmic Reticulum;endoplasmic reticulum stress;Evaluation;experience;Failure;Foundations;Goals;Growth;Hematologic Neoplasms;imaging study;improved;In Situ;in vivo;in vivo Model;Induction of Apoptosis;inhibitor;Isatin;Libraries;live cell imaging;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;misfolded protein;Mitochondria;Modality;Modification;Normal Cell;novel;novel therapeutics;Nuclear;nutrient deprivation;oncogene addiction;Oncogenes;ovarian neoplasm;pancreatic cancer model;Patients;Pharmacodynamics;Process;programs;Proteasome Inhibitor;protein crosslink;Proteins;Proteome;proteostasis;Reporting;response;Sarcoplasm;Signal Transduction;small molecule;Solid Neoplasm;Stress;stressor;Structure-Activity Relationship;success;Surface;synergism;Testing;Thapsigargin;Therapeutic;Toxic effect;trafficking;Translating;tumor growth;Tumor Suppressor Genes;Tumor Suppressor Proteins;Ubiquitinated Protein Degradation;Up-Regulation;Velcade;Xenograft Model

PROJECT_TITLE: UPR Activators for Cancer Therapy

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


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

PI_NAMEs: MAGNUSON, TERRY R (contact)

PROJECT_TERMS: Adoption;Age;anti-cancer research;Automobile Driving;Award;Basic Science;Behavioral;Bioinformatics;Biological Models;Biology;Businesses;cancer care;Cancer Center Support Grant;Cancer Etiology;cancer genetics;cancer genomics;cancer prevention;cancer therapy;Catchment Area;Categories;Cells;Characteristics;Childhood;Chromatin;Clinical;clinical application;clinical care;clinical translation;Communities;community engagement;Community Outreach;Complement;Comprehensive Cancer Center;Computational Biology;Constitution;Coupling;Data;data handling;Development;Developmental Therapeutics Program;diagnostic tool;Direct Costs;Disease Management;DNA;DNA Sequence;drug discovery;Educational Activities;Educational Curriculum;Educational process of instructing;Elements;Environment;Environmental Risk Factor;Epigenetic Process;epigenomics;Ethics;Evaluation;exome;experience;Extramural Activities;Faculty;Faculty Recruitment;fly;Foundations;Funding;Gene Combinations;Gene Expression;Gene Expression Regulation;Generations;Genes;Genetic;Genetic Polymorphism;Genetic Research;Genetic Transcription;genome-wide;genomic data;genomic variation;Genomics;Genotype;Germ Lines;Grant;Growth;Health;Healthcare;high throughput technology;Human;improved;Individual;Informatics;Infrastructure;innovation;insight;Institution;interdisciplinary approach;Investigation;Investments;Laboratories;Laboratory Organism;Large-Scale Sequencing;Leadership;Lesion;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Medical Oncologist;Melanoma;member;model organism;Mus;Mutation;new technology;novel;Outcome;Patient Care;Patients;Pediatric Oncologist;Peer Review;Pharmaceutical Chemistry;Phenotype;Policies;Population;Population Study;post-doctoral training;Precision Health;precision oncology;Precision therapeutics;Predisposition;prevent;Process;Program Reviews;programs;Provider;Publishing;Recommendation;Regulator Genes;Renal Carcinoma;Research;research clinical testing;Research Personnel;Resources;Scientist;Secure;Shapes;Somatic Mutation;Structure;synergism;System;Target Populations;Technology;Therapeutic;Therapeutic Intervention;Toxic effect;Training and Education;transcriptome sequencing;transcriptomics;translational oncology;Translational Research;tumor;tumorigenesis;UNC Lineberger Comprehensive Cancer Center;Variant;Vision;whole genome;Yeasts

PROJECT_TITLE: Cancer Genetics Research Program


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE Class switch recombination and somatic hypermutation is essential for B cell-mediated immunity as its failure leads to immunodeficiency syndromes in humans. On the other hand, aberrant class switch recombination and somatic hypermutation is directly responsible for the ontogeny of mature B cell lymphomas, the most common lymphoma in humans. The goal of this application is to understand the mechanisms that promote genomic alterations in B cells to promote immunity while simultaneously preventing collateral damage. The proposal is therefore directly related to both human immunodeficiencies and B cell oncogenesis.

PI_NAMEs: CHAUDHURI, JAYANTA  (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: activation-induced cytidine deaminase;Affinity;Amino Acids Activation;Antigens;ATP phosphohydrolase;ATPase Domain;B-Cell Lymphomas;B-Lymphocytes;Base Excision Repairs;Binding;cancer type;Cell Death;Cells;Cellular Immunity;CHD4 gene;Chromatin;Chromosomal translocation;Deamination;Deletion Mutation;density;Deoxycytidine;Deoxyuridine;DNA;DNA Damage;DNA Double Strand Break;DNA Repair;DNA Repair Gene;DNA Sequence Alteration;Double Strand Break Repair;Exons;experimental study;Failure;Funding;Generations;Genes;Genetic;Genetic Recombination;genome integrity;Goals;Growth;Heavy-Chain Immunoglobulins;Human;IgE;Immune response;Immunity;immunodeficiency;Immunoglobulin A;Immunoglobulin Class Switching;Immunoglobulin Constant Region;Immunoglobulin G;Immunoglobulin Genes;Immunoglobulin M;Immunoglobulin Somatic Hypermutation;Immunoglobulin Switch Recombination;Immunologic Deficiency Syndromes;Impairment;influenza infection;insight;Knock-in Mouse;Knowledge;Lesion;Lymphoma;Mature B-Lymphocyte;Mediating;Mismatch Repair;Modeling;Molecular;mouse model;Mus;Mutant Strains Mice;Mutate;Mutation;novel;Nucleosomes;Pathologic Mutagenesis;Patients;Phase;Phenocopy;preservation;prevent;Proteins;Reaction;recruit;repaired;response;Role;Testing;tool;tumorigenesis;unpublished works;Work

PROJECT_TITLE: Mechanistic Elucidation of Class Switch Recombination and Somatic Hypermutation

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: PHILADELPHIA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Nanocarriers provide delivery of cargo mRNA to liver, enabling the therapeutic and prophylactic use of this powerful biological agent. However, delivery to other organs remains a major unmet challenge. We propose to achieve this goal by conjugating to RNA nanocarriers molecules with specific affinity to markers typical of distinct types of endothelial cells lining blood vessels. Our preliminary results indicate that using antibodies to such markers enables highly effective and selective delivery and effect of RNA nanoparticles in the lungs, spleen, and brain. We will comprehensively characterize the targeting, its mechanisms and potential medical utility, and translate the best formulation(s) into the clinically useful format.

PI_NAMEs: MUZYKANTOV, VLADIMIR R (contact);WEISSMAN, DREW

PROGRAM_OFFICER_NAME: XIAO, LEI

PROJECT_TERMS: Acute Lung Injury;Affinity;Anti-Inflammatory Agents;Antibodies;Area;Benchmarking;Binding;Biological;Biological Products;Biological Response Modifier Therapy;Blood Vessels;Brain;Cell Adhesion Molecules;Cell Line;Cell membrane;cell type;Cells;Cerebrovascular system;Cerebrum;Clinical;clinical application;Coupled;Development;Disease;Dose;Drug Delivery Systems;Drug Kinetics;Elements;Encephalitis;Endocytosis;Endothelial Cells;Endothelium;Engineering;Epitopes;Extrahepatic;Flow Cytometry;Formulation;Functional disorder;Future;Gene Proteins;gene synthesis;Goals;Human;in vivo;Inflammation;Intercellular adhesion molecule 1;intravenous injection;Isotopes;lead candidate;Ligands;lipid nanoparticle;Liver;Lung;Maps;Medical;Messenger RNA;Methods;Microscopy;Modeling;Modification;mouse model;Mus;nanobodies;nanocarrier;nanomedicine;nanoparticle;Nanotechnology;nanotechnology platform;novel;novel strategies;Organ;Pharmacotherapy;Pilot Projects;prophylactic;protective effect;Proteins;Pulmonary Inflammation;real-time images;Recombinants;Reporter;RNA;RNA delivery;Signal Transduction;Site;spatiotemporal;Specific qualifier value;Spleen;Stroke;Surface;targeted treatment;Testing;Therapeutic;therapeutic gene;Thrombomodulin;Thrombosis;thrombotic;Time;Tissues;transgene expression;Transgenes;Translating;Translations;uptake;Vascular Cell Adhesion Molecule-1

PROJECT_TITLE: Vascular Targeting of Nanocarriers for RNA

STUDY_SECTION: NANO

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

ORG_CITY: BALTIMORE

ORG_DEPT: ORTHOPEDICS

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Osteoarthritis and spinal degeneration are among the most prevalent diseases leading the acceleration of normal aging, mobility decline, and frailty. Aberrant remodeling of subchondral bone in joints and porosity in vertebral endplates may play a central role in decline of mobility and in frailty. In the proposed studies, a team of scientists at Johns Hopkins University School of Medicine from different disciplines and with complementary expertise will work together to address the critical questions in skeletal joint degeneration which leads to accelerated aging and frailty that will provide foundational mechanistic insights for potential therapeutic treatments.

PI_NAMEs: CAO, XU  (contact)

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: Acceleration;Address;Age;age acceleration;Aging;aging process;angiogenesis;Arthralgia;Arthritis;articular cartilage;Axon;Basic Science;Biometry;Bone Marrow;burden of illness;calcification;Cause of Death;Cell Aging;Chronic Disease;Compensation;Consensus;cost;Degenerative polyarthritis;Development;disability;Discipline;Disease;Experimental Models;frailty;functional decline;Functional disorder;Future;Histology;Human;improved;in vivo;in vivo Model;Individual;Injections;insight;Intervertebral disc structure;joint destruction;Joints;Lead;Life Expectancy;Longevity;Low Back Pain;Macrophage;mechanical load;medical attention;medical schools;Mobility decline;Modeling;Morphology;mouse model;Mus;Nerve;nerve supply;normal aging;NTN1 gene;old mice;Osteoclasts;Pain;pain behavior;pain reduction;Pathogenesis;Patients;Persons;Physicians;Physiologic Ossification;Physiological;platelet-derived growth factor BB;Play;Population;Porosity;Positioning Attribute;Process;Program Research Project Grants;PTH gene;Quality of life;Reporting;Research;Research Personnel;Risk;Risk Factors;Role;Scientist;Sclerosis;Secretory Cell;senescence;senescent cell;Sensory;Signal Transduction;skeletal;Skeleton;Spinal;spine bone structure;subchondral bone;Therapeutic;therapeutic target;Training;Transforming Growth Factors;translational applications;Traumatic Arthropathy;United States;Universities;Vertebral column;Work

PROJECT_TITLE: Skeleton and Joint Degeneration with Aging


NIH_SPENDING_CATS: Aging;Chronic Pain;Pain Research

PROJECT_TERMS: Administrator;Advisory Committees;age acceleration;age related;Aging;aging process;Arthralgia;Attenuated;Award;Basic Science;Budgets;Cause of Death;Cell Aging;Cessation of life;chemokine;Chronic Disease;Clinical Research;Clinical Trials;collaborative environment;Communication;Communities;cytokine;data management;data platform;Development;Disease;Education and Outreach;Ensure;Equity;Faculty;frailty;Functional disorder;Funding;Goals;Grant;Histology;improved;improved mobility;in vivo;Individual;Inflammatory;Infrastructure;Institution;Interdisciplinary Study;Internet;joint destruction;Joints;Leadership;Life;Life Expectancy;life span;Longevity;Medical;meetings;Mission;Mobility decline;Monitor;Musculoskeletal;normal aging;operation;osteoarthritis pain;Output;Pain;Peptide Hydrolases;Physical activity;Physical Function;Porosity;premature;Productivity;Program Research Project Grants;programs;Quality of life;Reporting;Research;Research Design;Research Personnel;Resources;Role;Schedule;Sclerosis;Secure;senescence associated secretory phenotype;senescent cell;Services;Skeleton;Spinal;Statistical Data Interpretation;subchondral bone;success;System;Tissues;Translational Research;United States;Universities;Vertebral column;web platform

PROJECT_TITLE: Admin Core


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Immunotherapy;Neuroblastoma;Neurosciences;Orphan Drug;Precision Medicine;Rare Diseases

PI_NAMEs: MILOWSKY, MATTHEW I (contact)

PROJECT_TERMS: Area;Award;Basic Science;bench to bedside;Biological Markers;biomarker development;Biomedical Engineering;Cancer Center;Cancer Center Support Grant;Cancer Patient;cancer therapy;cancer type;career;Catchment Area;Cell Therapy;Cellular immunotherapy;chimeric antigen receptor T cells;Clinic;Clinical;Clinical Research;Clinical Trials;Clinical Trials Cooperative Group;Clinical Trials Design;clinically relevant;Collaborations;community engagement;Community Health Education;Community Outreach;Conduct Clinical Trials;Correlative Study;Coupled;Death Rate;design;Development;Diagnosis;Direct Costs;Disease;Disparity;DNA sequencing;drug development;early phase clinical trial;early phase trial;Endometrial;Enrollment;Ensure;Event;Explosion;Extramural Activities;Faculty;Faculty Recruitment;FDA approved;Fostering;Funding;Future;Genomic approach;Genomics;Glioblastoma;Grant;Image;Immune checkpoint inhibitor;immunoengineering;Immunooncology;immunotherapy trials;improved;innovation;Institution;interdisciplinary approach;Intervention Trial;Investments;K-Series Research Career Programs;leukemia;liquid biopsy;Lymphoma;Malignant neoplasm of ovary;Malignant neoplasm of prostate;Malignant Neoplasms;meetings;member;Mentored Clinical Scientist Development Program;Molecular;molecular marker;Multiple Myeloma;Nature;Neuroblastoma;new technology;next generation;next generation sequencing;North Carolina;novel;novel imaging technology;novel therapeutics;Observational Study;Pancreas;Pathologist;Patient-Focused Outcomes;Patients;Peer Review;Pharmaceutical Preparations;Phase;Physicians;pre-clinical;precision medicine clinical trials;predictive marker;programs;Protocols documentation;Publishing;Radiochemistry;radiologist;Radiology Specialty;Research;Research Personnel;Scientist;Site;skills;Solid Neoplasm;success;Technology;Testing;Therapeutic;Therapeutic Clinical Trial;Tissues;Training;Training and Education;Translating;translational oncology;Translational Research;translational research program;translational scientist;Translational trial;Translations;treatment trial;tumor;tumor microenvironment;Work;Writing

PROJECT_TITLE: Clinical Research Program


NIH_SPENDING_CATS: Aging;Biomedical Imaging;Cardiovascular;Clinical Research;Heart Disease;Heart Disease - Coronary Heart Disease;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: I propose to work on sensing and understanding innate immunity in ischemic heart disease. I will ask the overarching question how cardiovascular disease, and more specifically the risk factor hypertension, affects innate immune cell production in the bone marrow.

PI_NAMEs: NAHRENDORF, MATTHIAS  (contact)

PROGRAM_OFFICER_NAME: DANTHI, NARASIMHAN

PROJECT_TERMS: Affect;Atherosclerosis;Blood Vessels;Body System;Bone Marrow;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;Cells;Circulation;Data;Disease;Exposure to;Goals;Hematopoiesis;Hematopoietic stem cells;Hypertension;Image;image translation;Imaging Device;Immune;in vivo;Inflammatory;intravital microscopy;Knowledge;Leukocytes;Magnetic Resonance Imaging;migration;mortality;Myocardial Ischemia;Natural Immunity;new therapeutic target;Organ;Output;Pathway interactions;Patients;Positron-Emission Tomography;Production;progenitor;Risk Factors;Science;stem cell niche;stem cell proliferation;Time;Work

PROJECT_TITLE: Imaging organ system interfaces in ischemic heart disease


ORG_CITY: NASHVILLE

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: TN

PHR: Project Narrative Chronic infection with the indolent bacterium Helicobacter pylori is the number one risk factor for developing gastric cancer. This project is designed to investigate underappreciated cell-specific, anti-inflammatory role of the IL-17 receptor signaling in control of inflammation and carcinogenesis. It is expected that data garnered will help identify people who are at greater risk of developing gastric cancer; ultimately leading to the development of tools that will be leveraged in either biomarker development or as supplemental immunotherapies in H. pylori infected people.

PI_NAMEs: ALGOOD, HOLLY MARIE SCOTT (contact)

PROJECT_TERMS: Acute;adaptive immune response;Adaptor Signaling Protein;Address;Affect;American Cancer Society;Animal Model;Anti-Inflammatory Agents;Antibodies;antimicrobial;Antimicrobial Resistance;Area;Automobile Driving;B-Lymphocytes;Bacteria;Bacterial Infections;biobank;Biological Assay;Biology;biomarker development;biomarker identification;cancer diagnosis;Cancer Patient;carcinogenesis;CD4 Positive T Lymphocytes;cell type;Cells;Cessation of life;chemokine;Chronic;chronic infection;Complex;cytokine;Data;design;Development;Diet;Disease;Environmental Risk Factor;Epithelial Cells;Equation;Equilibrium;Exhibits;Feedback;Fibroblasts;Future;gastric carcinogenesis;Gastric mucosa;Gastric Tissue;Gastritis;gastrointestinal epithelium;Gene Targeting;Genetic Transcription;Goals;Helicobacter Infections;Helicobacter pylori;Helicobacter Pylori-Related Malignant Neoplasm;Histologic;Human;human tissue;IL17 gene;Immune;Immune response;immunopathology;Immunotherapeutic agent;Immunotherapy;In Vitro;Indolent;Infection;Inflammation;Inflammatory;Inflammatory Response;interleukin-21;Knock-out;Lesion;Location;Lymphocyte;Lymphocyte Activation;Malignant Neoplasms;malignant stomach neoplasm;Mediating;microbial;Modeling;Molecular Biology Techniques;mouse model;Mus;Mutant Strains Mice;neutrophil;Neutrophil Infiltration;Outcome;Oxidative Stress;pathogen;pathogenic bacteria;pathogenic fungus;Pathogenicity;Pathologic;Pathology;Pathway interactions;Peptic Ulcer;Persons;Play;potential biomarker;premalignant;Production;progression marker;Proliferating;receptor;Receptor Signaling;recruit;Regulation;Research;response;Risk;Risk Factors;Risk Reduction;Role;Signal Pathway;Signal Transduction;Smoking;Specimen;Stomach;Stromal Cells;T cell differentiation;T-Lymphocyte;Testing;Tissue Microarray;Tissues;TNF Receptor-Associated Factors;tool;tool development;TRAF4 gene;Transgenic Mice;translational impact;tumor progression;ubiquitin isopeptidase;Vaccines;Virulence Factors;Wild Type Mouse

PROJECT_TITLE: The role of T cell derived cytokines in Helicobacter pylori


NIH_SPENDING_CATS: Aging;Arthritis;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Clinical Research;Neurosciences;Osteoarthritis;Pain Research

PI_NAMEs: ZHEN, GEHUA  (contact)

PROJECT_TERMS: 3-Dimensional;age related;age related changes;Aging;Animal Model;Animals;articular cartilage;Behavior;behavior test;Biomechanics;Blinded;bone;Cartilage;Categories;Charge;Classification;Clinical;Communication;conditioned place preference;Continuing Education;cost;Data;Data Analyses;Degenerative Disorder;Degenerative polyarthritis;design;drug candidate;Ensure;Environment;Equipment;Evaluation;experience;experimental study;Fast Green;Functional disorder;gait examination;Goals;Grouping;Histologic;Histology;Histopathologic Grade;Histopathology;Human Resources;Hyperalgesia;Image Analysis;in vivo;in vivo imaging;in vivo Model;Individual;insight;International;Intervertebral disc structure;Investigation;joint destruction;Joints;Knee joint;Laboratories;Laboratory Personnel;lumbar vertebra bone structure;Measurement;Mechanics;Medial meniscus structure;member;Methods;microCT;Microsurgery;Modeling;Morphology;mouse model;multidisciplinary;operation;Operative Surgical Procedures;Organism;Outcome;Pain;Pathogenicity;Pathologic;Persons;physically handicapped;pre-clinical;pro-aging;Procedures;Program Research Project Grants;programs;Protocols documentation;Reproducibility;Reproducibility of Results;Research;Research Personnel;Resources;Running;Scanning;Services;Severities;skeletal;Skeleton;Societies;Specialist;Spinal;Spinal Ganglia;Stains;Standardization;subchondral bone;Symptoms;System;Testing;Therapeutic;Time;tissue preparation;Tissues;tomography;Training;Translating;Variant;Vascularization;Vertebral column

PROJECT_TITLE: In Vivo Model and Histology Core


ORG_CITY: INDIANAPOLIS

ORG_NAME: RLR VA MEDICAL CENTER

ORG_STATE: IN

PHR: The veteran population develops chronic kidney disease (CKD) at a higher rate than the general population. Patients with CKD are at an increased risk of fracture and if a fracture occurs, patients with CKD have a greater risk of death compared to other populations. Unfortunately, treatments aimed at reducing fracture risk in CKD patients are limited in part due to the lack of extensive studies. The goal of this project is to understand a key component of the CKD-induced bone fragility – cortical porosity. Specifically, we propose experiments that will help determine the mechanisms underlying porosity infilling and how this, combined with maximizing the material properties of bone tissue, can increase bone mechanical properties. The results of these studies will provide a basis for improving the quality of life of veterans suffering from CKD.

PI_NAMEs: ALLEN, MATTHEW R (contact)

PROJECT_TERMS: Address;Adenine;Affect;Age;analog;Animal Diseases;Animal Model;Animals;Area;Biological Assay;bisphosphonate;bone;Bone Diseases;bone fragility;bone mass;Bone Matrix;Bone Resorption;Bone Tissue;Cells;Cessation of life;Chronic Kidney Failure;cinacalcet;Clinic;Clinical;clinically relevant;Collagen;Combined Modality Therapy;cortical bone;Data;Death Rate;Deterioration;Development;Disease Progression;Dose;Effectiveness;effectiveness evaluation;experimental study;FDA approved;Female;Fracture;fracture risk;General Population;Goals;Health;Homeostasis;Hospitalization;human disease;improved;in vivo;Individual;Intervention;Kidney Diseases;Laboratories;male;Measures;mechanical properties;Mechanics;Mediating;Methods;microCT;military veteran;Minerals;Modeling;Modification;mortality;mortality risk;nanoindentation;novel;novel strategies;Osteogenesis;Osteoporosis;Outcome;Patients;Persons;pharmacologic;Population;Porosity;pre-clinical;Prevalence;prevent;Prevention;Property;PTH gene;Quality of life;Raloxifene;Raman Spectrum Analysis;Rattus;Regimen;Resistance;Risk;Sex Differences;skeletal;substantia spongiosa;Testing;Time;Tissues;Treatment Efficacy;Veterans;Water;Work;X-Ray Computed Tomography

PROJECT_TITLE: Treating bone deterioration associated with chronic kidney disease


NIH_SPENDING_CATS: Aging;Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Immunotherapy;Women's Health Research

PI_NAMEs: CAREY, LISA A (contact)

PROJECT_TERMS: Address;Adherence;African American population;Animal Model;anti-cancer research;Autopsy;Award;Basic Science;Behavior;bench to bedside;Bioinformatics;Biological;Biological Markers;Biology;Breast;Cancer Center Support Grant;cancer health disparity;Cancer Research Project;cancer subtypes;cancer therapy;care outcomes;Catchment Area;Cells;Cellular Structures;Center for Translational Science Activities;Classification;Clinical;clinical care;clinical database;Clinical Research;Clinical Trials;cohort;Collaborations;Communities;community engagement;Community Outreach;Country;County;Data;design;Direct Costs;Discipline;Disease;Disparity;DNA analysis;DNA Integration;DNA sequencing;Elderly;Epidemiologist;epidemiology study;ERBB2 gene;Etiology;experience;Exposure to;Extramural Activities;Faculty;Fostering;Funding;Gene Expression;Genetic;genetic analysis;genetic manipulation;Genome Stability;Genomics;Goals;graduate student;Grant;Growth;Health Sciences;Health Services;Health Services Accessibility;Health Services Research;hormone receptor-positive;human tissue;Immune;Immunocompetent;Immunotherapeutic agent;Immunotherapy;improved outcome;Incidence;Infrastructure;innovation;Institution;Interdisciplinary Study;interest;International;intervention program;Intervention Trial;Investments;large datasets;Leadership;Malignant Breast Neoplasm;Malignant Neoplasms;meetings;member;Metastatic breast cancer;minority disparity;Minority-Serving Institution;Molecular Analysis;mouse model;Multicenter Trials;Mus;Neoplasm Metastasis;Neoplasm Transplantation;new technology;North Carolina;novel;Oncogene Activation;Oncology;Organ;Outcome;outreach;Patients;Peer Review;population based;Population Research;Population Study;Positioning Attribute;predicting response;Primary Neoplasm;programs;prospective;Proteomics;Public Health;Public Hospitals;Publishing;racial disparity;recruit;Regimen;Research;Research Design;Research Personnel;Research Support;Resources;response;RNA;Role;Science;Scientist;Seminal;senior faculty;single cell analysis;Source;State Hospitals;success;Technology;Therapeutic;therapy adherence;Tissues;tool;Training;transcriptome sequencing;transcriptomics;translational oncology;Translational Research;transplant model;treatment optimization;treatment response;treatment trial;triple-negative invasive breast carcinoma;tumor;tumor microenvironment;Tumor Subtype;tumor-immune system interactions;undergraduate student;Woman;Work

PROJECT_TITLE: Breast Cancer Research Program


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Hematology;Infectious Diseases;Lung;Rare Diseases;Sepsis

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative The acute respiratory distress syndrome (ARDS) is a deadly condition that leads to difficulty breathing and low oxygen levels in the blood. Patients with ARDS are treated with mechanical ventilation in the intensive care unit, but this treatment can cause further lung injury. The purpose of this research is to understand the molecular mechanisms that cause lung injury during mechanical ventilation in order to develop new treatments for patients with ARDS.

PI_NAMEs: ENGLERT, JOSHUA A (contact)

PROGRAM_OFFICER_NAME: ESPINOZA GRANDON, INGRID CECILIA

PROJECT_TERMS: Acute Respiratory Distress Syndrome;Alveolar;alveolar epithelium;Annexins;atelectrauma;Attenuated;Binding;Binding Proteins;Blood;Blood capillaries;Breathing;cecal ligation puncture;Cell Death;cell growth;Cell membrane;Cell Physiology;Cells;clinically relevant;Complex;Data;Dysbarism;efficacy testing;Epithelial Cells;Epithelium;Fluorescent Dyes;FRAP1 gene;Functional disorder;Genetic;Growth;Human;Hypoxemia;Impairment;in vitro Model;in vivo;Inflammation;influenza pneumonia;inhibitor;Injury;Intensive Care Units;Knockout Mice;Life;lipid metabolism;live cell microscopy;Lung;Lung Compliance;lung injury;Measures;mechanical force;Mechanical ventilation;Mediating;Membrane;Modeling;Molecular;Monitor;Multiprotein Complexes;Mus;new therapeutic target;novel;novel strategies;Oxygen;Patients;Permeability;pharmacologic;Phospholipids;Phosphorylation;Physiology;Play;pre-clinical;Pre-Clinical Model;pressure;prevent;Protein-Serine-Threonine Kinases;repaired;Research;Respiratory Failure;Role;seal;Sepsis;Serine;Stretching;Supportive care;surfactant;surfactant function;System;Tidal Volume;trafficking;Ventilator;Ventilator-induced lung injury;Volutrauma

PROJECT_TITLE: Dissecting the molecular mechanisms of lung injury during mechanical ventilation

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: Although underrepresented minorities continue to join STEM disciplines, examination of professorial ranks indicates there is a significant leak retaining underrepresented minorities in the biomedical science workforce. Many explanations have been proposed for this leaky pipeline such as poor mentoring, lack of community and a deficiency in research-related skills. We propose a novel summer undergraduate training program to help bridge these gaps, thereby significantly increasing the retention of these talented students in the biomedical sciences.

PI_NAMEs: CAROMILE, LESLIE ANN (contact);DODGE-KAFKA, KIMBERLY L

PROGRAM_OFFICER_NAME: ESPINOZA-PINTUCCI, MARISOL

PROJECT_TERMS: Academic advising;Accreditation;Admission activity;Advertisements;Affect;African American population;Area;Basic Science;Biological;Biological Sciences;Biology;Biomedical Research;Blood Vessels;Cardiology;career;Career Choice;Cognitive;Communities;Competence;Dedications;Dental Schools;Directories;disabled students;disadvantaged student;Doctor of Philosophy;Educational process of instructing;Educational workshop;Electronic Mail;Enrollment;Environment;evidence base;experience;Faculty;faculty research;follow-up;Funding;Future;Goals;Graduate Enrollment;graduate school;Health;Hispanic Populations;holistic approach;implicit bias;improved;Institution;interest;Laboratories;matriculation;medical schools;Mentors;Minority;Names;National Heart, Lung, and Blood Institute;Native Americans;Newsletter;novel;Pacific Islander;Population;Process;programs;Records;recruit;Research;Research Project Grants;Science;science education;skills;STEM field;STEM program;Students;summer program;summer research;symposium;System;Talents;teacher;Teacher Professional Development;Techniques;Telephone;tool;Training;Training Programs;undergraduate student;Underrepresented Minority;underrepresented minority student;Underrepresented Populations;Underrepresented Students;Universities;Update;Visit;Vocational Guidance;web site

PROJECT_TITLE: Increasing Research Experiences for Multicultural Students


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_CITY: BIRMINGHAM

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative It is critical to better understand genetic causes of human neurodevelopmental disorders such as autism, intellectual disability, and schizophrenia and to use animal models of such causes to identify potential treatments. This 5-year R01 proposal capitalizes on significant progress in creating and characterizing two novel animal models of neurodevelopmental disorders that will allow us to rapidly advance this field. Extensive characterization of these new models will allow for a complete understanding of how genetic mutations in these genes alter brain function and behavior, allowing for future studies aimed at correcting altered brain function in the hope of treating behavioral symptoms in both the models and in patients.

PI_NAMEs: POWELL, CRAIG M (contact)

PROGRAM_OFFICER_NAME: HUPALO, SOFIYA

PROJECT_TERMS: 16p11.2;Actins;Adaptor Signaling Protein;Address;Affect;Animal Genetics;Animal Model;Area;autism spectrum disorder;Behavior;Behavioral;Behavioral Symptoms;Binding Proteins;Biochemistry;Brain;brain control;brain morphology;brain size;Cell Culture Techniques;cell motility;Code;communication behavior;Complex;conditional mutant;Copy Number Polymorphism;CUL3 gene;Data;Databases;Dendrites;Development;Disease;DNA Sequence Alteration;Drosophila genus;Exhibits;exome sequencing;experience;Face;FDA approved;Functional disorder;Future;Gene Expression;gene function;gene product;Gene Proteins;Genes;Genetic;Genetic Models;Head;Hela Cells;Heterozygote;Hippocampus;Human;In Vitro;innovation;Intellectual functioning disability;interest;Link;loss of function mutation;Macrocephaly;Microcephaly;model of autism spectrum disorder;Modeling;Molecular;Monomeric GTP-Binding Proteins;Morphology;mouse model;Mus;mutant;mutant mouse model;Mutation;Nature;neurodevelopment;Neurodevelopmental Disorder;neurogenesis;neuron development;Neuronal Dysfunction;Neurons;novel;Pathway interactions;Patients;Pharmacotherapy;Phenotype;Proteins;Proteomics;PTEN gene;Publishing;Recurrence;Regulation;repetitive behavior;Role;Schizophrenia;Signal Pathway;Social Interaction;Structure;Synapses;synaptic function;Synaptic Transmission;Therapeutic;therapeutic target;transcriptomics;Translating;treatment strategy;ubiquitin ligase;ubiquitin-protein ligase;Ubiquitination;Vertebral column;Work;Xenopus;Zebrafish

PROJECT_TITLE: Molecular and Cellular Basis of Neurodevelopmental Disorders


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences

ORG_NAME: LIEBER INSTITUTE, INC.

PHR: Project Narrative This hippocampal-prefrontal circuit is critically involved in multiple aspects of cognition related to executive function and emotional regulation, and implicated in a diverse array of brain disorders and neuropsychiatric illnesses. In this proposal we investigate the cellular and molecular signaling pathways that govern connectivity in this circuit. This proposal is relevant to the part of the NIH mission that pertains to the translation of basic mechanisms causing neurodevelopmental disorders and mental illnesses into innovative treatments.

PI_NAMEs: MARTINOWICH, KERI  (contact)

PROGRAM_OFFICER_NAME: VICENTIC, ALEKSANDRA

PROJECT_TERMS: Affect;Animal Model;Attenuated;Behavior;Behavior Control;Brain Diseases;Brain-Derived Neurotrophic Factor;Cells;Chromosome Mapping;Chronic stress;Cognition;Cognitive;Communication;Coupling;Data;Development;Disease;Electrophysiology (science);emotion regulation;Emotional;Endoscopy;enhancing factor;Event;executive function;experimental study;Exposure to;fear memory;Fright;Functional disorder;Future;Gene Expression;Genes;Goals;Hippocampus;Impairment;in vivo;in vivo imaging;inducible Cre;innovation;Knowledge;Label;Link;Mediating;Mental Depression;Mental disorders;Mission;Molecular;Molecular Profiling;Morphology;neural;neural patterning;Neurodevelopmental Disorder;Neurons;neuropsychiatric disorder;neuropsychiatry;novel;overexpression;Pathway interactions;Patients;Pattern;Phase;Physiological;Play;Population;Post-Traumatic Stress Disorders;Precipitating Factors;Prefrontal Cortex;Process;programs;Regulation;Research;Research Design;response;Retrieval;Risk Factors;Role;Schizophrenia;Signal Pathway;Signal Transduction;Slice;Stress;Structure;Synapses;Techniques;Translations;United States National Institutes of Health;Viral

PROJECT_TITLE: Molecular and Cellular Correlates of Plasticity in Hippocampal-Prefrontal Circuitry

STUDY_SECTION: PMDA

STUDY_SECTION_NAME: Pathophysiological Basis of Mental Disorders and Addictions Study Section[PMDA]


NIH_SPENDING_CATS: Aging;Back Pain;Chronic Pain;Clinical Research;Neurosciences;Pain Research;Prevention

PROJECT_TERMS: Affect;afferent nerve;Afferent Neurons;age acceleration;age related;Aging;Analgesics;Animal Model;Animals;Arachidonic Acids;Attenuated;Avil;Axon;axon growth;axon guidance;behavior test;bisphosphonate;Blood Vessels;Bone remodeling;Cell Aging;Characteristics;Chronic;Chronic Disease;Clinical;Clinical Research;Consensus;cost;cyclooxygenase 2;Data;Degenerative polyarthritis;density;Deterioration;Development;Dinoprostone;Disease;driving force;Elderly;Etiology;Evaluation;Exhibits;experimental study;Frail Elderly;frailty;functional decline;Functional disorder;Future;Health;Histologic;Hypersensitivity;improved;Intervertebral disc structure;joint destruction;Joints;Life;Life Cycle Stages;Longevity;Low Back Pain;Magnetic Resonance Imaging;mechanical force;mechanical load;Mechanics;Mediating;medical attention;mesenchymal stromal cell;Mobility decline;Modeling;mouse model;Mus;Nature;Nerve;nerve supply;Nociceptors;NTN1 gene;old mice;osteoblast differentiation;Osteoclasts;Pain;pain patient;Pathway interactions;Patients;Persistent pain;Persons;Physical activity;Physiologic Ossification;PIK3CG gene;Population;Porosity;Positioning Attribute;PTK2 gene;Quality of life;receptor;Reporting;response;Rest;Risk;Risk Factors;Rodent;Role;senescence;senescent cell;Sensory;sensory mechanism;Signal Transduction;skeletal;Skeleton;Source;Spinal;spine bone structure;subchondral bone;Symptoms;systematic review;Tissues;tomography;Vertebral column;Work;Zoledronic Acid

PROJECT_TITLE: Endplate Sensory Innervations for LBP


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Complementary and Integrative Health;Digestive Diseases;Liver Disease;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine

ORG_CITY: KANSAS CITY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE Acetaminophen overdose is the most common cause of acute liver failure in the United States and the narrow therapeutic window of the current antidote, N-acetylcysteine, and late presentation of most patients, necessitates development of late acting therapies. Based on preliminary data, we propose to study the role of the adenosine A2B receptor in modulating the immune response and influencing liver recovery after APAP overdose in mice. These studies will have an impact on existing treatments and ultimately help develop better therapeutic strategies.

PI_NAMEs: RAMACHANDRAN, ANUP  (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Acetaminophen;acetaminophen overdose;acetaminophen-induced liver injury;Acetylcysteine;Acute Liver Failure;Adenosine A2B Receptor;Agonist;Alternative Therapies;Animal Experiments;Anti-Inflammatory Agents;Antidotes;Area;Biochemistry;Blood specimen;Cell Death;cell injury;Cell Survival;Cells;Cellular biology;Central Vein;Clinic;Clinical;Clinical Trials;clinically relevant;Complement;Complement component C4;Cues;cytokine;Data;Development;drug induced liver injury;drug repurposing;Equilibrium;Event;Excision;fomepizole;Functional disorder;Gene Expression;Genetic;Goals;hepatic necrosis;Hepatocyte;Hepatotoxicity;Hospitals;Hour;Human;Immune;immune cell infiltrate;Immune response;immunoreaction;immunoregulation;improved outcome;in vivo;Infiltration;Inflammatory;Injury;Innate Immune Response;Innate Immune System;insight;Intervention;Laboratories;Literature;Liver;liver ischemia;Liver Regeneration;Macrophage;Mediating;Molecular;monocyte;Mus;Natural regeneration;Necrosis;neutrophil;Neutrophil Infiltration;novel;novel strategies;NTN1 gene;Overdose;patient prognosis;Patients;Pharmaceutical Preparations;pharmacologic;Phenotype;pre-clinical;prevent;Process;Property;Proteins;Publishing;receptor;Recovery;recruit;Regenerative capacity;repaired;Reperfusion Injury;Resolution;response;Role;safety study;single-cell RNA sequencing;spatiotemporal;standard of care;Techniques;Testing;Therapeutic;Therapeutic Intervention;Time;Translating;Translations;United States;Up-Regulation;volunteer;Western World;Work

PROJECT_TITLE: The Immune Response After Drug Induced Hepatotoxicity

STUDY_SECTION: XNDA

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


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Electronic Nicotine Delivery Systems;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Lung Cancer;Prevention;Social Determinants of Health;Tobacco

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PI_NAMEs: BASCH, ETHAN M. (contact)

PROJECT_TERMS: access disparities;Address;Adolescent;Area;Arts;behavior change;Behavior Therapy;Behavioral;Behavioral Sciences;Biometry;Breast;Cancer Burden;cancer care;Cancer Center Support Grant;Cancer Control;Cancer Control Research Program;cancer epidemiology;Cancer Etiology;cancer health disparity;cancer prevention;cancer risk;Cancer Survivor;career;career development;Caregivers;Catchment Area;Cervical;cigarette warning label;Collaborations;college;Colon;Communication;community engagement;Community Outreach;Comparative Effectiveness Research;Complex;cost effective;Databases;Department chair;design;Development;Dietary Intervention;digital;Direct Costs;Discipline;Discipline of Nursing;disparities in morbidity;Disparity;disparity elimination;Disparity population;distinguished professor;Doctor of Philosophy;Education;Electronic cigarette;electronic cigarette use;Evaluation;Evidence based intervention;Extramural Activities;Faculty;Faculty Recruitment;Fellowship;Fostering;Funding;Future;Grant;health application;Health behavior;health communication;health disparity;Health Promotion;Health Services;Health system;Healthcare Systems;Home;Human Papilloma Virus Vaccination;Human Papilloma Virus-Related Malignant Neoplasm;improved;Influentials;Infrastructure;Interactive Communication;Intervention;Intervention Studies;Investments;Journalism;Lead;Leadership;Link;Lung;Malignant neoplasm of ovary;Malignant Neoplasms;Marketing;Medical Oncologist;Medical Oncology;medical schools;member;Mentors;Methodology;mortality disparity;multidisciplinary;North Carolina;novel;Obesity;Outcome;Outcome Study;Outcomes Research;patient oriented;Patient Outcomes Assessments;Patient-Focused Outcomes;Patients;Pattern;Peer Review;Personal Satisfaction;Pharmacy facility;Physical activity;Policies;Policy Making;Policy Research;Population;Population Heterogeneity;Population Sciences;Positioning Attribute;post-doctoral training;Postdoctoral Fellow;pre-doctoral;prevent;Prevention;Prevention strategy;Productivity;programs;Prostate;Provider;Public Health;Public Health Schools;public policy on tobacco;Publications;Publishing;quality of life for cancer survivors;Recording of previous events;recruit;Research;Research Infrastructure;Research Personnel;Resource Sharing;Risk Factors;Sales;Schools;Science;Scientist;screening;Screening for cancer;support network;Survivors;survivorship;symptom management;Technology;Testing;Tobacco use;Training

PROJECT_TITLE: Cancer Prevention and Control Research Program


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Clinical Research;Machine Learning and Artificial Intelligence;Microbiome;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn

ORG_CITY: CHICAGO

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The intestinal microbiome has impact beyond the gut and the existence of a gut-brain axis has been proposed. Preterm infants are at risk for poor neurodevelopmental outcomes. This proposal will study how the changes in bacterial colonization patterns of preterm infants over time from birth until school age impact brain development, and thus school readiness and learning for these vulnerable infants.

PI_NAMEs: CLAUD, ERIKA C (contact)

PROGRAM_OFFICER_NAME: WINER, KAREN

PROJECT_TERMS: 16S ribosomal RNA sequencing;5 year old;Affect;Age;age effect;autism spectrum disorder;Behavior;behavior test;Biological Markers;Birth;Blood specimen;Brain;Child;Clinical;clinical care;clinically relevant;cohort;cytokine;Data;Development;Disease;Elements;Enrollment;experience;Experimental Models;fecal microbiota;Foundations;functional outcomes;Genes;Germ-Free;Gnotobiotic;Goals;Growth;gut microbiome;gut-brain axis;Head circumference;high risk infant;Human;improved;improved outcome;in vivo;Individual;infancy;Infant;Infant Development;infant gut microbiome;infant outcome;innovation;insight;Intelligence;International;intestinal barrier;Investigation;Knowledge;Learning;learning strategy;Link;Machine Learning;machine learning model;Measures;Mental Depression;metabolome;metabolomics;metagenomic sequencing;Metagenomics;Microbe;microbial;microbial based therapy;microbial community;microbiome;microbiota;Modeling;Modification;Monitor;mouse model;multidisciplinary;Mus;myelination;Neonatal;neonatal health;neurodevelopment;Neurodevelopmental Disorder;neuroinflammation;Neurological outcome;Neurons;novel;Nursery Schools;Outcome;Outcome Measure;Participant;Pathway interactions;patient population;Pattern;Population;Populations at Risk;Premature Infant;prospective;Publishing;Readiness;Ribosomal RNA;Risk;Role;Sampling;Schizophrenia;School-Age Population;Schools;Serum;Shotguns;Standardization;stool sample;success;systemic inflammatory response;Techniques;Testing;Therapeutic;therapy design;Time;Vulnerable Populations;Work

PROJECT_TITLE: The Gut Microbiome Brain Axis and Preterm Infants

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-P(02)]


NIH_SPENDING_CATS: Infectious Diseases;Lung

ORG_CITY: PROVIDENCE

ORG_NAME: RHODE ISLAND HOSPITAL

ORG_STATE: RI

PHR: Project Narrative The body's systemic response to trauma (severe injury, hemorrhagic shock, etc.) results in compromised immune function. This ultimately results in high susceptibility to hospital-acquired secondary infections and inflammation that damages organs such as the lungs. Neutrophils are the immune system's first line of defense against bacterial infection, but their response can also cause collateral damage to our tissues. Our research uses multiple approaches to understand how hemorrhagic shock alters neutrophil function, with a goal of developing strategies to modulate neutrophils such that they are better able to eliminate infection without causing damage to host tissue.

PI_NAMEs: LEFORT, CRAIG THOMAS (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Acute;Acute Lung Injury;Animals;Antibiotics;antimicrobial;Bacteria;Bacterial Infections;Blood capillaries;Cell Line;Chimerism;clinically relevant;Coupled;Critical Care;Critical Illness;cytotoxic;Development;Disease;fighting;Functional disorder;fungus;Generations;Genes;Goals;Healthcare;Hemorrhagic Shock;Hospital Mortality;Hospitals;Host Defense;immune function;Immune system;Immune System Diseases;in vivo;Infection;Inflammation;Injury;innovation;irradiation;Knowledge;Lung;Mediating;Mediator;methicillin resistant Staphylococcus aureus;Microfluidics;Modeling;Molecular;Morbidity - disease rate;mouse model;Mus;neutrophil;novel;novel therapeutic intervention;Organ;Organism;Oxidants;Peptide Hydrolases;Predisposition;premature;programs;Research;Respiratory Tract Infections;response;Role;secondary infection;severe injury;stem cells;Supportive care;System;Techniques;Therapeutic Intervention;therapeutically effective;Tissues;trafficking;Transplantation;Trauma

PROJECT_TITLE: Selective Modulation of Neutrophils in Critical Illness

STUDY_SECTION: MRAC

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


NIH_SPENDING_CATS: Clinical Research;Infectious Diseases

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Viral infections represent a significant disease burden in the United States, emphasizing an urgent need to design novel strategies for vaccination and treatment. A promising target for these strategies is an immune cell type known as dendritic cells, which play a central role in orchestrating antiviral responses. The proposed research aims to investigate how a newly discovered dendritic cell subpopulation contributes to the resolution of viral infections, potentially revealing new biological mechanisms that could be harnessed therapeutically.

PI_NAMEs: IDOYAGA, JULIANA  (contact)

PROGRAM_OFFICER_NAME: VAZQUEZ-MALDONADO, NANCY

PROJECT_TERMS: adaptive immune response;Anti-viral Response;Antigen Presentation;Antigen-Presenting Cells;Biological;Biological Assay;burden of illness;Cell Differentiation process;Cell Maintenance;Cell Physiology;cell type;Cells;Characteristics;Data;Dendritic Cells;Dependence;design;Development;Dimensions;experimental study;Future;Genetic;Genetic Transcription;Goals;high dimensionality;Homologous Gene;Human;Immune;immune function;Immune response;immunoregulation;In Vitro;in vivo;Infection;innate immune function;Innate Immune Response;Interferon Type I;Lymphoid;Mediating;Modeling;mouse model;Mus;Myeloid Progenitor Cells;Names;novel;novel strategies;Outcome;Pathway interactions;Phenotype;Play;Population;Process;Production;progenitor;Proteomics;rational design;Research;Resolution;response;Role;sensor;Site;System;T cell response;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;TCF7L2 gene;Testing;Therapeutic;therapeutic development;transcription factor;transcriptomics;United States;vaccination strategy;Viral;Virus;Virus Diseases

PROJECT_TITLE: Transitional dendritic cells: identifying the origin and role of a novel innate immune population during viral infection

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


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

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Breast cancer is the most commonly diagnosed cancer among women in the United States, meaning that identifying effective therapies and improving upon current standard-of-care treatment options is critically important. The research conducted during the F99 phase will explore how the function of dendritic cells is altered during TIM-3 blockade, while the K00 phase will focus on understanding how the location of immune cells within the tumor affects the induction of anti-tumor immunity. Both of these studies will increase our understanding of the mechanisms behind the anti-tumor immune response, and have the potential to inform the design of future immunotherapeutic interventions.

PI_NAMEs: GARDNER, ALYCIA  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: adaptive immune response;Address;Affect;anti-PD-L1;anti-tumor immune response;Antibodies;Antigen Presentation;Antitumor Response;Bone Marrow;Breast Cancer Patient;cancer diagnosis;CD8-Positive T-Lymphocytes;Cell Communication;Cells;chemokine;Chemotactic Factors;chemotherapy;combinatorial;Combined Modality Therapy;Cross Presentation;CTLA4 gene;cytokine;Cytotoxic T-Lymphocytes;Data;Dendritic Cells;design;Disease;draining lymph node;effective therapy;epigenome;experimental study;Future;Gene Expression Profiling;Human;Immune;immune checkpoint blockade;Immune response;Immunity;Immunoglobulins;Immunotherapeutic agent;Immunotherapy;improved;in vivo imaging;Infection;Intervention;Location;lymph nodes;Malignant Breast Neoplasm;Mammary Neoplasms;Masks;Measures;Mediating;migration;Modality;Modeling;molecular subtypes;mouse model;Mucins;Mus;Mutation;Paclitaxel;Pathway interactions;Patients;Phase;phase 3 study;Population;Production;programmed cell death ligand 1;programmed cell death protein 1;Publishing;Regulation;Research;response;Role;Scanning;secondary lymphoid organ;Site;standard of care;Survival Rate;T cell differentiation;T cell infiltration;T cell response;T-Lymphocyte;Techniques;Therapeutic;Treatment Efficacy;treatment response;tumor;Tumor Antigens;Tumor Immunity;tumor microenvironment;United States;Up-Regulation;Woman;women's diagnosis

PROJECT_TITLE: Targeting the Epigenome to Improve Responses to Immunotherapy


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Immunization;Infectious Diseases;Lung;Orphan Drug;Prevention;Rare Diseases;Vaccine Related

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: NARRATIVE The COVID-19 pandemic has resulted in a tragically high number of deaths in the United States due to severe injury of the lungs by the virus. A major complication of the virus is that leads to the build-up of fluid in the lungs because the lung blood vessels are unable to continue their normal function. The research in this proposal will identify new ways to prevent fluid build-up in the lung and test new treatments using virus variants of concern that are highly contagious and escape the immune response activated by currently available vaccines.

PI_NAMEs: REHMAN, JALEES  (contact);RICHNER, JUSTIN

PROGRAM_OFFICER_NAME: ZHOU, GUOFEI

PROJECT_TERMS: 2019-nCoV;ACE2;Acute;Acute Lung Injury;Acute Respiratory Distress Syndrome;Adherens Junction;Affinity;anakinra;antagonist;Binding;Binding Proteins;Biological Response Modifiers;Blood Vessels;cadherin 5;Categories;cell injury;Cell Reprogramming;cell type;Cells;cellular engineering;Cessation of life;Complement;Complication;COVID-19;COVID-19 pandemic;COVID-19 severity;COVID-19 treatment;cytokine;cytokine release syndrome;Data;Death Rate;Development;Disease;Down-Regulation;Edema;Elements;Endothelial Cells;endothelial regeneration;Endothelium;Engineering;Epithelial Cells;Epithelium;Functional disorder;Genetic;Host Defense;Human;humanized mouse;Immune;Immune response;Immune system;Inflammasome;Inflammatory;Inflammatory Response;Injury;Interferon Type I;Interleukin-1 beta;Interleukin-6;Intravenous;K-18 conjugate;Knowledge;Liquid substance;Lung;lung injury;lung vascular injury;Mediating;mortality;mouse model;Mus;Nature;novel therapeutics;Pathogenicity;Patients;Peptide Hydrolases;Peptides;Permeability;pharmacologic;Phase;Predisposition;prevent;Proteins;receptor;Research;response;Role;Route;SARS coronavirus;SARS-CoV-2 spike protein;SARS-CoV-2 variant;severe COVID-19;severe injury;Signal Transduction;single-cell RNA sequencing;Syndrome;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;tissue injury;Tissues;TMPRSS2 gene;Treatment Efficacy;United States;uptake;Vaccination;vaccine access;vaccine response;Vaccines;Variant;variants of concern;Vascular Permeabilities;Viral;Viral Antigens;Virus

PROJECT_TITLE: Mechanisms and Treatment of SARS-CoV-2 induced Lung Endothelial Injury

STUDY_SECTION: RIBT

STUDY_SECTION_NAME: Respiratory Integrative Biology and Translational Research Study Section[RIBT]


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

ORG_CITY: CHAPEL HILL

PI_NAMEs: HENDERSON, LOUISE  (contact)

PROJECT_TERMS: Address;analytical method;Area;Arts;Big Data;Biological Markers;Bladder;Breast;Cancer Burden;cancer care;Cancer Center Support Grant;Cancer Control;cancer epidemiology;Cancer Etiology;cancer health disparity;cancer prevention;cancer risk;cancer site;cancer therapy;Caring;Catchment Area;Clinical;Clinical Research;cohort;Collaborations;college;Colon;Colon Carcinoma;community engagement;Community Outreach;Comprehensive Cancer Center;computer science;computer scientist;Continuity of Patient Care;Data;Data Collection;Data Linkages;data management;Data Science;data sharing networks;deep learning;design;Development;Dimensions;Direct Costs;Early Diagnosis;Endometrium;Epidemiologic Methods;Epidemiologist;Epidemiology;epidemiology study;Etiology;Evidence based intervention;Extramural Activities;Faculty;Faculty Recruitment;Funding;Genetic;Genetic Research;genomic data;Genomics;Grant;Head and Neck Cancer;health disparity;health equity;Health Services;Heterogeneity;Human;improved;Infrastructure;Institution;interdisciplinary collaboration;International;Intervention;Investments;Leadership;Lesion;Link;Lung;Malignant Breast Neoplasm;Malignant Neoplasms;medical schools;Melanoma;member;Mentors;method development;Methods;Molecular;Molecular Epidemiology;Monitor;neoplasm registry;North Carolina;novel;Outcome;Pathology;Pattern;Peer Review;Pharmaceutical Preparations;Pharmacoepidemiology;Pilot Projects;Population;population based;Population Sciences;Population Study;pre-clinical research;Prevention;Prevention approach;Prevention strategy;Productivity;programs;Prostate;public health priorities;Public Health Schools;Publishing;racial diversity;recruit;Registries;Research;Research Personnel;Research Priority;Resource Sharing;Resources;Risk;Science;screening;Screening for cancer;social;sociologist;Sociology;Specimen;Statistical Methods;Strategic Planning;surveillance data;Surveys;survivorship;Training and Education;tumor;Wages

PROJECT_TITLE: Cancer Epidemiology Research Program


NIH_SPENDING_CATS: Aging;Back Pain;Chronic Pain;Clinical Research;Neurosciences;Pain Research

PI_NAMEs: CRANE, JANET  (contact)

PROJECT_TERMS: Acceleration;Address;Affect;age acceleration;aged;Aging;Analgesics;Attenuated;attenuation;Axon;Biology;Body Weight;bone;Bone Marrow;Bone remodeling;Calcium;Cartilage;cartilaginous;Cell Size;Cells;cellular targeting;Chondrocytes;Cilia;Clinical;Clinical Trials Design;Complex;Data;Deceleration;Development;Diffusion;disability;Disease;drug development;Elderly;Etiology;frailty;Functional disorder;Genetic;Histopathologic Grade;Homeostasis;hormonal signals;Hormones;Human;human disease;human model;Hypersensitivity;Hypertrophy;Impairment;improved;In Vitro;Inflammatory;Injections;Intervertebral disc structure;intervertebral disk degeneration;joint destruction;Joints;Knock-out;Knockout Mice;Low Back Pain;Magnetic Resonance Imaging;mechanical allodynia;mechanical load;mechanical properties;Mechanical Stress;Mechanics;mechanotransduction;Mediating;Microfluidics;mineralization;Modeling;mouse model;Mus;Muscle;nerve supply;Neurons;Neurosciences;Nociception;Nociceptors;nucleus pulposus;Nutrient;old mice;Operative Surgical Procedures;Osteoblasts;Osteogenesis;Pain;pain behavior;pain relief;Parathyroid Hormone Receptor;Pathologic;Patients;Permeability;Persons;Pharmaceutical Preparations;Phenotype;Physical activity;Physicians;Physiologic Ossification;Play;Population;Porosity;Process;Property;PTH gene;Quality of life;Rejuvenation;remediation;Replacement Arthroplasty;Reporter;Reporting;Risk;Role;Scientist;Sclerosis;Sensory;Signal Pathway;Signal Transduction;Skeleton;soft tissue;solute;Spinal;Spinal Fusion;Spinal Ganglia;spine bone structure;Structural defect;Structure;symptom treatment;symptomatology;System;Thick;Thinness;Translations;transmission process;Vacuole;Validation;vertebra body;Vertebral column

PROJECT_TITLE: PTH Attenuation of Spinal Degeneration During Aging PI Janet Crane


ORG_CITY: SAN ANTONIO

ORG_NAME: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM

ORG_STATE: TX

PHR: Discharged members of the US Armed Services are at increased risk of metabolic disease including type 2 diabetes. Hepatic insulin resistance plays a key role in this metabolic dysfunction and is a significant long-term healthcare issue to the VHA due to increased risk of developing additional pathologies and mortality. A key player in the development of hepatic insulin resistance is mechanistic target of rapamycin complex 1 (mTORC1) due to its ability to regulate lipid metabolism. Our preliminary data suggests that mTORC1 also plays a divergent role in the catabolism of unsaturated fatty acids leading to an overall hypothesis that mTORC1 regulates the ability of mitochondria to shift fatty acid substrate preference through catabolism of these fatty acids and that dysfunction in this pathway leads to hepatic insulin resistance. Our rationale for this study is that delineating the mechanisms of nutrient usage regulation by the liver will serve as a means to define new therapeutic targets for treatment and prevention of metabolic disease in our Veterans.

PI_NAMEs: SALMON, ADAM  (contact)

PROJECT_TERMS: Acyl Coenzyme A;Address;Affect;Animals;Automobile Driving;Biogenesis;Catabolism;Cell Culture Techniques;Cells;Coenzyme A;Complex;cost;Data;Defect;Development;Diet;Diet Modification;dietary;Dietary Fats;Dietary Fatty Acid;Enzymes;Etiology;Fatty acid glycerol esters;fatty acid metabolism;fatty acid oxidation;Fatty Acids;flexibility;FRAP1 gene;Functional disorder;functional outcomes;Genetic;genetic manipulation;glucose production;Goals;Health;Healthcare;Hepatic;Hepatocyte;Homeostasis;Impairment;improved;Insulin;Insulin Resistance;insulin sensitivity;insulin signaling;Knockout Mice;Link;lipid biosynthesis;lipid metabolism;Liver;Liver Mitochondria;Mediating;Mediator;member;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolic stress;Metabolism;Mitochondria;Morphology;mortality;mouse model;Mus;mutant mouse model;new therapeutic target;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;novel;Nutrient;Nutrient availability;Nutritional;Outcome;oxidation;Oxidoreductase;Pathology;Pathway interactions;Patients;Pharmacologic Substance;pi bond;Play;preference;Prevalence;prevent;Prevention;Primary carcinoma of the liver cells;Process;Regulation;Research;response;Risk;Role;saturated fat;Saturated Fatty Acids;Services;Signal Transduction;Source;Testing;Tissues;Unsaturated Fats;Unsaturated Fatty Acids;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: mTOR-Mediated Desaturation of Fatty Acids in Hepatic Insulin Resistance.


PHR: We do not understand what causes type 2 diabetes, but defects in the pancreatic islet and insulin secretion play a major role. Much of our knowledge has come from studies of rodent cells or rodents with diabetes, but this is problematic because human islets have critical differences from rodent islets. In this grant, we will use new technologies and experimental approaches to genetically manipulate non-diabetic, human islets to understand factors that effect their normal function. We will also study islets from individuals with type 2 diabetes to understand how common treatment improves the function of these diseased islets.

PI_NAMEs: POWERS, ALVIN C (contact)

PROJECT_TERMS: Affect;Agonist;Alpha Cell;Beta Cell;Binding;Cell Physiology;Cells;ChIP-seq;clinically actionable;clinically relevant;Color;common treatment;Data;Defect;Diabetes Mellitus;Disease;Environment;exenatide;Exposure to;Functional disorder;functional improvement;Gene Expression;Gene Expression Regulation;Gene Modified;gene product;Genes;genetic manipulation;Genetic Transcription;GLP-I receptor;Glucagon;glucagon-like peptide 1;glucose production;Grant;Healthcare Systems;Hepatic;Hormones;Human;human model;Hyperglycemia;immunodeficiency;Immunodeficient Mouse;Impairment;improved;In Vitro;in vivo;Individual;innovation;Insulin;Insulin Resistance;insulin secretion;Investigation;islet;Islet Cell;Islets of Langerhans;knock-down;Knockout Mice;Knowledge;Maintenance;Modeling;Molecular;mouse model;Mus;new technology;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;Paracrine Communication;Pathogenesis;Play;Process;Production;Rodent;Rodent Model;Role;Sampling;single cell sequencing;small hairpin RNA;System;Testing;transcription factor;transcription regulatory network;Transcriptional Regulation;transcriptome;Transplantation;Veterans

PROJECT_TITLE: Islet alterations in type 2 diabetes


PHR: Project Narrative Streptococcus agalactiae or Group B Streptococcus (GBS) is a bacterium that can cause invasive infections in pregnant hosts. This translational research seeks to understand how the toxicant exposure alters host susceptibility to infection and contributes to disease progression by modulating the host immune system. This knowledge may lead to new approaches for the prevention and treatment of reproductive tract infections which often lead to preterm birth, neonatal sepsis, maternal bacteremia, and fetal demise as well as ameliorate fertility issues associated with toxicant exposure.

PI_NAMEs: GADDY, JENNIFER A (contact)

PROJECT_TERMS: Address;adverse pregnancy outcome;Affect;Afghanistan;Age;agent orange;Anti-Bacterial Agents;antimicrobial;Area;Bacteremia;Bacteria;Basic Science;Biological Response Modifiers;Birth;burn pit;carcinogenesis;Cause of Death;Cells;Cellular biology;Child;combustion product;Data;Developmental Process;Diagnostic;Dioxins;Disease Outcome;Disease Progression;DNA;Endocrine Disruptors;Environment;Environmental Pollutants;environmental stressor;Exposure to;extracellular;Female;female fertility;Fertility;fetal;Fiber;Fire - disasters;Generations;Gravid;Growth;Homeostasis;host microbiota;Human;Immobilization;Immune;Immune response;Immune system;Immune System Diseases;immune system function;Immunologics;Impairment;improved;improved outcome;in utero;Infection;Inflammation;Inflammatory;Intervention;intraamniotic infection;Invaded;Iraq;Knowledge;Link;Macrophage;Maintenance;male;male fertility;Maternal-Fetal Exchange;Matrix Metalloproteinases;Membrane;Military Personnel;Modeling;Molecular;Mothers;mouse model;NADPH Oxidase;Natural Immunity;neonatal sepsis;novel strategies;Oils;organ on a chip;Outcome;pathogen;Peptides;Placenta;Play;Population;pre-clinical;Predisposition;Pregnancy;pregnant;Premature Birth;Prevention approach;Production;programs;Publishing;Reactive Oxygen Species;Recording of previous events;Reporting;Repression;reproductive;Reproductive Health;reproductive outcome;Reproductive Process;reproductive tract;Reproductive Tract Infections;Research Proposals;response;Risk;Role;Streptococcal Infections;Streptococcus Group B;Tetrachlorodibenzodioxin;Therapeutic Intervention;Tissues;Toxic Environmental Substances;toxicant;Toxicant exposure;Translational Research;Veterans;Vietnam;Woman

PROJECT_TITLE: Toxicant Exposure Impacts Host-pathogen interactions within the Reproductive Tract


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

PI_NAMEs: WHEELER, STEPHANIE BROOKE (contact)

PROJECT_TERMS: Address;Advocate;anti-cancer research;Cancer Burden;cancer care;Cancer Center;Cancer Center Support Grant;Cancer Control;cancer health disparity;Cancer Patient;cancer prevention;care delivery;Caregivers;Catchment Area;Clinical;clinical care;Clinical Trials;Communication;Communities;community advisory board;community engagement;Community Health;community organizations;Community Outreach;community partnership;Comprehensive Cancer Center;County;demographics;design;Development;Disparity;Doctor of Philosophy;Ensure;Equity;ethnic minority;Ethnic Origin;Ethnic Population;Evaluation;evidence base;experience;Face;Health Educators;Hispanic;Hospitals;Improve Access;improved;Infrastructure;Institution;investigator training;Malignant Neoplasms;Medicaid;medically underserved population;Mission;Monitor;Morbidity - disease rate;mortality;NCI Center for Cancer Research;North Carolina;Oncology;Outcome;outreach;patient engagement;Patients;Persons;Policies;Policy Maker;Population;Population Heterogeneity;Population Sciences;Population Sizes;Provider;Public Health;Race;racial diversity;racial minority;Recording of previous events;Reporting;Research;Research Support;Resources;Rural;rural counties;Rural Population;rurality;Specialist;success;Supportive care;synergism;telehealth;UNC Lineberger Comprehensive Cancer Center;Vision;Work

PROJECT_TITLE: Community Outreach and Engagement


ORG_CITY: MATHER

ORG_NAME: VA NORTHERN CALIFORNIA HEALTH CARE SYS

PHR: The past two decades have seen a high respiratory health burden for military personnel returning from deployments in Afghanistan and Iraq. Veterans have developed a variety of respiratory symptoms and been newly diagnosed with chronic obstructive pulmonary disease, asthma, and constrictive bronchiolitis. Environmental exposures including volatile organic compounds (VOCs) and particulate matter from burn pits, oil field fires, and metal alloys are thought to be causes; however, it has been challenging to concurrently measure and associate health metrics with environmental exposures. Breath testing of exhaled VOC biomarkers has the potential to transform healthcare for veterans in this regard. This project will bring a suite of portable sensors forward into development and clinical testing with the aim of identifying breath VOC signatures of exposures and help establish a “personalized exposure and medicine” platform for veterans.

PI_NAMEs: HARPER, RICHART W;KENYON, NICHOLAS J. (contact)

PROJECT_TERMS: active duty;Address;Adverse effects;Afghanistan;Air Pollutants;airway epithelium;Alloys;Area;Asia;Asthma;asthma prevention;asthmatic;asthmatic patient;biobank;Biological Markers;biomarker discovery;biomarker validation;Breath Tests;Bronchiolitis;burn pit;California;Cell Culture Techniques;Cells;Chronic Obstructive Pulmonary Disease;Clinic;Clinical Research;cohort;combustion product;Data;Development;Devices;Disease;Disease Management;disease phenotype;Down-Regulation;Eicosanoids;Engineering;Enrollment;Environmental Exposure;Environmental Science;epidemiology study;Epithelial Cells;Epithelium;Equipment and supply inventories;Exhalation;experimental study;Exposure to;Fire - disasters;Funding;Goals;Health;Healthcare;Healthcare Systems;Human;human tissue;improved;In Vitro;in vivo;Inflammatory;Iraq;Laboratories;Lung;Lung Diseases;Mass Spectrum Analysis;Measures;Mediating;Medicine;metabolomics;Metals;Methods;Military Personnel;mobile sensor;Monitor;Newly Diagnosed;novel;Oils;Particulate;Particulate Matter;Pathway interactions;Patients;personalized medicine;Physical condensation;pilot test;Population;portability;portable monitoring;Positioning Attribute;Prevention;pulmonary function;Recording of previous events;Research;research clinical testing;Research Personnel;research study;Respiratory Disease;respiratory health;Respiratory Signs and Symptoms;Risk;Sampling;sensor;Site;Soldier;Source;System;Technology;Time;tool;toxicant;Tracheobronchial;Up-Regulation;Veterans;volatile organic compound

PROJECT_TITLE: Defining Breath VOC Biomarkers to Improve Respiratory Health of Exposed Veterans


ORG_CITY: White River Junction

ORG_NAME: WHITE RIVER JUNCTION VA MEDICAL CENTER

ORG_STATE: VT

PHR: HIV-1 infects cells by binding to the CD4 and the CCR5 receptors on target cells. If a cell lacks either receptor, it is unlikely that it can be infected by most strains of HIV-1. Interestingly, some individuals have a mutation in the gene that encodes the CCR5 receptor, and are unable to become infected with certain strains of HIV-1. Developing methods to induce this mutation, called the CCR5-delta 32 mutation, in the stem cells of HIV-1 infected patients who do not have the mutation would potentially allow them to stop taking anti-retroviral medications without suffering any negative effects. We propose to develop a method that replaces the normal CCR5 gene with one carrying the CCR5-delta 32 mutation into stem cells using a newly discovered enzyme called CasX. We will also determine how many stem cells carrying two copies of the mutation are needed for an HIV-1 patient to stop taking anti-retroviral medications and still maintain a healthy immune system.

PI_NAMEs: HOWELL, ALEXANDRA L (contact)

PROJECT_TERMS: Adaptive Immune System;Alleles;Anti-Retroviral Agents;antiretroviral therapy;Area;Autologous;Autologous Transplantation;Bacteria;Bacteriophages;base;Binding;CCR5 gene;CD4 Positive T Lymphocytes;Cell surface;Cell Transplantation;Cells;Cellular Immunity;Clinical Research;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Communicable Diseases;Complex;Data;Derivation procedure;Development;DNA;DNA annealing;DNA Repair;DNA Sequence;endonuclease;Enzymes;Eukaryotic Cell;Event;Excision;Family;Flow Cytometry;gene editing technology;gene transplantation for gene therapy;gene-editing approach;Generations;Genes;Genetic Diseases;Genomic DNA;Goals;Guide RNA;Hematopoietic stem cells;Hepatitis B Infection;HIV;HIV Infections;HIV resistance;HIV-1;Hot Springs;Human;human disease;Human Genome;human pathogen;Humoral Immunities;hydraulic fracturing;Immune;Immune system;Immunodeficient Mouse;In Vitro;in vivo;Individual;Induced Mutation;Infection;Infusion procedures;innovation;Integrase;interest;Interruption;Isoptera;Lentivirus;Location;Malignant Neoplasms;mathematical model;Measures;Mediating;metagenomic sequencing;Metagenomics;Methods;Mus;mutant;Mutation;next generation;next generation sequencing;novel;nuclease;Null Lymphocytes;patient subsets;Patients;peripheral blood;Pharmaceutical Preparations;Phenotype;preclinical study;Process;Puromycin;receptor;Recombinants;resistance allele;Ribonucleoproteins;RNA;Single-Stranded DNA;Site;Sorting;Specificity;stem cells;System;Technology;Therapeutic;Time;tool;trial planning;Umbilical Cord Blood;Validation;Viral Genome;Viral Vector;Water

PROJECT_TITLE: Developing novel CRISPR/CasX editors to generate a CCR5/null immune system


ORG_CITY: PALO ALTO

ORG_NAME: VETERANS ADMIN PALO ALTO HEALTH CARE SYS

PHR: Self-tolerance and immune homeostasis are critical in suppressing excessive immune responses and autoimmune disease. Regulatory T lymphocytes are known to limit immune responses and are important in several models of transplantation and autoimmunity. The goals of this proposal involve understanding the development and function of this important regulatory lineage that will be used to improve the care of veterans.

PI_NAMEs: MALTZMAN, JONATHAN S (contact)

PROJECT_TERMS: Address;Adoptive Transfer;Autoantibodies;Autoimmune;Autoimmune Diseases;Autoimmunity;Caring;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Cellularity;clinically relevant;Data;Development;disease model;DNA Binding;Exhibits;Experimental Autoimmune Encephalomyelitis;Family;Family member;FOXP1 gene;FOXP3 gene;Gene Expression;Gene Expression Regulation;Generations;Genes;Genetic Transcription;Goals;Heart Transplantation;Hematopoietic System;Heterodimerization;High-Throughput Nucleotide Sequencing;Homeostasis;Homo;Human;Immune;Immune response;Immune Tolerance;Immunosuppression;Impairment;improved;in vivo;in vivo evaluation;in vivo Model;Inflammatory Bowel Diseases;Lead;Lymphocyte;Lymphocyte Activation;Lymphocytic Infiltrate;Lymphoid Tissue;Maintenance;Mediating;member;Modeling;Molecular;Mouse Strains;Mus;Mutation;novel;Organ;Organ Transplantation;Peripheral;Phenotype;Population;premature;Production;Regulation;Regulatory T-Lymphocyte;Role;Self Tolerance;Solid;System;T-Cell Development;T-Lymphocyte;T-Lymphocyte Subsets;Technology;Testing;Thymus Gland;transcription factor;translational approach;transplant model;Transplantation;Validation;Veterans

PROJECT_TITLE: Foxp transcription factors in regulatory T cells


ORG_CITY: COLUMBIA

ORG_NAME: HARRY S. TRUMAN MEMORIAL VA HOSPITAL

ORG_STATE: MO

PHR: This work is relevant to the VA mission in that we are developing new ways to target and treat aggressive forms of breast and prostate cancer that become resistant to standard treatment. We have obtained peptides and antibody fragment probes that bind to the lectin galectin-3 and its carbohydrate ligand Thomsen Friedenreich, and CD44v6 expressed on aggressive/cancer stem cells. These antigens function in key steps in tumorigenic pathways including cell adhesion, signaling, and immune response. Highly novel click chemistries and nanoparticles will be employed to generate multivalent/fluorescent/radiolabeled peptides and Abs to detect aggressive tumors, reduce tumor growth, and increase immune response in vivo. In terms of human health, the probes will improve the standard of care of patients in that they will be well tolerated in humans and radioactive versions will rapidly clear the body avoiding radiation damage. Our studies coincide with VA Healthcare Initiatives employing cancer biology, genomics and women's health issues.

PI_NAMEs: DEUTSCHER, SUSAN L;SMITH, CHARLES J (contact)

PROJECT_TERMS: Affinity;angiogenesis;Antibodies;Antigens;Bacteriophages;Binding;Biological Markers;Blood;Breast;Breast Cancer therapy;Cancer Biology;Cancer Detection;cancer imaging;cancer stem cell;cancer therapy;cancer type;Carbohydrates;CD44 gene;Cell Adhesion;Cells;Cessation of life;checkpoint receptors;Chelating Agents;Chemistry;Chemotherapy and/or radiation;Circulation;Clinical Trials;Combined Modality Therapy;Complex;Coupled;cycloaddition;Cyclooctenes;Detection;Development;Diagnosis;Disease;Dose;Dose Limiting;Drug Kinetics;Drug resistance;erbB-2 Receptor;Estrogens;Excretory function;Exhibits;Female;Galectin 3;Gender;General Population;Genomic medicine;Genomics;glycosylation;Goals;Health;Healthcare;Hormones;Human;Hydrophobicity;Image;imaging agent;immune checkpoint;Immune checkpoint inhibitor;Immune response;immunogenic;Immunoglobulin Fragments;Immunologic Surveillance;immunoregulation;improved;in vivo;Incidence;Injections;interest;irradiation;Kidney;Label;Laboratories;Lectin;Ligands;Malignant Breast Neoplasm;Malignant neoplasm of prostate;Malignant Neoplasms;Mammary Neoplasms;Metals;military veteran;Mission;Molecular;Morbidity - disease rate;Multimodal Imaging;multimodality;nanoparticle;near infrared dye;Neoplasm Metastasis;neoplastic cell;Normal tissue morphology;novel;Nucleosome Core Particle;Organ;overexpression;Pathway interactions;Patient Care;Patients;Peptide Fragments;Peptides;Phage Display;Population;Process;Progesterone;Prognosis;programmed cell death protein 1;Prostate;Protein Engineering;Radiation induced damage;Radiation therapy;Radioactive;Radioactivity;Radiochemistry;Radioimmunoconjugate;Radiolabeled;radiotracer;Reaction;Receptor Inhibition;Relapse;Research;Resistance;RNA Splicing;scaffold;Signal Pathway;Signal Transduction;Silicon Dioxide;small molecule;standard care;standard of care;stem cell biomarkers;success;Surface;T-Cell Receptor;targeted agent;targeted imaging;targeted treatment;theranostics;Therapeutic;Tissues;Toxic effect;triple-negative invasive breast carcinoma;tumor;tumor growth;tumorigenesis;tumorigenic;Tumorigenicity;United States;uptake;Variant;Veterans;Woman;Women's Health;Work

PROJECT_TITLE: Phage Display for Improved Peptide-Based Tumor Targeting and Imaging Agents