ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Neural stem cells (NSCs) hold promise for the treatment of neurological disorders common to our Veteran population such as traumatic brain injury and Parkinson’s disease. Understanding the molecular mechanisms by which NSCs differentiate into specific types of neurons and glia is key to unlocking their therapeutic potential. Our overall goal is to determine the molecular mechanisms that regulate NSC biology. For NSCs to make neurons, daughter cells need to express certain sets of genes while repressing others. Such lineage- specific gene expression is in part regulated by chromatin structure – the “packaged” state of DNA. We plan to use cell biology and molecular approaches to investigate how a specific chromatin regulator called MLL1 coordinates the production of specific types of neurons from NSCs.

PI_NAMEs: LIM, DANIEL A (contact)

PROJECT_TERMS: Adult;Architecture;autism spectrum disorder;Award;Biology;Brain;Cell Therapy;Cell Transplantation;cell type;Cellular biology;Chromatin;Chromatin Loop;Chromatin Structure;Data;daughter cell;Development;developmental disease;DNA;Dorsal;drug development;drug discovery;Enhancers;Epigenetic Process;forgetting;Gene Expression;Generations;Genes;Genetic Transcription;Genomics;Goals;Higher Order Chromatin Structure;histone modification;Human;human stem cells;insight;Intellectual functioning disability;interest;Knowledge;Maintenance;member;Memory;Methods;military veteran;Mixed-Lineage Leukemia;MLL gene;Molecular;Mutation;nerve stem cell;Nervous System Disorder;neural;neurodevelopment;neurogenesis;Neuroglia;Neurons;neuroregulation;Parkinson Disease;Play;Population;postnatal;Production;programs;Publishing;Regulatory Element;Repression;Role;Source;stem cell biology;stem cell differentiation;stem cell population;subventricular zone;Syndrome;System;Therapeutic;transcriptome;Translational Research;transplantation therapy;Traumatic Brain Injury;Ventricular;Veterans;Work

PROJECT_TITLE: Chromatin-based regulation of neural stem cells


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: Veterans Affairs

ORG_CITY: CHICAGO

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: JESSE BROWN VA MEDICAL CENTER

ORG_STATE: IL

PHR: Diarrhea in IBD is the result of impaired fluid and electroneutral NaCl absorption and remains a major health challenge to our veteran patient population. Dysregulation of DRA, the predominant protein involved in Cl- absorption, has been implicated in the pathophysiology of IBD-associated diarrhea. Therefore, increase in DRA expression and function is essential for enhancing Cl- absorption and exerting antidiarrheal effects. Of note, DRA also plays a key role in maintenance of epithelial barrier integrity. In this regard, glucocorticoids (GC), the first line therapeutics in IBD, are known to exert anti-inflammatory, barrier protective and proabsorptive effects. Our proposed studies are aimed at elucidating the molecular mechanisms involved in a novel finding of GC-mediated upregulation of DRA function and expression in physiological and inflammatory states. Outcome of these studies should establish that GC-mediated increase in DRA expression can alleviate the IBD associated diarrhea and barrier dysfunction.

PI_NAMEs: DUDEJA, PRADEEP K (contact)

PROJECT_TERMS: 3-Dimensional;absorption;Affect;Animal Model;Anions;Anti-Inflammatory Agents;Antidiarrheals;Antiinflammatory Effect;Apical;apical membrane;Bicarbonates;Binding;Biopsy;Caco-2 Cells;Cell Culture Techniques;Chlorides;Chronic;cohort;Colitis;Crohn's disease;Data;debilitating symptom;Defect;design;Dexamethasone;dextran sulfate sodium induced colitis;Diarrhea;Digestive System Disorders;Disease;Disease remission;Dose;Down-Regulation;Electrolytes;Epithelium;Exhibits;Functional disorder;Gene Expression;Genetic Transcription;genome wide association study;Glucocorticoid Receptor;Glucocorticoids;gut dysbiosis;gut inflammation;Health;healthcare burden;Human;immunoregulation;Impairment;improved;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Bowel Diseases;interest;Intervention;intestinal barrier;Intestinal permeability;Intestines;Investigation;Knockout Mice;Knowledge;Light;Link;Liquid substance;Maintenance;Measurement;Mediating;Messenger RNA;Molecular;monolayer;Morbidity - disease rate;mouse model;Mucositis;Mus;new therapeutic target;NF-kappa B;novel;novel therapeutic intervention;operation;Outcome Study;Pathogenesis;Pathway interactions;patient population;Patients;Phenotype;Physiological;Play;promoter;protein expression;Proteins;Quality of life;receptor;Recurrence;Regulation;Regulatory Element;Remission Induction;response;restoration;Role;Route;SLC26A3 gene;Sodium;Symptoms;T cell therapy;Therapeutic;Therapeutic Agents;Time;TNF gene;tool;Transcriptional Activation;Transcriptional Regulation;Ulcerative Colitis;Up-Regulation;Veterans;Water;Water Movements

PROJECT_TITLE: Mechanisms of Regulation of Intestinal Cl Absorption in IBD Associated Diarrhea


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Congenital Structural Anomalies;Genetics;Human Genome;Lymphatic Research;Pediatric;Prevention;Rare Diseases;Women's Health Research

ORG_CITY: CINCINNATI

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: Project Narrative  Our knowledge about the mechanisms controlling the progression from benign lymphatic malformation (LM) to the highly malignant lymphangiosarcoma (LAS) is very limited, and LAS remains as a deadly disease with no effective treatment at present. The characterization of both positive and negative signaling pathways and cellular processes that regulate LM progression to LAS will significantly advance our fundamental knowledge of the disease process and contribute to novel therapies for the prevention and treatment of LAS.

PI_NAMEs: GUAN, JUN-LIN  (contact)

PROGRAM_OFFICER_NAME: SCHRAMM, CHARLENE A

PROJECT_TERMS: Ablation;Adult;angiogenesis;autocrine;Autocrine Communication;Autophagocytosis;Benign;Blood Vessels;Breast Cancer Patient;Candidate Disease Gene;Cell model;Cell Physiology;Cell Proliferation;Cells;Childhood;Chronic;conditional knockout;CRISPR screen;CRISPR/Cas technology;Cytoplasm;Data;design;Development;Disease;Disease Progression;ECM receptor;effective therapy;efficacy evaluation;Endothelial Cells;follow-up;Functional disorder;Funding;Future;Gene Expression Profiling;Genes;genetic approach;genome-wide;Goals;Human;In Vitro;in vivo;Infant;inhibition of autophagy;Integrins;knock-down;Knock-in Mouse;Knock-out;Knockout Mice;Knowledge;Lymphangiogenesis;lymphangiosarcoma;lymphatic development;Lymphatic Endothelial Cells;lymphatic malformations;lymphatic vessel;Lymphedema;Lysosomes;malformation;Malignant - descriptor;Malignant Neoplasms;MAP Kinase Gene;MAPK Signaling Pathway Pathway;Mediating;Modeling;Molecular;mouse model;Mus;Neoplasms in Vascular Tissue;neoplastic cell;novel therapeutics;osteopontin;Pathway interactions;patient derived xenograft model;patient responsibilities;Patients;pharmacologic;Play;Prevention;Prevention therapy;Process;Proliferating;Radical Mastectomy;ras GTPase-Activating Proteins;Ras Signaling Pathway;receptor;Recycling;Regulation;Risk Factors;Role;Signal Pathway;Signal Transduction;small hairpin RNA;synergism;trafficking;transcriptome sequencing;TSC1 gene;tumor;Tumor Cell Line;tumor growth;Tumor Promotion;Tumor Suppressor Genes;Tumorigenicity

PROJECT_TITLE: Mechanisms of progression of vascular malformation to lymphangiosarcoma

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Asthma;Bioengineering;Health Effects of Indoor Air Pollution;Lung;Nanotechnology

ORG_CITY: RALEIGH

ORG_DEPT: BIOLOGY

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

ORG_STATE: NC

PHR: Public Health Relevance Engineered nanoparticles, including multi-walled carbon nanotubes (MWCNTs), have numerous applications in industry and consumer products, yet pose potential human health risks upon inhalation exposure; of particular relevance to public health are our recent studies in rodents that show severe exacerbation of allergen-induced lung inflammation and fibrosis by MWCNTs. The goal of our proposed research project is to explore basic mechanisms through which MWCNTs interact with common allergens to produce chronic airway disease in mice and further elucidate mechanisms using cultured human and mouse pulmonary cells. The results of these studies will benefit public heath by identifying basic mechanisms through which nanoparticles cause human respiratory disease and discovering molecular targets that could be exploited for therapeutic treatment of chronic airway disease.

PI_NAMEs: BONNER, JAMES CHRISTOPHER (contact)

PROGRAM_OFFICER_NAME: RAVICHANDRAN, LINGAMANAIDU V

PROJECT_TERMS: Adsorption;Airway Disease;Airway Fibrosis;airway hyperresponsiveness;Allergens;Allergic;allergic airway disease;Amines;Area;Artificial nanoparticles;Asthma;Binding;Biological;Biological Assay;Bronchial Spasm;Cell Communication;Cell surface;cell type;Cells;chemical addition;chemical group;Chronic;chronic respiratory disease;consumer product;cytokine;Data;design;Disease;double walled carbon nanotube;Environment;eosinophilic inflammation;Exposure to;Extrinsic asthma;G-Protein-Coupled Receptors;Genetic Predisposition to Disease;Goals;hazard;Health;House Dust Mite Allergens;Human;Immune;In Vitro;Industry;Inflammation;Inhalation;Inhalation Exposure;inhibitor;Interferons;Knock-out;Knockout Mice;Knowledge;Libraries;Lung;Lung Diseases;Macrophage;Mediating;Metaplasia;Molecular Target;Mucous body substance;Mus;nanoparticle;novel;PAR-2 Receptor;Pathology;Phenotype;Predisposition;Process;profibrotic cytokine;Property;Proteins;Proteomics;Public Health;public health relevance;Pulmonary Fibrosis;Pulmonary Inflammation;Pyroglyphidae;Reporting;Research Project Grants;Respiratory Disease;response;Risk;Rodent;Rodent Model;Role;Serine Protease;Signal Transduction;STAT1 gene;STAT3 gene;STAT6 gene;Surface;Testing;Therapeutic;transcription factor;Wild Type Mouse;Work

PROJECT_TITLE: Mechanisms of Nanoparticle Modulation of Allergic Lung Disease

STUDY_SECTION: SIEE

STUDY_SECTION_NAME: Systemic Injury by Environmental Exposure[SIEE]


ORG_CITY: CHARLESTON

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

ORG_STATE: SC

PHR: The application will fill a critical knowledge gap in our understanding of RAS family GTPases which play a central role in many aspects of biology including growth, differentiation, and development. The medical importance of RAS is highlighted by its frequent mutational activation in ~30% of human cancers with pancreatic cancers harboring RAS mutations in >90% of tumors. We have discovered a paradigm shifting approach to therapeutically inhibit RAS signaling and oncogenic transformation through targeting nucleotide- free RAS (apoRAS). Completion of these studies will provide fundamental support for development of therapeutics targeting apoRAS. Thus, this work has tremendous translational significance and relevance for Veterans who are disproportionately impacted by RAS-mutant cancers. We anticipate that these studies will lead to the future development of small molecules RAS inhibitors that specifically target apoRAS.

PI_NAMEs: O'BRYAN, JOHN P (contact)

PROJECT_TERMS: Address;Affinity;Antibodies;Automobile Driving;Award;Binding;Binding Proteins;Biochemical;Biological Models;Biological Products;Biology;Cancer Patient;Cells;cellular targeting;Chemicals;Clinic;Clinical Trials;Cytoplasm;Data;Development;Dimerization;Disease;Dissociation;efficacy evaluation;Environment;Equilibrium;Exhibits;Family;Family member;FDA approved;Future;General Population;Growth;GTP Binding;Guanosine Triphosphate;Guanosine Triphosphate Phosphohydrolases;Health;Human;In Vitro;in vivo;Incidence;inducible gene expression;inhibitor;innovation;insight;Knowledge;KPC model;KRAS oncogenesis;KRAS2 gene;KRASG12D;Maintenance;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Medical;Methods;military veteran;mimetics;Modeling;mouse model;multidisciplinary;mutant;Mutate;Mutation;N-ras Genes;nanocluster;novel;novel strategies;Nucleotides;Oncogenic;Organoids;Pancreatic Ductal Adenocarcinoma;pancreatic neoplasm;patient derived xenograft model;Patients;Pharmaceutical Preparations;pharmacologic;PIK3CG gene;Play;pre-clinical;Prevalence;prevent;Protac;Proteins;Proto-Oncogene Proteins c-akt;RAS inhibition;Ras Inhibitor;ras Proteins;Reagent;Reporting;Research;Role;Signal Transduction;small molecule;Specificity;Sulfhydryl Compounds;targeted treatment;Technology;Therapeutic;therapeutic development;therapeutic target;three dimensional cell culture;tool;Transgenic Organisms;Translations;tumor;tumorigenesis;Veterans;Work;Xenograft procedure

PROJECT_TITLE: Novel Functions for Ras family GTPases


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

ORG_STATE: CA

PHR: Six million people in the US have heart failure and 550,000 new cases are diagnosed annually. Despite current optimal therapy, there are 300,000 deaths every year in the US due to heart failure. Among these 6 million patients, 3 million have heart failure with normal ejection fraction, a measure of the heart’s ability to pump blood. However, conventional therapies, which have been shown to reduce mortality in patients with heart failure with reduced ejection fraction, fail to reduce mortality in patients with heart failure with normal ejection fraction. Because the prevalence of heart failure with normal ejection fraction is increasing, and outlook is dismal, we need new treatments. We propose, based on studies performed in the previous tenure of our VA Merit award, that intravenous delivery of a virus vector encoding the protein urocortin 2 is a promising approach for these patients. The proposed work will test this in rat and mouse models of heart failure with normal ejectionfraction, determine mechanisms, and test related proteins such as urocortin 3.

PI_NAMEs: HAMMOND, H. KIRK  (contact)

PROJECT_TERMS: Address;aged;Aging;Award;blood pump;Ca(2+)-Transporting ATPase;Cardiac;Cardiac Myocytes;cardiovascular effects;Cardiovascular system;Cessation of life;Clinical;clinical translation;Clinical Trials;conventional therapy;Corticotropin-Releasing Hormone Receptors;Dahl Hypertensive Rats;design;Development;Diagnosis;Disease;Effectiveness;effectiveness evaluation;EFRAC;Endocrine;Endoplasmic Reticulum;Exclusion;expression vector;Funding;Gene Transfer;Grant;Heart;Heart failure;heart failure with reduced ejection fraction;heart function;heart preservation;hospitalization rates;Hypertension;hypertensive;improved;in vivo;Intravenous;intravenous administration;Laboratories;Left;Left Ventricular Function;Life;Link;Maps;Measures;Medical;Membrane;Methods;Modeling;mortality;mouse model;Mus;novel therapeutics;old mice;optimal treatments;paracrine;Pathway interactions;Patients;Peptides;Persons;preclinical study;preservation;pressure;Prevalence;Proteins;Rattus;Risk Factors;Safety;Sarcomeres;Sarcoplasm;Series;Smooth Muscle;Testing;Time;transgene expression;Treatment Effectiveness;urocortin;Vascular Smooth Muscle;Vasodilation;Vasodilator Agents;vector;Ventricular;Veterans;Virus;Work

PROJECT_TITLE: Urocortin 2 Gene Transfer for Heart Failure with Preserved Ejection Fraction


ORG_CITY: RICHMOND

ORG_NAME: VA VETERANS ADMINISTRATION HOSPITAL

ORG_STATE: VA

PHR: Veterans have a high incidence of progression of heart failure requiring heart transplantation. Unfortunately, this life-saving treatment is not offered to all patients with end-stage heart failure due to limited heart donors. Up to 20% of veterans with end-stage heart failure die awaiting transplantation. An alternative source of organs already used for liver and kidney transplants are hearts from donors who have suffered circulatory death. These organs are currently used in experimental setup only due to the ischemic damage caused by the circulatory death process. We learned that mitochondrial permeability transition pore opening, and protease activation are principle mechanisms responsible for damage to the circulatory death heart. Our proposal will explore and harness novel pharmacologic mechanisms targeted at preventing mitochondrial permeability transition pore opening and proteases activation to rehabilitate circulatory death hearts.

PI_NAMEs: QUADER, MOHAMMED  (contact)

PROJECT_TERMS: Affect;Autologous Transplantation;Brain Death;Brain Injuries;Calcium;Calpain;Cardiac;Cardiac Death;CASP1 gene;Cause of Death;Cell Death Induction;Cessation of life;Clinical;Combined Modality Therapy;Coupling;Cyclosporine;Cytosol;Development;effectiveness study;Electron Transport;Eligibility Determination;Enzymes;Evaluation;experience;experimental study;Family suidae;follow-up;Funding;Generations;Goals;graft dysfunction;graft function;Heart;Heart failure;heart function;Heart Injuries;Heart Transplantation;Heterotopic Transplantation;Impairment;improved;In Situ;Incidence;Individual;Inflammation;inhibitor;Injury;Intervention;Ischemia;junctophilin;Kidney;Kidney Transplantation;Lead;Learning;Life;Liver;liver transplantation;Lung;mechanical circulatory support;Mediating;Mediator;Metabolism;Mitochondria;mitochondrial dysfunction;mitochondrial permeability transition pore;Modeling;Muscle Cells;Myocardial dysfunction;myocardial injury;Myocardial Ischemia;Myocardial Reperfusion Injury;Myocardium;novel;Organ;Patients;Peptide Hydrolases;Persons;pharmacologic;Play;porcine model;prevent;Process;protective effect;Protocols documentation;Rattus;Reactive Oxygen Species;Reperfusion Injury;Reperfusion Therapy;Research;Risk;Role;Solid;Source;Spectrin;Structural Protein;Testing;Time;translational potential;Transplantation;Veterans;Warm Ischemia;Work

PROJECT_TITLE: Reduction of cardiac injury in DCD hearts with prolonged ischemic period: Role of MPTP opening and calpain activation


ADMINISTERING_IC: TW

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Clinical Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurosciences;Social Determinants of Health

ORG_CITY: SEATTLE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: This proposal is to establish the Northern Pacific Global Health Leadership, Education, And Development for Early-career Researchers (NPGH LEADERs) Consortium – a research training program directed by the University of Washington in partnership with the Universities of Hawaii, Michigan and Minnesota with international partnerships in Cameroon, Ghana, India, Kenya, Liberia, Nepal, Peru, Thailand, and Uganda. The goal of this Consortium is to provide outstanding mentored research training to U.S. and LMIC post-doctoral and U.S. pre-doctoral trainees at international partner institutions in order to create the next generation of independent global health scientists and leaders.

PI_NAMEs: DATTA, DIBYADYUTI ;JOHN, CHANDY C.;MOYER, CHERYL A.;PRASAD, SHAILENDRA ;ZUNT, JOSEPH RAYMOND (contact)

PROGRAM_OFFICER_NAME: HAYES, UNJA

PROJECT_TITLE: Northern Pacific Global Health Leadership, Education, and Development for Early-career Researchers (NPGH LEADERs)


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Precision Medicine

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: As conventional tissue-based biomarkers are limited by availability, safety, and patient considerations, and most current blood-based biomarkers do not accurately assess tumor or immune microenvironment status, there is an urgent need to develop new biomarkers that not only aid in the choice, but also predict response to immunotherapy and other anti-cancer treatments. Recent studies suggest that cytotoxic T and natural killer cells isolated from peripheral blood mononuclear cells (PBMCs), may, if processed appropriately, provide a blood- based biomarker that could substitute for a routine biopsy and more closely reflect both the systemic and tumor immune response. The purpose of this proposal is to optimize the processing of these easily attainable blood samples and demonstrate that under these optimal conditions, they can be utilized as biomarkers and improve patient-specific treatment choices by predicting outcomes as a surrogate to, as well as complement, the standard tissue biopsy.

PI_NAMEs: DILLEHAY MCKILLIP, KELSEY ;WISE-DRAPER, TRISHA M (contact)

PROGRAM_OFFICER_NAME: RAO, ABHI

PROJECT_TERMS: Activities of Daily Living;Aftercare;anti-cancer treatment;Biological Assay;Biological Markers;biomarker development;Biopsy;Blood specimen;blood-based biomarker;cancer therapy;Cell Physiology;Cell Separation;Cell Survival;Cell-Mediated Cytolysis;Cells;Cellular Assay;Chemotaxis;Clinical;clinical decision-making;Clinical Treatment;Clinical Trials;Collaborations;Collection;Complement;cytokine;cytotoxic;Dependence;design;Detection;Development;DNA;Drug Targeting;flexibility;Flow Cytometry;functional outcomes;Future;Grant;head and neck cancer patient;Hematologic Neoplasms;Histology;Immune;immune function;Immune response;Immunohistochemistry;Immunotherapy;improved;individualized medicine;Infiltration;instrumentation;Knowledge;Malignant Neoplasms;Methods;Mission;Natural Killer Cells;new therapeutic target;novel;novel therapeutics;Ohio;outcome prediction;Pathway interactions;Patients;Peripheral;peripheral blood;Peripheral Blood Mononuclear Cell;predicting response;Prediction of Response to Therapy;prevent;Process;Protein Analysis;Protocols documentation;Reproducibility;Reproducibility of Results;Resistance;response;RNA;Safety;sample collection;Sampling;Science;Site;Solid Neoplasm;Source;Specimen;Stress;survival outcome;Techniques;Testing;Therapeutic;Time;Tissues;treatment choice;Treatment Efficacy;treatment response;Tube;tumor;tumor behavior;tumor microenvironment;Tumor Tissue;tumor-immune system interactions;Tumor-infiltrating immune cells;Universities;Validation;Whole Blood

PROJECT_TITLE: Optimization of peripheral blood mononuclear cell (PBMC) processing for robust downstream functional immune cell analysis and correlation with therapeutic efficacy


NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Genetics;Mental Health;Neurosciences;Pediatric;Prevention

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent psychiatric disorder, and a novel gene associated with ADHD is Latrophilin-3, however if environmental factors, such as pyrethroid exposure, interact with genetic factors to exacerbate this disorder is unknown. We developed a knock-out rat of Lphn3 that has abnormalities similar to ADHD (hyperactivity). We will test the combined effects of pyrethroids and Lphn3 knock-outs or heterozygous rats at different ages to elucidate whether this class of insecticides triggers or exacerbates ADHD-like effects in this model system.

PI_NAMEs: VORHEES, CHARLES V (contact);WILLIAMS, MICHAEL T

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: Acoustics;Adhesions;Adult;Affect;Age;alpha-latrotoxin receptor;Amygdaloid structure;Apoptosis;Attention deficit hyperactivity disorder;Behavioral;Binding;Biochemical;Biological;Biological Models;Brain region;Cell Adhesion;Cerebellum;Child;Corpus striatum structure;cost;Data;decamethrin;Development;Disease;Dopamine;Dose;Electrophysiology (science);Environment;environmental agent;Environmental Risk Factor;Exposure to;Extracellular Domain;FLRT3 gene;Functional disorder;G-Protein-Coupled Receptors;gene environment interaction;Genes;Genetic;Genetic Predisposition to Disease;genetic risk factor;Genotype;Heterozygote;Hippocampus;Home;Human;Hyperactivity;Impaired cognition;Insecticides;Knock-out;Learning;Membrane;Memory;Mental disorders;Modeling;morris water maze;N-Methylaspartate;Names;National Institute of Mental Health;neurobehavioral;neurochemistry;neuropsychiatric disorder;Neurotoxins;novel;novel strategies;null mutation;Occupational Exposure;Odds Ratio;Online Mendelian Inheritance In Man;Outcome;Permethrin;pesticide exposure;pesticide interaction;Pesticides;Phenotype;Population;postnatal;Predisposition;Prefrontal Cortex;prepulse inhibition;Prevalence;pyrethroid;Radial;Rattus;Risk Assessment;Risk Factors;risk variant;Rodent;Short-Term Memory;Stimulus;Susceptibility Gene;Symptoms;Tactile;Testing;Variant;water maze;Weaning

PROJECT_TITLE: Gene-pesticide interactions and ADHD

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ADMINISTERING_IC: DA

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Bioengineering;Drug Abuse (NIDA only);Neurosciences;Opioids;Pain Research;Substance Misuse

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Design of genetically encoded sensors for detecting endogenous opioid peptides Endogenous opioid signaling is highly complex and plays a role in pain reduction, euphoria, respiration, alcohol abuse, depression and stress response. It is critical to study when and where the endogenous opioid peptides are released at high spatiotemporal resolution to understand the endogenous opioid sig- naling. We propose to design two classes of opioid sensors for mapping and monitoring endogenous opioid peptide release, which will significantly advance the field and facilitate the design of pain medications with minimum side effects.

PI_NAMEs: WANG, WENJING  (contact)

PROGRAM_OFFICER_NAME: BERTON, OLIVIER

PROJECT_TERMS: addiction;Address;Adverse effects;Agonist;Alcohol abuse;Analgesics;Animal Model;Autopsy;Behavior;Biological;biological adaptation to stress;Brain;Brain region;brain tissue;brain volume;Cells;Central Nervous System;Complement;Complex;Constipation;design;Detection;detection method;Directed Molecular Evolution;endogenous opioids;Euphoria;Fluorescence;Genetic Transcription;Goals;Image Analysis;improved;in vivo;irradiation;Knowledge;Label;Light;Maps;Mental Depression;meter;Methods;Microdialysis;Monitor;mu opioid receptors;Mus;neural circuit;neuronal cell body;neuronal circuitry;Neurons;neuroregulation;novel;Opiate Addiction;Opioid;Opioid agonist;opioid epidemic;Opioid Peptide;Opioid Receptor;Pain;pain reduction;Pathologic Processes;Peptide Receptor;Peptide Signal Sequences;Peptides;Peripheral Nervous System;Pharmaceutical Preparations;Physiological Processes;Receptor Signaling;Regulation;Reporter;Resolution;Respiration;respiratory;response;Rewards;Role;sensor;side effect;Signal Transduction;Sleep;spatiotemporal;Specificity;Stimulus;System;temporal measurement;Time;tool;Virus Diseases

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


ORG_CITY: OMAHA

ORG_NAME: OMAHA VA  MEDICAL CENTER

ORG_STATE: NE

PHR: Potential Impact on Veterans Health Care: Obesity and aging are a major drivers of progressive diseases, including type 2 diabetes, cardiovascular disease, cancers, and degenerative disorders. The adult obesity rate in the USA is 39%, and an additional 32% are overweight, with an annual cost of $147 billion in the USA. In comparison, in veterans, the prevalence of obesity and overweight is 41% and 37%, respectively. At the same time, the median age of the veteran population (65 years) was higher than nonveterans (42 years), and the percentage of veterans aged 65 or older is projected to reach 50% of the total veteran population over the next 25 years. Both ageing and obesity are associated with dysfunction of the fat tissue, promoting increasing risk of developing diabetes. These studies will seek to understand how the hormone relaxin controls fat tissue health, and how it can be used to treat dysfunction caused by obesity and aging. Successful completion of the proposed research is expected to have a positive impact for veteran health care, a major part of the VA Mission.

PI_NAMEs: BENNETT, ROBERT G (contact)

PROJECT_TERMS: adipokines;adiponectin;Adipose tissue;adult obesity;Affect;Age;age related;Aging;Agonist;Biochemical;Brown Fat;Cardiovascular Diseases;Cells;combat;comorbidity;Conjugated Linoleic Acids;cost;Data;Degenerative Disorder;Development;Diabetes Mellitus;diet-induced obesity;disease model;effective therapy;Elements;Endocrinology;Environment;experience;experimental study;Fatty acid glycerol esters;Fibrosis;Functional disorder;Goals;Health;Healthcare;Hormones;human old age (65+);Hypoxia;Impairment;improved;in vivo;Inflammation;Injury;innovation;insight;Knockout Mice;Leptin;Lipids;Lipolysis;Liver;Liver Cirrhosis;Liver diseases;Liver Fibrosis;liver function;Liver Regeneration;Macrophage;Maintenance;Malignant Neoplasms;Metabolic Diseases;Metabolism;military veteran;Mission;Modeling;Mus;nanoparticle;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;Obesity;Obesity associated disease;Organ;Overweight;Pathway interactions;Population;PPAR gamma;Prevalence;Progressive Disease;Proteomics;receptor;Relaxin;relaxin receptor;Research;Risk;Role;Serum;Signal Pathway;Signal Transduction;subcutaneous;targeted delivery;Testing;Time;Tissues;translational approach;uptake;Veterans;Visceral;Work

PROJECT_TITLE: The Role of Relaxin Signaling in Adipose Tissue Fibrosis and Function


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Cancer;Prevention

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE This longstanding program is in its 40th year. It provides protected and mentored research training activities with the goal of preparing medical oncology physicians who will transform and advance the targeted treatment and prevention of cancer.

PI_NAMEs: ARMANIOS, MARY Y (contact);AZAD, NILOFER S.

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TERMS: Cancer Detection;cancer therapy;Molecular Target

PROJECT_TITLE: Molecular Targets for Cancer Detection and Treatment

STUDY_SECTION: NCI

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


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Lung;Nutrition;Obesity;Physical Activity

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE More than 80% of patients with heart failure with preserved ejection fraction (HFpEF) are obese and obesity is considered a primary comorbidity in HFpEF, yet, the role of obesity in provoking symptoms of dyspnea on exertion (DOE) and exercise intolerance in HFpEF patients has, thus far, been neglected. Obesity-related mechanical ventilatory constraints ultimately 1) increase the oxygen (O2) cost of breathing and 2) impose a mechanical ceiling on ventilation (V̇E) during exercise, which could provoke DOE and reduce exercise capacity. The overall aim of this K99/R00 proposal is to 1) investigate the O2 cost of breathing and examine how this impacts DOE and peak exercise capacity in patients with HFpEF, and 2) reduce obesity-related mechanical ventilatory constraints to potentially reduce DOE and increase exercise capacity in patients with HFpEF.

PI_NAMEs: BALMAIN, BRYCE  (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: Adult;Affect;Air;American;Breathing;Cardiovascular system;Chest;common symptom;comorbidity;cost;debilitating symptom;density;Dyspnea;EFRAC;Epidemic;Exercise;exercise capacity;exercise intolerance;Exercise Test;Exertion;Frequencies;functional improvement;Functional Residual Capacity;Gases;Goals;Heart failure;Helium;Human;Hyperpnea;Investigation;lung volume;Measures;mechanical load;Mechanics;National Heart, Lung, and Blood Institute;neglect;Non obese;novel therapeutic intervention;novel therapeutics;Obesity;Oxygen;Patients;Pattern;personalized medicine;Phase;Physiology;Population;preservation;Prevalence;pulmonary function;Recommendation;Respiratory Mechanics;Rest;Risk;Role;Symptoms;Testing;Therapeutic;Thinking;Tidal Volume;ventilation;Vital capacity;Work of Breathing;working group

PROJECT_TITLE: Targeting breathing limitations to improve functional outcomes in HFpEF

STUDY_SECTION: MTI

STUDY_SECTION_NAME: NHLBI Mentored Transition to Independence Study Section[MTI(JA)]


ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA CITY VA MEDICAL CENTER

ORG_STATE: OK

PHR: PROJECT NARRATIVE Hospitalization and the associated muscle loss with bedrest accelerate progression to disability in older Veterans. This proposal uses the rat hindlimb unloading model to determine if chronic mTOR activity impairs the recovery of muscle after disuse. It is expected that completion of this study will identify mechanisms and a new approach to minimize the loss of muscle mass/function in older Veterans during critical periods of disuse.

PI_NAMEs: MILLER, BENJAMIN FRANCIS (contact)

PROJECT_TERMS: Acceleration;Acute;Address;Adult;age acceleration;age related;aged;animal old age;Atrophic;Bed rest;Biochemical;Biology;CCI-779;Chronic;Chronic Disease;comorbidity;Contractile Proteins;critical period;Data;Deterioration;disability;Disability prevention;Disuse Atrophy;Essential Amino Acids;experimental study;Failure;Fibrosis;Fractionation;frailty;FRAP1 gene;Functional disorder;functional outcomes;General Population;Goals;Growth;Hindlimb Suspension;Histology;Hospitalization;Human;Image;Impairment;improved;Inbred BN Rats;innovation;Inpatients;Isotope Labeling;juvenile animal;Kinetics;Knowledge;Length of Stay;Maintenance;mechanotransduction;military veteran;Mitochondria;mitochondrial dysfunction;Mitochondrial Proteins;Modeling;Morphology;mRNA Translation;mTOR inhibition;mTOR Inhibitor;Muscle;muscle aging;muscle form;Muscle function;muscle strength;Muscular Atrophy;normal aging;novel;novel strategies;older adult;Older Population;Outcome;preservation;prevent;Procedures;protein degradation;Proteins;Proteomics;Rattus;Recording of previous events;Recovery;Recurrence;Resistance;Resolution;sarcopenia;secondary outcome;Signal Transduction;Sirolimus;Skeletal Muscle;skeletal muscle wasting;Spirometry;Stress;Tail;Testing;Tissues;Tracer;transcriptome sequencing;Translating;Veterans;Work

PROJECT_TITLE: Mechanism through which chronically elevated mTOR activity impairs aged muscle recovery after disuse atrophy


NIH_SPENDING_CATS: Aging;Biomedical Imaging;Chronic Obstructive Pulmonary Disease;Climate-Related Exposures and Conditions;Clinical Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Lung;Prevention;Social Determinants of Health

PHR: PROJECT NARRATIVE Today, persons living with HIV (PLWH) are faced with an increased burden of chronic respiratory disease, out of proportion to what would be expected by traditional risk factors. There remains a critical need to understand the drivers of the accelerated lung function decline and disease development in PLWH, including the potential role of the environment. This proposal examines the contribution of long-term air pollution exposure to accelerated lung aging and disease development among PLWH and whether HIV increases susceptibility to pollution exposure, in hopes of identifying a modifiable risk factor that can be targeted to improve lung health in this vulnerable population.

PI_NAMEs: RAJU, SARATH  (contact)

PROGRAM_OFFICER_NAME: MONGODIN, EMMANUEL FRANCK

PROJECT_TERMS: accelerated epigenetic aging;Acceleration;Address;Affect;age acceleration;age effect;Age related comorbidities;Aging;aging biomarker;aging mechanism;Air;Air Pollution;ambient air pollution;Award;Baltimore;Biological;Biological Aging;Biological Markers;career;career development;chest computed tomography;Chronic;Chronic Disease;chronic respiratory disease;cigarette smoke;Clinical;clinical care;cohort;Cohort Studies;Data;Development;Development Plans;Dimensions;Disease;Disease Marker;DNA Methylation;Early identification;Environment;Environmental Exposure;environmental health disparity;epigenetic aging;epigenetic clock;epigenetic marker;Epigenetic Process;Etiology;experience;Exposure to;Face;fine particles;Functional disorder;Funding;General Population;Goals;Health;health related quality of life;high risk population;HIV;HIV Infections;Household Air Pollution;Image;Impairment;improved;Individual;Inflammation;Infrastructure;Knowledge;Life Expectancy;Lung;Lung Diseases;lung health;Measurement;Measures;Mediating;Mentors;Mentorship;Methods;Modeling;modifiable risk;molecular marker;Nitrogen Dioxide;novel;Ozone;Parents;Participant;Persons;Phenotype;Physicians;Physiological;pollutant;Pollution;Population;Populations at Risk;Positioning Attribute;Predisposition;prospective;Prospective cohort;Pulmonary Emphysema;pulmonary function;pulmonary function decline;Quality of life;radiological imaging;Research;Resolution;Resources;Respiratory Disease;respiratory health;respiratory morbidity;response;Risk;Risk Factors;Role;Scientist;small airways disease;Techniques;Testing;Thoracic Radiography;tool;Training;training opportunity;translational study;Vulnerable Populations;X-Ray Computed Tomography

PROJECT_TITLE: Air Pollution's Impact on Lung Aging in HIV

STUDY_SECTION: MPOR

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


ADMINISTERING_IC: GM

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: Project Narrative The goal of this training program is to train science and engineering students in the fundamental principles underlying molecular machines, the enzymes, motors, switches, and pumps that power cell function. Students will be trained in structural biology, single-molecule biophysics, and computation, and additionally will learn how to create 3D molecular simulations. Trainees will be prepared for careers in interdisciplinary molecular biophysics research, industries such as pharmaceuticals or biomedical devices, teaching, or science policy positions.

PI_NAMEs: HANCOCK, WILLIAM OLAF (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TITLE: Molecular Machines Mechanism and Structure (M3S) Training Program

STUDY_SECTION: TWD

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


NIH_SPENDING_CATS: Biomedical Imaging;Cardiovascular;Chronic Obstructive Pulmonary Disease;Clinical Research;Lung;Pulmonary Hypertension

PHR: Project Narrative Pulmonary vascular disease commonly occurs in chronic obstructive pulmonary disease (COPD), and despite the increased morbidity associated with severe pulmonary vascular disease, there is limited understanding of the clinical implications of less severe pulmonary vascular disease. Understanding the contribution of early pulmonary vascular disease to COPD morbidity will define opportunities for targeted interventions of the pulmonary vasculature that could improve outcomes in COPD patients. As a necessary first step, this proposal will address key limitations in characterizing less severe PVD with multi-modal noninvasive approaches and apply these approaches to evaluate the contribution of pulmonary vascular disease to COPD morbidity across its observed spectrum of severity.

PI_NAMEs: BALASUBRAMANIAN, APARNA  (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: Address;Adult;Affect;Alveolar capillary destruction;Alveolus;American;Award;Biometry;Blood flow;Blood Vessels;Cardiac Catheterization Procedures;cardiac magnetic resonance imaging;Cardiology;career development;Caring;Chronic Obstructive Pulmonary Disease;Clinical;Clinical Trials;clinically relevant;cohort;Cohort Studies;comorbidity;Development;diagnosis standard;diagnostic accuracy;Diagnostic tests;Diffusion;Disease;Disease Management;Echocardiography;Environment;Epidemiology;Evaluation;Foundations;functional status;Funding;Future;Gases;Guidelines;health related quality of life;hemodynamics;Impairment;improved outcome;Individual;insight;Institution;International;Intervention;Knowledge;Longitudinal cohort;Longitudinal Studies;Lung;Lung Capacity;Magnetic Resonance Imaging;Measurement;Measures;Mentorship;Methodology;Modality;Morbidity - disease rate;mortality;Multicenter Studies;multidisciplinary;multimodality;novel;novel marker;Outcome;Participant;Patients;Physiological;Population;prevent;Procedures;prognostic;prospective;Prospective cohort;pulmonary arterial pressure;Pulmonary Hypertension;pulmonary vascular disorder;Pulmonary Vascular Resistance;Radiology Specialty;Recommendation;Recording of previous events;Research;Research Design;Research Personnel;Research Priority;Resources;respiratory morbidity;right ventricular failure;Right ventricular strain;Severities;Severity of illness;Site;skills;Specificity;study population;Symptoms;Techniques;Testing;Therapeutic;Therapeutic Trials;Time;Training;United States;United States National Institutes of Health;Validation;vascular bed;Vascular remodeling

PROJECT_TITLE: Pulmonary Vascular Disease as a Contributor to Respiratory Morbidity in Chronic Obstructive Pulmonary Disease


ORG_CITY: COLUMBIA

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Project Narrative One of the leading causes of death and disability within the VA health care system is when the heart cannot properly fill and eject blood; heart failure. One common cause of heart failure is that associated with high blood pressure, even when the blood pressure is controlled by medicine. This project will identify how we can better predict and understand this form of heart failure and most importantly identify new strategies for treating and potentially reversing this disease process. These results will set the stage for an entirely new treatment approach for VA patients suffering from this form of heart failure.

PI_NAMEs: SPINALE, FRANCIS G (contact)

PROJECT_TERMS: Acceleration;Animal Model;Animals;Aorta;Attenuated;attenuation;Blood;Blood Pressure;Cancer Biology;Cause of Death;Cellular biology;Coupled;Critical Pathways;Development;disability;Disease;Disease Progression;Early Diagnosis;EFRAC;Equilibrium;Event;Excision;Exercise;exercise regimen;Extracellular Matrix;falls;Family suidae;Fibroblasts;Foundations;Functional disorder;Health Care Costs;Healthcare Systems;Heart;Heart failure;Homeostasis;Hypertension;Impairment;improved;indexing;Left;Left Ventricular Function;Matrix Metalloproteinase Inhibitor;Matrix Metalloproteinases;Measures;Medicine;MicroRNAs;miRNA expression profiling;Modeling;Molecular;Morbidity - disease rate;mortality;Myocardial;new therapeutic target;novel diagnostics;novel therapeutic intervention;novel therapeutics;Outcome;Pathway interactions;Patients;Phenotype;Physiologic intraventricular pressure;porcine model;Post-Transcriptional Regulation;preservation;pressure;prevent;Prevention;Process;programs;Protocols documentation;Refractory;Regulation;response;restoration;Risk;Specific qualifier value;Standardization;Stimulus;Syndrome;synergism;Tissue Inhibitor of Metalloproteinases;tool;treadmill;Ventricular;Veterans

PROJECT_TITLE: Myocardial Plasticity in Heart Failure with Preserved Ejection Fraction (HFpEF)


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

ORG_CITY: CAPE TOWN

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: DESMOND TUTU HIV FOUNDATION

PHR: PROJECT NARRATIVE The global focus on women and key populations has curbed HIV related adverse outcomes for these groups, but men in high disease burden locations continue to remain at high risk of HIV acquisition and onward transmission. Pre-exposure prophylaxis (PrEP) research and interventions have prioritized women and key populations, with notable reductions in HIV acquisition in PrEP users. This study addresses a key gap in HIV prevention for men by assessing 1) factors associated with PrEP uptake, 2) factors associated with sustained PrEP use and attrition, 3) and using behavioral economics to design and prototype an HIV prevention intervention for South African males 15-49 years old in high disease burden communities.

PI_NAMEs: SMITH, PHILIP JOHN (contact)

PROGRAM_OFFICER_NAME: BANSAL, GEETHA PARTHASARATHY

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Adolescent and Young Adult;adverse outcome;Age;age group;aged;AIDS prevention;Alcohol consumption;antiretroviral therapy;Award;Behavioral;behavioral economics;Behavioral Sciences;Blood;burden of illness;care delivery;Caring;Cause of Death;Cessation of life;Child Care;Clinic;Clinical Management;Clinical Trials;cohort;Communities;community burden;Commuting;contextual factors;Data;design;Diphosphates;Dryness;Education;Educational workshop;Enrollment;Epidemiology;evidence base;Evidence based intervention;experience;Female;Foundations;Gender;girls;Goals;Grant;Health;Health behavior;health care service;health seeking behavior;Health Services;Healthcare;Heterosexuals;high risk;high risk men;HIV;HIV Infections;Human immunodeficiency virus test;human old age (65+);implementation science;Improve Access;improved;Individual;Inequity;innovation;insight;Intervention;Interview;Location;low and middle-income countries;male;male health;Measures;men;Mentors;Mentorship;Methods;Modeling;mortality;multidisciplinary;Outcome;Patients;Pattern;Population;pre-exposure prophylaxis;preference;premature;Prevalence;prevention service;preventive intervention;prototype;Province;Public Health;Qualitative Methods;Qualitative Research;Recommendation;Reporting;Research;Research Design;Research Methodology;Research Personnel;Resource-limited setting;response;Science;Scientist;Services;Sexual Health;sexual health intervention;Sexual Partners;social stigma;Socioeconomic Status;South Africa;South African;Spottings;Surveys;Tenofovir;theories;therapy design;Training;transmission process;treatment as prevention;Treatment outcome;United States National Institutes of Health;uptake;Viral;Visit;Wait Time;Woman;women versus men;Women's mortality;young man

PROJECT_TITLE: Male Access to Sexual Health Services and PrEP

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-ICP-L(57)R]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Biotechnology;Genetics;Neurosciences

ORG_CITY: NEW YORK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative The ability to smell is necessary for long-term physical and behavioral health in humans. Epidemiological studies suggest that older adults with impaired olfactory perception have a 4-fold increase in mortality within 5 years, and an increasing number of studies detect significant correlation between olfactory deficits and the future onset of neurodegenerative disorders, including Alzheimer’s. The proposed research is motivated not only by the desire to solve a fascinating molecular mystery that constitutes the keystone of olfaction, but also by the need to obtain insight to a sensory modality critical for human health.

PI_NAMEs: PULUPA, JOAN M. (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: Adaptor Signaling Protein;Advisory Committees;Alleles;Alzheimer's Disease;Architecture;Axon;behavioral health;Binding;Binding Sites;Cell Nucleus;Chemicals;Detection;Development;Disease;Distant;DNA;DNA Binding;DNA receptor;Down-Regulation;Enhancers;epidemiology study;experimental study;fascinate;Future;Gene Activation;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Genome;Goals;Health;Heterochromatin;Human;Image;Imaging Techniques;Individual;insight;Institution;Label;Laboratory Research;Lead;live cell imaging;Location;Maintenance;Measurement;Measures;Mediating;Messenger RNA;Microscopy;Modality;Modeling;Molecular;molecular imaging;mortality;mutant;Mutate;Mutation;Nature;Neurodegenerative Disorders;Neurons;Nuclear;Nucleoproteins;older adult;Olfactory dysfunction;Olfactory Pathways;olfactory receptor;olfactory sensory neurons;Optics;particle;Phase;physical conditioning;Positioning Attribute;postmitotic;Process;programs;protein protein interaction;Proteins;receptive field;receptor;receptor expression;Receptor Gene;recruit;Repression;Research;Sensory;Smell Perception;Spatial Distribution;Specificity;stoichiometry;System;Technology;temporal measurement;Time;Training;transcription factor;Transcriptional Regulation;Universities;Volatilization

PROJECT_TITLE: Identifying the mechanism of olfactory receptor gene regulation in olfactory neurons with live-cell imaging


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Genetics;Kidney Disease

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Surgically created arteriovenous fistulas (AVF) are the preferred approach to create a vascular access for hemodialysis in chronic kidney disease patients. However, AVFs fail at a high rate, thus imposing a huge burden on both the healthcare system and patients. This proposal investigates the cellular and molecular basis for AVF failure thereby providing knowledge that can be used to design future, rationally targeted therapies to enhance the success rate of this life-saving procedure.

PI_NAMEs: DARDIK, ALAN ;LONG, XIAOCHUN  (contact);SINGER, HAROLD A

PROGRAM_OFFICER_NAME: ABBOTT, KEVIN C

PROJECT_TERMS: activating transcription factor 3;Acute;Arteries;Arteriovenous fistula;ATAC-seq;Biochemical;Biological Assay;Blood Pressure;Blood Vessels;Cell Lineage;Cell Nucleus;Cell Proliferation;Cell Reprogramming;cell type;Cells;Chronic Kidney Failure;Clinical;clinically relevant;Clonal Expansion;Complement Factor B;Complex;Data;design;Extracellular Matrix;factor A;Failure;Fistula;Future;Gel;Genes;Growth Factor;Healthcare Systems;Hemodialysis;hemodynamics;Human;Hyperplasia;Impairment;improved;In Situ Hybridization;inhibitor;insight;Knockout Mice;Knowledge;Legal patent;Life;Ligation;MMP2 gene;Modification;Molecular;mouse model;Mus;myocardin;Nephrectomy;Nodal;novel;Nuclear;Operative Surgical Procedures;Pathway interactions;Patients;Periodicity;Phenocopy;Phenotype;Pluronics;pressure;Procedures;Process;programs;Property;Protein Isoforms;Regulation;Reporter;response;Role;Sampling;Sampling Studies;shear stress;Signal Transduction;Smooth Muscle Myocytes;Specimen;Stenosis;Stress;Stretching;success;targeted treatment;Testing;therapeutic target;Thick;Time;Transactivation;transcription factor;transcriptome sequencing;transcriptomics;Transducers;Vascular remodeling;Vascular Smooth Muscle;Veins;Venous;XCL1 gene

PROJECT_TITLE: Molecular control of vascular smooth muscle reprogramming in arteriovenous fistula maturation

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]


ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

ORG_STATE: MA

PHR: PROJECT NARRATIVE Type 1 diabetes is characterized by dysfunction and death of insulin-producing beta cells. We propose to develop general methods and reagents for targeted in vivo release of bioactive molecules in beta cells, and to discover new ligands against key beta-cell markers using the principles and techniques of chemical biology.

PI_NAMEs: CHOUDHARY, AMIT  (contact);KULKARNI, ROHIT N.

PROGRAM_OFFICER_NAME: GUPTA, DHANANJAY

PROJECT_TERMS: Adipose tissue;Beta Cell;Binding;Biology;Cadaver;Cell Proliferation;Cell Transplantation;cell type;Cells;Cessation of life;chemical reaction;Chemicals;Chemistry;Dependence;Development;Disease;efficacy evaluation;efficacy testing;fluorophore;Functional disorder;Graft Rejection;Human;Immune system;improved;In Vitro;in vivo;in vivo evaluation;Insulin;Insulin-Dependent Diabetes Mellitus;Ions;islet;Islets of Langerhans;Islets of Langerhans Transplantation;Kidney;Libraries;Ligand Binding;Ligands;Link;Liver;Mechlorethamine;Methods;Mitogens;Modality;Muscle;Nature;Oranges;Organism;Patients;Pharmaceutical Preparations;pharmacologic;Plasma;Procedures;Prodrugs;Proliferating;Reaction;Reagent;Replacement Therapy;Skeletal Muscle;small molecule;Sorting;Specificity;stem cell proliferation;System;Techniques;Testing;Therapeutic;therapeutic development;therapeutic target;Time;Zinc

PROJECT_TITLE: Development of platforms for beta cell-specific delivery and ligand discovery


NIH_SPENDING_CATS: Diabetes;Regenerative Medicine;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: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE The study and treatment of diabetes would greatly benefit from increased understanding of how human islets are formed. Improvements in this understanding will lead to the generation of these tissues from human stem cells for use in diabetes cell replacement therapy and drug screening.

PI_NAMEs: MILLMAN, JEFFREY ROBERT (contact)

PROGRAM_OFFICER_NAME: HWA, ALBERT J

PROJECT_TERMS: Actins;Affect;Attention;Behavior;Beta Cell;Blood Glucose;blood glucose regulation;C-Peptide;Cadaver;cell fate specification;Cell Physiology;cell replacement therapy;Cell Therapy;cell type;Cells;Cellularity;Chromatin;Cytoskeleton;Data;Development;Diabetes Mellitus;Diabetic mouse;diabetic patient;differentiation protocol;disease model;disorder control;Drug Screening;effective therapy;Endoderm;Enterochromaffin-like Cells;Event;Flow Cytometry;functional improvement;Gastrocoele;Gene Expression;Gene Expression Profile;Generations;Glucose;Goals;Hemorrhage;Human;human pluripotent stem cell;human stem cells;human tissue;Hypoglycemia;Implant;improved;In Vitro;in vivo;Individual;innovation;insight;Insulin;insulin secretion;Insulin-Dependent Diabetes Mellitus;islet;Islet Cell;Islets of Langerhans;Measures;method development;Molecular;Monitor;Outcome;Pancreas;Pathway interactions;Patients;Pattern;Performance;pluripotent stem cell differentiation;progenitor;Publishing;Regenerative Medicine;replacement tissue;Reporting;Research;response;restoration;Risk;Role;Safety;Serum;Signal Transduction;single cell sequencing;Source;Specific qualifier value;stem cell population;stem cells;success;Time;Tissues;Translations;Transplantation;Tube

PROJECT_TITLE: Studying the Role of the Microenvironment on Differentiation and Maturation of Beta Cells

STUDY_SECTION: BMDM

STUDY_SECTION_NAME: Basic Mechanisms of Diabetes and Metabolism Study Section[BMDM]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cancer;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Depression;Lung;Lung Cancer;Mental Health;Palliative Care;Patient Safety;Prevention;Rural Health

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative Caregiver Oncology Needs Evaluation Tool (CONNECT) empowers and educates caregivers about the benefits of supportive care services and systematically identifies unmet needs to connect lung cancer caregivers with a tailored list of supportive care resources. The intervention offers a scalable approach to reach a large number of lung caregivers, including vulnerable caregivers with barriers to in-person participation. Use of the NCI Community Oncology Research Program (NCORP) to plan for and pilot test this intervention will support future trial efficiency and yield findings generalizable to diverse caregivers, patients, and community oncology settings.

PI_NAMEs: NIGHTINGALE, CHANDYLEN LENAE (contact)

PROGRAM_OFFICER_NAME: CASTRO, KATHLEEN M

PROJECT_TERMS: Academic Medical Centers;acceptability and feasibility;Address;Anxiety;arm;base;cancer therapy;care delivery;care recipients;care systems;Caregiver Burden;caregiver interventions;Caregiver research;Caregivers;Caring;Clinic;clinically significant;Collaborations;Communication;Communities;Community Clinical Oncology Program;community setting;comparison group;Control Groups;Data;Data Collection;Databases;design;efficacy evaluation;efficacy testing;efficacy trial;empowerment;Enrollment;Ensure;Equity;ethnic minority;Evaluation;evidence base;experience;Family;Frequencies;Future;Goals;group intervention;health care service utilization;Human Resources;improved;improved outcome;informal support;innovation;interest;Intervention;intervention delivery;Investigation;Link;Lung;Malignant neoplasm of lung;Malignant Neoplasms;Medical;Mental Depression;Methods;minority patient;Modality;novel;Oncology;outpatient programs;Outpatients;Patients;Persons;Phase;phase III trial;pilot test;pilot trial;preference;primary outcome;Process;programs;Protocols documentation;Psychosocial Assessment and Care;Quality of Care;racial minority;Randomized;randomized, clinical trials;recruit;Reporting;Research;Research Design;Resources;Rural;secondary outcome;Self Care;Services;Site;standard care;success;Supportive care;Surveys;Testing;Time;tool;Training;Translating;trial enrollment;trial planning;Update;web-based intervention;willingness

PROJECT_TITLE: Multi-site Community Oncology Planning for the CONNECT Intervention Targeting Lung Cancer Caregivers


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_DEPT: PHYSIOLOGY

PHR: The initiation of DNA replication is central to cell proliferation and survival. Initiation pathways should be  susceptible to therapeutic intervention against bacterial infections and cancers; however, limitations in our  understanding of basic initiation mechanisms impede this goal. The proposed work will provide key  molecular models for understanding initiation proteins and activities and will establish new assays and  approaches for accelerating antibacterial discovery through efforts that target these factors.

PI_NAMEs: BERGER, JAMES M. (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Acceleration;Address;Affect;Anti-Bacterial Agents;ATP phosphohydrolase;Attention;Award;Bacteria;Bacterial Infections;Binding;Biochemical;Biochemistry;Biological Assay;Bypass;Cell Proliferation;Cell Survival;Closure by clamp;Collaborations;Complex;Curiosities;Data;Dependence;Disparate;DNA;DNA biosynthesis;DNA Damage;DNA Primase;DNA replication fork;DNA-Directed RNA Polymerase;drug discovery;ds-DNA;Enzymes;Gene Dosage;Genetic;Goals;Guanine Nucleotide Exchange Factors;helicase;Hydrolysis;In Vitro;in vivo;innovation;insight;Kinetics;Malignant Neoplasms;Methods;Modeling;Molecular;Molecular Conformation;Molecular Machines;molecular modeling;mutant;Nucleic Acids;operation;Outcome;Pathway interactions;Peptide Initiation Factors;Predisposition;Process;Prokaryotic Cells;Proteins;Reagent;Regulation;Replication Initiation;Research;rho;RNA;Severities;single molecule;small molecule;structural biology;System;tau Proteins;Testing;Therapeutic Intervention;translocase;Work

PROJECT_TITLE: Mechanistic Studies of Replication Initiation in Prokaryotes

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Pediatric;Rare Diseases;Women's Health Research

ORG_CITY: KANSAS CITY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE We have identified the first protective maternal genetic effect in palatogenesis. The proposed studies will determine whether the protective effect is due to changes in the maternal uterine environment and identify the underlying epigenetic or proteomic differences. Our long-term goal is to build upon these findings and identify therapeutic strategies to monitor or even improve the maternal environment to reduce the incidence of birth defects.

PI_NAMEs: SAADI, IRFAN  (contact);TRAN, PAMELA VIVIAN

PROGRAM_OFFICER_NAME: SAIFUDEEN, ZUBAIDA

PROJECT_TERMS: Actins;Affect;Alleles;autosome;Birth;calponin;Cells;Cilia;cilium biogenesis;Circulation;Cleavage Under Targets and Release Using Nuclease;cleft lip and palate;Cleft Palate;Coiled-Coil Domain;Complex;Congenital Abnormality;Congenital omphalocele;Craniofacial Abnormalities;Cytoskeletal Proteins;Cytoskeleton;Data;Disease;Embryo;embryo tissue;Embryo Transfer;Environment;Environmental Risk Factor;Epigenetic Process;Erinaceidae;Etiology;Exencephaly;experimental study;Fathers;Female;fetal;Folic Acid;Future;gain of function;Generations;Genes;Genetic;Genotype;GLI gene;Goals;Heterozygote;histone methylation;Human;improved;Incidence;insight;Intake;interest;male;Mediating;Methods;Microtubules;Modeling;Molecular;Monitor;Mothers;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;Nature;next generation sequencing;novel;Orbital separation excessive;orofacial cleft;Outcome;palatal shelves;palatogenesis;Parents;Phenotype;Placenta;promoter;protective effect;Proteomics;retrograde transport;Role;Signal Pathway;Signal Transduction;Smoking;Syndrome;Testing;Therapeutic;Tissues;transcriptome sequencing;Uterus

PROJECT_TITLE: Investigating the protective effect of maternal Thm1 heterozygosity against cleft palate

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: PROJECT NARRATIVE (RELEVANCE) Cell invasion through basement membrane barriers is crucial for tissue formation during development and immune cell trafficking to reach sites of infection. Cell invasion is also inappropriately co-opted in many human diseases including immune disorders and cancer. The proposed work will reveal how invasive cells acquire and use energy, build invasive structures, and withstand the stress of breaching basement membranes, which will advance our understanding of the mechanisms underlying cell invasion and generate new therapeutic strategies to modulate this behavior in developmental disorders and other human diseases.

PI_NAMEs: SHERWOOD, DAVID R (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Adhesions;Arthritis;Asthma;Basement membrane;Behavior;Biological Process;Caenorhabditis elegans;Cell membrane;Cell model;Cell Physiology;cell type;Cells;Clinical Trials;Communication;Development;developmental disease;Disease;Disseminated Malignant Neoplasm;Electron Transport;Enzymes;Event;experimental study;Extracellular Matrix;functional genomics;Genetic;genetic manipulation;Genetic Transcription;genome editing;Genomic approach;Glucose;healing;Health;Human;human disease;Immune;Immune System Diseases;improved;in vitro Assay;in vivo;in vivo Model;Infection;Injury;Invaded;lipid biosynthesis;Lipids;Malignant Neoplasms;Matrix Metalloproteinase Inhibitor;Matrix Metalloproteinases;Membrane;migration;Mission;Mitochondria;Molecular;Multiple Sclerosis;novel therapeutic intervention;overexpression;prevent;programs;sensor;Site;Stereotyping;Stress;Stroke;Structure;Therapeutic;Tissues;trafficking;Transcriptional Regulation;United States National Institutes of Health;Visual;Visualization;Work

PROJECT_TITLE: Understanding how cells invade through basement membrane in vivo

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


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Digestive Diseases;Genetics;Inflammatory Bowel Disease;Microbiome

ORG_NAME: OKLAHOMA MEDICAL RESEARCH FOUNDATION

PHR: PROJECT NARRATIVE  Approximately 15% of patients with ulcerative colitis (UC) develop medically refractory disease or colorectal neoplasia requiring special surgery called IPAA to remove the diseased large intestine and to restore partial bowel function. An inflammatory disease, termed pouchitis, is a common and inadequately treated complication of IPAA. The proposed project is poised to provide novel insights into the role of intestinal mucin-type O-glycans in intestinal mucus barrier function and in pathogenesis of the common human disease, which may lead to a novel therapy for patients with UC.

PI_NAMEs: CASERO, DAVID ;XIA, LIJUN  (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Address;Adopted;Affect;analytical method;Anastomosis - action;Anus;Biological;Biological Process;Biopsy;Cells;Chromatin;cohort;Colon;Colorectal Neoplasms;commensal bacteria;Communities;Complication;Data;Disease;disease phenotype;Distal;Encapsulated;Epithelium;Excision;Exhibits;Feces;Gel;Genes;Genetic;genetic variant;Genetic Variation;Genomics;glycosylation;Goblet Cells;gut homeostasis;Heterogeneity;Homeostasis;Human;human disease;Ileal Reservoirs;Immune;Impairment;Inflammation;Inflammatory;Inflammatory Bowel Diseases;insight;intestinal barrier;Intestines;Large Intestine;Lectin;Link;Maintenance;Medical;Methods;microbiome;microbiome alteration;microbiota;Modeling;Molecular;Mucin-2 Staining Method;Mucins;Mucous body substance;Mucous Membrane;Mucus-Secreting Cell;Mus;Names;novel;novel diagnostics;novel therapeutics;Operative Surgical Procedures;Paper;Pathogenesis;Patients;Phenotype;Physiological;Polysaccharides;Population;Pouchitis;Production;Publications;Publishing;quantitative imaging;Refractory Disease;Research;Risk;RNA;Role;Science;segregation;single-cell RNA sequencing;Spontaneous colitis;Stains;Surface;Surgical Models;Symbiosis;System;Testing;Thick;Tissues;transcriptomics;Ulcerative Colitis

PROJECT_TITLE: Colon O-glycosylated mucus in the homeostasis of microbiota and host

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


NIH_SPENDING_CATS: Genetics;Immunotherapy;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project Narrative Legionella are facultative, intracellular bacteria residing in aquatic environments from which contaminated inhaled aerosols cause accidental infections leading to an increasing incidence of Legionnaires’ disease in the United States. Here, we hypothesize a critical role of the immune-modulatory cytokine, IL-27, signaling via its IL-27RA receptor for the immune pathogenesis of Legionellosis. The proposed studies aim for new insights into the molecular pathways of IL-27 production in infected macrophages and the lymphocyte-type specific activities of IL27RA to establish a solid knowledge basis for targeted therapies in future.

PI_NAMEs: BOSMANN, MARKUS  (contact)

PROJECT_TERMS: Ablation;Accidents;Acute;Acute Respiratory Distress Syndrome;Adoptive Cell Transfers;Aerosols;Alveolar Macrophages;Amoeba genus;Antibodies;atypical pneumonia;Bacteria;Binding;Body Weight decreased;Bronchoalveolar Lavage;Bronchoalveolar Lavage Fluid;Cell Communication;Cell Maturation;cell type;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Cessation of life;Chimera organism;Chimeric Proteins;Chronic;Clinical;cytokine;Cytoprotection;Data;Death Rate;Defect;Dendritic Cells;Dimensions;Disease;Engineering;Environment;experimental study;Family;Future;Gene Deletion;Genetic Transcription;Habitats;high risk;Histology;Human;IL27RA gene;Immune;Immune response;Immunologic Receptors;immunopathology;Immunosuppression;Impairment;improved;Incidence;Infection;Infiltration;Inflammation;Inflammatory Response;Inhalation;innate immune sensing;insight;Interferon Type II;Interleukin-12;Interleukin-6;Interleukins;Invaded;ITGAM gene;Knock-out;Knowledge;Legionella;Legionella longbeachae;Legionella pneumophila;Legionellaceae;Legionellosis;Legionnaires' Disease;Ligation;Lung;Lung infections;Lymphocyte;Macrophage;Mediating;Mediator;Molecular;monocyte;Mononuclear;mortality;multidimensional data;Mus;Myeloid Cells;Natural Killer Cells;Neutrophil Infiltration;NK Cell Activation;novel;organ injury;Outcome;Parasites;pathogen;Pathogenesis;Pathway interactions;Patients;Pattern recognition receptor;PD-1/PD-L1;Phagocytes;Phagocytosis;Phosphoproteins;Phosphorylation;Play;Pneumonia;Production;programs;protein biomarkers;receptor;Receptor Activation;Regulatory T-Lymphocyte;Reporter;Reporting;Research;Resistance;Respiratory physiology;Role;Sampling;Severities;Signal Pathway;Signal Transduction;Solid;Source;STAT1 gene;STAT3 gene;Surrogate Endpoint;T cell response;T-Cell Activation;T-Lymphocyte;targeted treatment;Testing;transcriptome;United States;Vacuole;Virulent;Wild Type Mouse;γδ T cells

PROJECT_TITLE: Interleukin-27 in host response to Legionella infection

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Clinical Research;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE Acute myeloid leukemia (AML) is a fatal blood cancer with heterogeneous underlying genetics that can be treated, albeit with variable success, using either intensive chemotherapy, for those patients able to tolerate it, or less intensive regimens in combination with oral agents that trigger cell death in leukemic cells. We have adopted a functional test capable of measuring the intrinsic potential for a particular AML cell to undergo cell death, which we hypothesize will predict treatment response to cell death-inducing agents and thus identify patients most likely to benefit from a specific treatment. The proposed research will also seek to distinguish mutations present in poor-risk TP53-mutant AML as bystander mutations or drivers of AML disease progression which mediate resistance to standard therapies.

PI_NAMEs: CAI, SHENG  (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adopted;Amalgam;Apoptotic;Attenuated;Azacitidine;Back;BCL2 gene;BH3 Domain;Bioinformatics;Biological;Biological Assay;Biological Markers;Biology;biomarker validation;Blood;burden of illness;career development;Categories;Cell Death;Cell Death Induction;Cells;Cessation of life;chemotherapy;Chromosomal Instability;Chromosome abnormality;Clinical;Clonal Evolution;Clonal Expansion;Combined Modality Therapy;Complex;Cytogenetics;Data;Dedications;Development Plans;differential expression;Disease;Disease Progression;Disease remission;Dissection;DNA Sequence Alteration;drug sensitivity;Engraftment;Enterobacteria phage P1 Cre recombinase;Epigenetic Process;Erythroid;Event;Exhibits;FDA approved;FLT3 gene;Genetic;Genetic Transcription;Genomic Instability;Genotype;Goals;Hematologic Neoplasms;Hematopoietic Neoplasms;Hematopoietic stem cells;high risk;Human;individualized medicine;Induction of Apoptosis;inhibitor;interest;Karyotype;Knowledge;leukemia;leukemia treatment;Leukemic Cell;leukemic transformation;loss of function;Maintenance;Malignant Neoplasms;Measures;Mediating;Megakaryocytes;Memorial Sloan-Kettering Cancer Center;Mentors;Mitochondria;Modeling;Molecular;mortality;mouse model;Mus;mutant;Mutation;novel;NPM1 gene;Oral;Outcome;Pathogenesis;Pathway interactions;patient derived xenograft model;Patients;Peptides;Pharmaceutical Preparations;Phase;precision oncology;predicting response;Prediction of Response to Therapy;predictive test;progenitor;prognostic;programs;Randomized;recombinase;Regimen;Relapse;relapse patients;Research;Research Personnel;Resistance;response;restoration;Risk;Role;Sampling;Secondary acute myeloid leukemia;standard of care;success;System;Tertiary Protein Structure;Testing;Therapeutic;therapeutic biomarker;therapeutic target;therapy resistant;Time;TP53 gene;TP53-mutant acute myeloid leukemia;Training;treatment planning;treatment response;Validation;Work;Xenograft procedure

PROJECT_TITLE: Investigating apoptotic priming as a determinant of sensitivity to leukemia-directed therapies

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Effects of Indoor Air Pollution;Infectious Diseases;Lung;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_CITY: COLLEGE PARK

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

PHR: PROJECT NARRATIVE Despite outbreaks of COVID-19 among Black and/or Latinx migrant and seasonal farmworkers (MSFWs), few studies have comprehensively evaluated these disparities through the lens of structural racism (SR) which is defined as the macro level systems, social forces, institutions, ideologies, and processes that interact with one another to generate and reinforce inequities among racial/ethnic groups. Our study will be the first to combine environmental health science, community-based system dynamics (CBSD) theory, statistical analysis and public health approaches with legal analysis to unpack the mechanisms through which SR shapes COVID-19 trends among Black and/or Latinx MSFWs. Our proposed study will inform the design of policies and best practices to counter long-standing mechanisms of SR impacting MSFWs, optimize living and working conditions for better health protections and to control future outbreaks of infectious disease among these invisible and vulnerable workers.

PI_NAMEs: PAYNE-STURGES, DEVON C (contact)

PROGRAM_OFFICER_NAME: O'FALLON, LIAM

PROJECT_TERMS: 2019-nCoV;Address;Advocate;Affect;Agricultural Workers;Agriculture;Automobile Driving;Black race;built environment;care outcomes;care seeking;Communicable Diseases;Communities;County;COVID-19;COVID-19 disparity;COVID-19 impact;COVID-19 outbreak;COVID-19 pandemic;Crowding;Crows;Decision Making;design;Detection;disorder risk;Disparity;dynamic system;Employment;Environment;Environmental Health;Equity;Ethnic Population;Exclusion;Exposure to;Farm;farm worker;Fright;future outbreak;future pandemic;Goals;Government;Hand;Health;health care availability;health care disparity;health inequalities;Health protection;Healthcare;Housing;Hygiene;Immigration;Indoor Air Quality;Industry;Inequity;innovation;Institution;interdisciplinary approach;Interruption;Latinx;Laws;Legal;lens;Linguistics;Longitudinal Studies;marginalization;Medical;Migrant;minority health;minority health disparity;Modeling;multidisciplinary;novel;Occupational Health;Outcome;Pathway interactions;Pattern;Pilot Projects;Policies;Policy Analysis;Policy Maker;Policy Making;Population;Population Surveillance;prevent;Preventive care;Preventive measure;Process;Public Health;public health intervention;Public Housing;Quasi-experiment;Race;racial health disparity;racial population;racism;Regulation;Reporting;Research;Research Design;Research Priority;Respiratory Disease;respiratory health;respiratory virus;response;Risk;Role;Safety;SARS-CoV-2 B.1.617.2;Seasons;segregation;Shapes;social;Social Distance;Social Policies;Statistical Data Interpretation;Structural Racism;Structure;System;Technical Expertise;Testing;theories;Time;trend;United States;United States National Institutes of Health;Virus;Vision;Vulnerable Populations;Water;Work

PROJECT_TITLE: Research Employing Environmental Systems and Occupational Health Policy Analyses to Interrupt the Impact of Structural Racism on Agricultural Workers and Their Respiratory Health (RESPIRAR)


PHR: PROJECT NARRATIVE In patients with non-small cell lung cancer, combination treatment with chemotherapy and T cell checkpoint inhibition is more efficacious than chemotherapy alone, so it has recently become the standard of care. Despite increasing enthusiasm for this combination treatment, the reasons for its combinatorial efficacy remain unclear. We seek to understand these reasons by investigating treatment-induced mediators of inflammation which, if identified, would allow for rationally designed combinations and inform further drug discovery efforts.

PI_NAMEs: BOTT, MATTHEW J (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Affect;anti-PD-L1;Autologous;Basic Science;Biological Assay;Cancer Biology;Cancer Etiology;cancer therapy;career;CDK4 gene;Cell Aging;Cell Cycle Arrest;Cell Death;Cell secretion;Cells;checkpoint inhibition;chemotherapy;Cisplatin;Clinical;Coculture Techniques;Combination Drug Therapy;combinatorial;Combined Modality Therapy;conventional therapy;cytokine;cytotoxicity;Data;Development;Drug Combinations;drug discovery;Educational Curriculum;efficacy evaluation;Environment;Faculty;Future;Gene Expression Profile;Genes;Goals;Growth;Human;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;Immuno-Chemotherapy;Immunocompetent;immunogenicity;Immunologic Stimulation;Immunologic Surveillance;Immunooncology;immunoregulation;Immunotherapy;improved outcome;In Vitro;in vitro Assay;in vivo;Induced Mutation;Infiltration;Inflammation Mediators;inhibitor;interest;International;Knowledge;knowledge base;Laboratories;lung cancer cell;Lung Neoplasms;Malignant neoplasm of lung;Mediating;Mediator;MEKs;member;Memorial Sloan-Kettering Cancer Center;Mentorship;Methods;Modeling;mortality;mouse model;Mutagens;Mutation Spectra;neoplastic cell;Non-Small-Cell Lung Carcinoma;novel;Organoids;Pathway interactions;Patient Care;patient population;Patient-Focused Outcomes;Patients;Phenotype;Phosphotransferases;Platinum;Population;Prediction of Response to Therapy;Production;randomized trial;randomized, clinical trials;rational design;Regimen;Research;Research Personnel;Resected;response;Role;Sampling;Scientific Inquiry;senescence;senescent cell;Signal Pathway;Specimen;standard of care;Stimulator of Interferon Genes;Structure;surgical service;System;T-Lymphocyte;targeted treatment;Technical Expertise;Testing;Thoracic Surgical Procedures;TP53 gene;transcriptomic profiling;Translational Research;transplant model;treatment response;tumor;Tumor Immunity;Tumor-Infiltrating Lymphocytes;Work

PROJECT_TITLE: Exploring the combinatorial efficacy between chemotherapy and T cell checkpoint inhibition and the role of cellular senescence


ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: NARRATIVE Diseases of the endocrine system constitute major public health problems in the US and worldwide. The objective of this Training Program is to prepare physician scientists to pursue research careers addressing mechanisms and treatment of human disease with focus on the endocrine system. Trainees from this Program will identify disease mechanisms, and develop and implement new effective treatments, whose applications will improve human health.

PI_NAMEs: BELL, GRAEME I;MIRMIRA, RAGHAVENDRA G (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Clinical;Endocrinology;Research

PROJECT_TITLE: Integrated Clinical and Basic Endocrinology Research


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Genetics;Human Genome

ORG_CITY: IOWA CITY

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE: Tooth loss is one of the most common organ failures. However, our current understanding of the initiation stages of tooth development is limited. The overall objective of this proposal is to dissect the molecular and cellular mechanisms of tooth initiation, particularly the core transcriptional regulatory networks that drive specification of dental lamina, versus other epithelial fates, within the maxillary and mandibular ectoderm. The long-term goal is to apply the mechanisms uncovered for regenerative therapeutic approaches.

PI_NAMEs: CAO, HUOJUN  (contact);VAN OTTERLOO, ERIC

PROGRAM_OFFICER_NAME: CHOU, ALICIA YESIU

PROJECT_TERMS: Adult;Aging;Animal Model;Biological Assay;catalyst;Cell Lineage;Cells;Cleavage Under Targets and Release Using Nuclease;Communication;Congenital Abnormality;Coupled;craniofacial;Defect;Dental;Development;Ectoderm;Ectoderm Cell;Ectopic Expression;Elderly;Environment;Epithelium;Experimental Designs;experimental study;Fibroblast Growth Factor;Future;Gene Expression;Genes;Genetic;Genetic Transcription;genome-wide;Goals;Health;Human;improved;in vivo;Incisor;Knock-out;Knockout Mice;Knowledge;Lasers;Lead;Life;Mandible;Maxilla;Mesenchyme;Microdissection;Modeling;Molecular;Morphology;mouse model;Mouth Diseases;multiple omics;Mus;Natural regeneration;Oral;oral cavity epithelium;Organ failure;Outcome Study;overexpression;permanent tooth;Population;Program Development;programs;regenerative therapy;repaired;Repression;Reptiles;Research;Shark;SHH gene;Side;Signal Pathway;single-cell RNA sequencing;Skin;spatiotemporal;Specific qualifier value;Specificity;stem cell based approach;Stem Cell Development;Structure;Supernumerary Tooth;Testing;Time;Tissue Recombination;Tooth Loss;Tooth regeneration;Tooth structure;transcription factor;transcription regulatory network;transcriptome;transcriptome sequencing;Trauma;Up-Regulation

PROJECT_TITLE: Identifying the core transcriptional regulatory network initiating a tooth program


NIH_SPENDING_CATS: Endocrine Disruptors;Health Effects of Indoor Air Pollution;Lung;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention

ORG_CITY: CINCINNATI

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: PUBLIC HEALTH RELEVANCE Replacement flame retardants are under consideration for regulation by the U.S. Environmental Protection Agency (EPA) under the Toxic Substances Control Act (TSCA). They are ubiquitous in the indoor environment which is a major determinant for respiratory conditions ranging from respiratory infections to asthma, the most common chronic disease in children. Therefore, it is of public health importance to determine the association of these chemicals with adverse respiratory outcomes in order to inform preventive measures aimed at reducing respiratory disease burden.

PI_NAMEs: MENDY, ANGELICO  (contact)

PROGRAM_OFFICER_NAME: QUINN, ASHLINN KO

PROJECT_TERMS: 1 year old;5 year old;Acetylcholinesterase;Adult;Age;Air;Alveolar;Area;Asthma;bead chip;Binding;Biological;Birth;Bronchoconstriction;burden of illness;case control;Cells;chemical association;Chemicals;Child;Childhood;Chronic Disease;cohort;consumer product;Deposition;design;Development;DNA Methylation;Dust;early childhood;Endocrine disruption;Environment;Environmental Exposure;Epigenetic Process;epigenome;Esters;exposure route;Exposure to;Flame Retardants;Genes;Goals;Hay fever;Health;high risk;House Dust;Household;Hypersensitivity;Impairment;in utero;Indoor environment;Inhalation;innovation;inorganic phosphate;Investigation;irritation;Knowledge;Measurement;Measures;Mediating;metropolitan;multi-ethnic;Muscarinic M2 Receptor;novel strategies;Ohio;Organophosphates;Outcome;Oxidative Stress;particle;Patient Self-Report;Phase;Placenta;Poison;polybrominated diphenyl ether;postnatal;Predisposition;Pregnancy;prenatal;prenatal exposure;Preventive measure;Production;Prospective Studies;Public Health;public health relevance;pulmonary function;Pulmonary Function Test/Forced Expiratory Volume 1;Pulmonary Inflammation;Pulmonary Surfactants;receptor function;Regulation;respiratory;Respiratory Disease;respiratory health;Respiratory Signs and Symptoms;Respiratory Tract Infections;response;Risk;skin irritation;Surface;Symptoms;Testing;Toxic effect;Umbilical Cord Blood;United States Environmental Protection Agency;urinary;Urine;vapor;Volatilization;Wheezing

PROJECT_TITLE: Childhood and In utero Exposure to Organophosphate and Replacement Brominated Flame Retardants and Child Respiratory Outcomes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-C(02)]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative: A common feature of heart failure is fatty acid (FA) oxidation inhibition and boosting FA oxidation is beneficial in animal models of heart failure; however, the mechanisms that suppress FA oxidation remain unclear. In this proposal, I uncover an unappreciated role for peroxisomes, an essential organelle for FA oxidation, in ischemic heart failure and define the mechanism by which ischemia promotes peroxisome loss. These studies provide important insight into metabolic remodeling in heart failure and will help develop a novel therapeutic strategy in this disease.

PI_NAMEs: WYANT, GREG  (contact)

PROGRAM_OFFICER_NAME: WONG, RENEE P

PROJECT_TERMS: Acute;Address;Advisory Committees;Animal Model;Autophagocytosis;Award;Binding Proteins;Biochemical;Cardiac Death;Cardiac Myocytes;career;Cell Death;Cessation of life;Chronic;Clinical;Consumption;Dana-Farber Cancer Institute;Data;Data Set;detection of nutrient;Development;Disease;Drug Targeting;Environment;Experimental Genetics;experimental study;fatty acid oxidation;Functional disorder;Genes;Genetic Screening;Glycolysis;Goals;Heart failure;heart function;Hip region structure;Hypoxia;Hypoxia Inducible Factor;improved;In Vitro;in vivo;insight;Ischemia;ischemic cardiomyopathy;Knowledge;Laboratories;Maintenance;Measures;Mediating;Mentors;Metabolic;Metabolism;metabolome;Mitochondria;mouse model;Myocardial dysfunction;Myocardial Ischemia;Natural History;novel;novel marker;novel therapeutic intervention;novel therapeutics;Organelles;Oxygen;Pathway interactions;peroxisome;Phase;Plasma;pre-clinical;Premature Mortality;prevent;Process;programs;Proteins;receptor;recruit;Reperfusion Injury;Repression;Research;Research Personnel;Research Training;response;Role;Severities;Stroke;Supplementation;symposium;tenure track;Testing;Therapeutic;Tissues;Training;transcription factor

PROJECT_TITLE: Mechanistic Understanding of Hypoxia-Induced Peroxisome loss: Implications for Heart Failure


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

NIH_SPENDING_CATS: Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research

PI_NAMEs: KESHAVARZIAN, ALI ;KUPFER, SONIA  (contact)

PROGRAM_OFFICER_NAME: BOUGH, KRISTOPHER J

PROJECT_TERMS: Appointment;biomedical informatics;career;Chicago;Clinical Research;Collaborations;Faculty;faculty mentor;Funding;Goals;graduate school;Health;health equity;Informatics;informatics training;K-Series Research Career Programs;medical schools;member;Mentors;Minority Groups;National Research Service Awards;next generation;Occupations;peer learning;post-doctoral training;Postdoctoral Fellow;pre-doctoral;programs;Public Health;Research;Research Personnel;Research Training;skills;Structure;Time;TNFSF15 gene;Training;training opportunity;Training Programs;Translational Research;translational scientist;Underrepresented Minority;Universities

PROJECT_TITLE: J. NRSA Training Core


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Human Genome;Immunotherapy;Networking and Information Technology R&D (NITRD);Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Project Narrative This study efficiently utilizes existing resources to comprehensively assess factors ranging from biology to lifestyle to treatment and neighborhood context and their contributions to the survival advantage observed among Asian American women. Elucidation of factors that contribute to the survival advantage among Asian American breast cancer patients have the potential to inform the improvement of survival in all groups of women.

PI_NAMEs: AMBROSONE, CHRISTINE B.;GOMEZ, SCARLETT L (contact);KUSHI, LAWRENCE H

PROGRAM_OFFICER_NAME: GALLICCHIO, LISA M

PROJECT_TERMS: Accounting;Adherence;Algorithms;American;anti-tumor immune response;Asian Americans;Asian population;Automobile Driving;Behavior;Biological;Biology;black women;Body Size;breast cancer diagnosis;breast cancer family registry;Breast Cancer Patient;breast cancer survival;California;Cancer Biology;cancer health disparity;cancer immunobiology;cancer immunotherapy;Cancer Prognosis;cancer survival;Cells;Characteristics;chemotherapy;Chinese;Clinical;cohort;Cohort Studies;comparison group;Complementary and alternative medicine;contextual factors;Data;data integration;data registry;Dietary intake;disorder risk;Disparity;Electronic Health Record;Epidemiology;ethnic difference;ethnic disparity;Ethnic Origin;Ethnic Population;experience;follow-up;Genetic;Health behavior;health care availability;Health Promotion;Healthcare Systems;Heterogeneity;hormone therapy;Immigration;Immune;immune cell infiltrate;Immune response;Immunobiology;Immunogenomics;Immunologic Receptors;improved;Individual;insight;Japanese;Knowledge;Latina;Life Style;lifestyle factors;Maintenance;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Modeling;mortality;multi-ethnic;Neighborhoods;neoplasm registry;Outcome;Pathway interactions;Patient Self-Report;Patients;Pattern;Phenotype;Plants;Population;Population Group;Population Heterogeneity;Prevalence;prognostic;prognostic assays;Prognostic Factor;prognostic indicator;protective factors;Race;racial difference;racial disparity;racial population;Research;Resources;Sampling;Site;Social Environment;Social Network;Social support;sociocultural determinant;Socioeconomic Status;Survival Rate;The Cancer Genome Atlas;Time;tissue archive;Tissue Sample;Tissues;transcriptome sequencing;Translating;treatment adherence;Treatment Factor;Treatment outcome;tumor;tumor microenvironment;Tumor Tissue;United States;White Women;Woman;Women's Group

PROJECT_TITLE: Insights from Asian Populations into Disparities in Breast Cancer Prognosis and Outcomes

STUDY_SECTION: CHSA

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


NIH_SPENDING_CATS: Clinical Research

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PI_NAMEs: WIDLANSKY, MICHAEL E (contact)

PROGRAM_OFFICER_NAME: DIBELLO, ANTHONY THOMAS

PROJECT_TERMS: Acceleration;Award;Basic Science;career;career development;Clinical;clinical care;Clinical Research;Clinical Sciences;clinical translation;Department chair;design;Development Plans;Discipline;Education;Ensure;Environment;experience;Funding;Goals;Grant;improved;Institution;Interdisciplinary Study;Leadership;Learning;Link;Manuscripts;Measures;Medicine;member;Mentors;mid-career faculty;minority investigator;multidisciplinary;Physician Executives;population health;Productivity;Program Evaluation;programs;Publishing;Qualifying;recruit;Research;research and development;Research Personnel;Research Training;Role;Science;senior faculty;skills;Time;Training;Training Programs;Translational Research;translational scientist;Translations;Underrepresented Minority;United States National Institutes of Health

PROJECT_TITLE: Institutional Career Development Core


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Genetics;Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative Trypanosomatid parasites infect 18-20 million people world-wide and are responsible for devastating diseases, yet drug therapies remain inadequate. Polyamine biosynthesis is a proven drug target for the treatment of Human African Trypanosomiasis (HAT), and the finding of both novel polyamine metabolites and regulatory mechanisms suggest that additional therapeutic targets may be found that could be effective against all three pathogenic trypanosomatids. We propose to continue our long-standing efforts to understand the metabolism and regulation of this pathway using the causative agent of HAT, Trypanosoma brucei, as a model to uncover novel trypanosomatid biology that might be exploited for drug discovery.

PI_NAMEs: PHILLIPS, MARGARET A. (contact)

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Adenosylmethionine Decarboxylase;African Trypanosomiasis;Agmatine;Anabolism;Antibodies;Binding;Binding Sites;Biochemical;Biochemistry;Biological;Biological Assay;Biological Process;Biology;biophysical techniques;Candidate Disease Gene;candidate identification;Cations;Cattle;cell growth;Cells;cellular engineering;Cellular Metabolic Process;Chagas Disease;cofactor;Complex;crosslink;Crystallography;Decarboxylation;deoxyhypusine;deoxyhypusine monooxygenase;deoxyhypusine synthase;Disease;disorder risk;drug discovery;Economic Development;economic impact;Eflornithine;eIF-5A;Elongation Factor;Enzymes;Equilibrium;Eukaryota;Eukaryotic Cell;Foundations;Genetic;genetic approach;Genomic approach;Glutathione;Goals;Grant;Growth;Human;Hydroxylation;hypusine;inhibitor;interest;Isotope Labeling;Knock-out;Label;Leishmania;Leishmaniasis;Link;Maintenance;Mammalian Cell;Messenger RNA;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Modeling;Modification;Molecular;Mutagenesis;nagana;Names;neglected tropical diseases;novel;Null Lymphocytes;Nutritional Requirements;Ornithine;Ornithine Decarboxylase;Oxidation-Reduction;Parasites;Parasitic Diseases;Pathogenicity;Pathway interactions;Persons;pharmacologic;Pharmacotherapy;Play;Polyamines;polycation;Populations at Risk;programs;protein expression;Proteins;Proteomics;Putrescine;Reaction;Regulation;response;Role;Running;S-Adenosylhomocysteine;S-Adenosylmethionine;sensor;Signal Transduction;Site;Spermidine;Spermidine Synthase;Structure;Sulfhydryl Compounds;targeted treatment;therapeutic target;tool;Translating;translation factor;Translations;Trypanosoma;Trypanosoma brucei brucei;Trypanosoma cruzi;trypanothione;uptake;Wasting Syndrome;Work;X-Ray Crystallography

PROJECT_TITLE: POLYAMINE AND TRYPANOTHIONE METABOLISM IN TRYPANOSOMA BRUCEI

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


PHR: PROJECT NARRATIVE Autophagy, literally meaning self-eating, is a cell renewal process that is implicated in many human diseases. Autophagy is recognized to recycle cellular components in the cytoplasm, but my study suggests that it also recycles constituents from the nucleus. I aim to study this new perspective of autophagy, and hypothesize that this nuclear role of autophagy helps cells to resolve adverse conditions.

PI_NAMEs: DOU, ZHIXUN  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TITLE: Autophagy degradation of nuclear and chromatin constituents

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


NIH_SPENDING_CATS: Brain Disorders;Drug Abuse (NIDA only);Genetics;HIV/AIDS;Infectious Diseases;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: PHILADELPHIA

ORG_DEPT: NEUROSCIENCES

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: NARRATIVE Our proposed study will obtain empirical evidence to demonstrate synergistic involvement of HIV-1 and morphine in altered pre-mRNA splicing of OPRM1 (the -opioid receptor) leading to preferential expression of MOR-1X isoform with implications for enhanced opioid dependence observed in people with HIV (PWH). In addition, it will provide essential understanding of the mechanisms underlying alternative splicing of OPRM1 and unique cellular pathways associated with MOR-1X -mediated intracellular signaling. Our proposed studies will also develop strategies to reverse morphine and HIV-1 -induced missplicing of OPRM1.

PI_NAMEs: CHANG, SULIE L.;SARIYER, ILKER KUDRET (contact)

PROGRAM_OFFICER_NAME: BORGMANN, KATHLEEN RUTH

PROJECT_TERMS: Alternative Splicing;Antisense Oligonucleotides;Autopsy;Behavior;Binding;Biochemical;Brain;Brain region;brain tissue;C-terminal;Cell Culture Techniques;Cells;Chronic;Clinical;Consensus;Cyclic AMP;Data;Development;Drug abuse;Elements;Event;Exons;exosome;Exposure to;extracellular vesicles;Family;Functional disorder;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Gene Activation;genetic regulatory protein;Heroin;HIV;HIV Envelope Protein gp120;HIV Infections;HIV-1;HIV/AIDS;Human;Illicit Drugs;In Vitro;in vivo;Inbred F344 Rats;Incidence;Individual;Mediating;member;Messenger RNA;Modeling;Molecular;Morphine;Morphine Dependence;mRNA Precursor;Muscarinic M1 Receptor;N-terminal;nef Protein;Neurocognitive;Neuroglia;Neurons;novel;Opiate Addiction;opioid abuse;Opioid Receptor;opioid use;Oral;Pathologic;Pathway interactions;Peripheral Blood Mononuclear Cell;Persons;Phosphotransferases;Physical assessment;Physical Dependence;Physiological;Protein Isoforms;Protein Kinase;Rattus;Recombinants;Regulation;Reporting;Research;response;Rewards;RNA;RNA Splicing;Role;secretory protein;Self Administration;Signal Pathway;Signal Transduction;Spinal Cord;Tail;Tissues;Transcript;Viral;Withdrawal

PROJECT_TITLE: Modulation of OPRM1 alternative splicing by morphine and HIV-1 Nef

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]