NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Emerging Infectious Diseases;Immunization;Infectious Diseases;Orphan Drug;Prevention;Rare Diseases;Vaccine Related

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

PHR: PROJECT NARRATIVE Kaposi sarcoma-associated herpesvirus is the causal agent of Kaposi sarcoma, a cancer that is very common in immunocompromised people (such as HIV/AIDS and transplant patients). We have designed a vaccine based on virus-like particles, with a goal to elicit antibody-mediated immune responses in three pre-clinical animal models (wild-type mice, humanized mice, and common marmoset monkeys). We expect to generate data that support future testing of our vaccine in humans as a candidate to prevent Kaposi sarcoma-associated herpesvirus infection and its associated cancers.

PI_NAMEs: OGEMBO, JAVIER GORDON (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Adult;Animal Model;Animals;Antibodies;Antibody Response;Antibody titer measurement;B-Cell Lymphomas;B-Lymphocytes;Callithrix;Callithrix jacchus jacchus;cancer prevention;Carcinogens;CD34 gene;cell type;Cells;Child;Classification;Data;design;Developed Countries;Developing Countries;Development;Disease;Dose;early childhood;efficacy evaluation;Endothelium;Enzyme-Linked Immunosorbent Assay;Epithelium;Fibroblasts;FK506;Funding;Future;Glycoproteins;Goals;Herpesviridae;Herpesviridae Infections;Herpesvirus Vaccines;HIV/AIDS;Human;Human Herpesvirus 8;humanized mouse;Iatrogenesis;Immune;Immune response;Immunization;Immunize;Immunocompetent;Immunocompromised Host;immunogenic;immunogenicity;Immunoglobulin G;immunological status;immunosuppressed;Immunosuppression;In Vitro;in vivo;Incidence;Individual;Infection;innovation;International Agency for Research on Cancer;Kaposi Sarcoma;Licensing;Malignant Neoplasms;Marketing;Measures;Mediating;Membrane Glycoproteins;Modeling;Modified Vaccinia Virus Ankara;Monkeys;Mus;Myeloid Cells;neutralizing antibody;nonhuman primate;novel vaccines;Oncogenic;Oryctolagus cuniculus;Outcome;Pattern;permissiveness;Persons;Phase I Clinical Trials;placebo group;Polyvalent Vaccine;Population;pre-clinical;prevent;Preventive vaccine;primary effusion lymphoma;Primary Infection;Property;prophylactic;Regimen;Research;response;Route;Safety;Saliva;Seroprevalences;Subunit Vaccines;success;Tacrolimus;Testing;Time;Transplant Recipients;United States National Institutes of Health;unvaccinated;Vaccination;vaccine candidate;vaccine development;vaccine evaluation;Vaccines;vector;Viral;Viral Proteins;Viremia;Virus Diseases;Virus-like particle;Wild Type Mouse

PROJECT_TITLE: KSHV Subunit Vaccine Candidates to Elicit Potent Humoral Immune Reponses against KSHV Infection

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


ADMINISTERING_IC: AR

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Clinical Research;Genetics;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Wound Healing and Care

ORG_CITY: DURHAM

ORG_COUNTRY: UNITED STATES

ORG_DEPT: SURGERY

ORG_FIPS: US

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Zebrafish exhibit a remarkable ability to regenerate complex tissues such as heart and spinal cord. This project examines the molecular mechanisms of skin regeneration in zebrafish, particularly the central process of re- epithelialization, in order to develop novel regenerative strategies for human wound healing. A career development plan is proposed that supports the transition of the applicant, a plastic and reconstructive surgeon with a background in biomedical engineering, to an independent investigator in this field.

PI_NAMEs: BROWN, DAVID ANDREW (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: appendage;Award;Basal Cell;Behavior;Biological Assay;Biomedical Engineering;career;career development;Cell Cycle Progression;Cells;Chromatin;chronic wound;Complex;Data;Defect;design;Development;Development Plans;Developmental Biology;Doctor of Medicine;Doctor of Philosophy;Educational Status;Elements;epidermal stem cell;Epidermis;epithelial wound;epithelium regeneration;Equilibrium;Event;Evolution;Exhibits;experimental study;Faculty;Future;Gene Expression;Gene Transfer Techniques;Genes;Genetic;genetic approach;Genetic Enhancer Element;genetic manipulation;genetic technology;Genetic Transcription;Genomics;Goals;Heart;Human;Image;Imaging technology;improved;in vivo;in vivo imaging;Individual;Innovative Therapy;insight;K-Series Research Career Programs;keratinocyte;Laboratories;Learning;Link;Mammals;Maps;Mediating;member;Mentorship;migration;Modeling;Molecular;Morphology;Natural regeneration;neonatal mice;novel;novel strategies;Nucleic Acid Regulatory Sequences;Optics;Organism;Pathway interactions;Pattern;Phylogenetic Analysis;Plastic Surgeon;Positioning Attribute;prevent;Process;programs;Proliferating;quantitative imaging;re-epithelialization;regenerative;regenerative approach;regenerative biology;regenerative therapy;Regulation;Regulatory Element;Research;Research Personnel;Resolution;Role;Scientist;Shapes;Signal Transduction;Site;Skin;Skin injury;skin regeneration;skin wound;Spinal Cord;Structure;Surgeon;Techniques;Testing;Tissue Engineering;Tissue Model;tissue regeneration;tissue repair;Tissues;tool;Training;Transcriptional Regulation;transcriptome sequencing;Transgenic Organisms;Universities;Work;wound;wound bed;wound healing;Wound models;Zebrafish

PROJECT_TITLE: Genetic approaches to skin regeneration in zebrafish

STUDY_SECTION: AMS

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Special Grants Study Section[AMS]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: MILWAUKEE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: A major clinical hurdle in the management of breast cancer is metastatic progression and the development of resistance to conventional therapy. Our current proposal aims provides a deeper understanding of metastasis and identifies novel approaches to therapy.

PI_NAMEs: MILLER, TODD W. (contact)

PROGRAM_OFFICER_NAME: KAI, MIHOKO

PROJECT_TERMS: Address;Adjuvant;Adjuvant Chemotherapy;Attenuated;Automobile Driving;Basal Cell;Biological;Breast Cancer Cell;Breast Carcinoma;cancer cell;Cells;Cessation of life;chemotherapy;Chromatin;Cleavage Under Targets and Release Using Nuclease;Clinical;combinatorial;conventional therapy;Coupled;Cyclic AMP-Dependent Protein Kinases;Data;Disease Progression;Event;Gene Expression Profiling;Genes;Genetic;genetic evolution;Genetically Engineered Mouse;genome-wide;GTP-Binding Protein alpha Subunits, Gs;Habitats;Heterogeneity;in vivo;insight;Knock-in Mouse;Label;Malignant Breast Neoplasm;Malignant Neoplasms;Modeling;molecular subtypes;Mouse Mammary Tumor Virus;Mutation;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;Pattern;polyoma middle tumor antigen;Population;Primary Neoplasm;Process;programs;Property;Publishing;Recurrence;Recurrent tumor;Regimen;Relapse;Resistance development;response;Role;SOX4 gene;Testing;Therapeutic Uses;trait;transcriptomic profiling;Treatment Protocols;treatment response;tumor;tumor growth;tumor heterogeneity;tumor initiation;tumor microenvironment;tumor progression;Tumor-Associated Process;tumorigenesis;Work

PROJECT_TITLE: Uncovering the basis and implications of lineage plasticity in breast cancer

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Arthritis;Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Osteoarthritis

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: RELEVANCE (See instructions): We will continue to study the role of mitochondrial DNA metabolism in NLRP3 inflammasome activation and the effect of NRF2 on macrophage polarization. We will examine whether the pathogenesis of osteoarthritis (OA) and Alzheimer’s disease (AD) in mice is accompanied by oxidized mitochondrial DNA generation, its cleavage and export to the cytosol. We will also test the ability of CMPK2 and Fen1 inhibitors to attenuate NLRP3 inflammasome activation in OA, AD and other disease models.

PI_NAMEs: KARIN, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: MALLIA, CONRAD M

PROJECT_TERMS: Ablation;Acceleration;Acids;adduct;Agonist;aluminum sulfate;Alveolar Macrophages;Alzheimer's Disease;Alzheimer's disease risk;Anabolism;apolipoprotein E-4;Attenuated;attenuation;Base Excision Repairs;Binding;Binding Sites;brain tissue;CASP1 gene;Cerebrospinal Fluid;Chronic;Circulation;cyclopentanone;Cysteine;cytokine;Cytoplasm;Cytosol;Degenerative Disorder;Degenerative polyarthritis;Deoxyguanosine;Development;Disease;disease model;Disease Progression;DNA metabolism;Electron Transport;endonuclease;Enzymes;experimental study;Exposure to;Generations;Genes;Genetic Transcription;Human;Hydroxyapatites;IL18 gene;Impaired cognition;in vitro Assay;in vivo;Incidence;Inflammasome;Inflammation;Inflammatory;inhibitor;Inner mitochondrial membrane;Instruction;Interleukin-1 beta;Interleukin-10;IRF1 gene;knock-down;Knock-in;Knock-in Mouse;Knock-out;Knockout Mice;Lead;Ligands;Lung Adenocarcinoma;Macrophage;Maps;Mediating;Metabolism;Microglia;Mitochondria;Mitochondrial DNA;mitochondrial metabolism;Modeling;mouse model;Mus;Mutant Strains Mice;Nerve Degeneration;neutralizing antibody;NF-kappa B;nuclease;OGG1 gene;Outcome;Outer Mitochondrial Membrane;oxidation;Pathogenesis;Pathway interactions;Pharmaceutical Preparations;Play;Predisposition;prevent;Production;Prostaglandins;Regulation;repair enzyme;response;Rheumatoid Arthritis;Role;Severity of illness;Signal Transduction;Smoker;Specimen;Structure;Testing;Therapeutic Intervention;Time;Tissues;TNF gene

PROJECT_TITLE: NF-kappaB and Mitochondrial Signals as Positive and Negative Regulators of Inflammation

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Clinical Research;Kidney Disease;Osteoporosis;Physical Injury - Accidents and Adverse Effects;Prevention;Women's Health Research

ORG_DEPT: ORTHOPEDICS

PHR: PROJECT NARRATIVE In chronic kidney disease, fracture is common and morbid, but with complex pathophysiology that is often difficult to detect. Bone biopsy at the iliac crest is the gold standard method to evaluate bone pathology, but is infrequently available to clinicians, and is poorly correlated with other bone sites. We propose to evaluate bone pathology at the hip in kidney patients who undergo surgical repair for a hip fracture to determine the risk factors for different bone pathologies, biomarkers that can identify these pathologies non-invasively, and test the significance of these biomarkers for future fracture risk.

PI_NAMEs: HUGHES-AUSTIN, JAN MARIE (contact)

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TERMS: Admission activity;Age;Age-Related Osteoporosis;Alternative Therapies;Anatomy;Biological Markers;Biology;biomarker panel;Biopsy;bisphosphonate;bone;Bone Density;Bone Diseases;bone metabolism;Bone structure;Bone Tissue;bone turnover;Chronic Kidney Failure;Clinical;clinically relevant;community living;Complex;conventional therapy;cost;Data;Diabetes Mellitus;Dialysis patients;Disease;Evaluation;experience;FDA approved;fibroblast growth factor 23;Fracture;fracture risk;Frequencies;Functional disorder;Future;General Population;high risk;hip bone;Hip Fractures;Hip region structure;human old age (65+);Hyperparathyroidism;imaging modality;improved;Individual;Kidney;kidney imaging;Lesion;Low Prevalence;Measures;Medical center;Metabolic Bone Diseases;Methods;mineralization;Morbidity - disease rate;mortality;Multicenter Studies;Older Population;older women;Operative Surgical Procedures;osteoporosis with pathological fracture;Participant;Pathology;patient subsets;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Prevalence;prevent;Prospective Studies;PTH gene;repaired;Risk Factors;Serum;Site;Specialized Center;specific biomarkers;Specificity;Specimen;Testing;Time;Vision;Women's cohort

PROJECT_TITLE: Hip Fracture Pathology in Chronic Kidney Disease

STUDY_SECTION: SBDD

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_DEPT: OTHER BASIC SCIENCES

PHR: PROJECT NARRATIVE Wnt signaling is a critical regulator of development, and de-regulation of this pathway results in severe developmental defects, loss of tissue homeostasis and cancer. The proposed research will advance our understanding of Wnt signaling by generating and characterizing new tools to manipulate this pathway in human pluripotent stem cells, organoid cultures and whole animals. The long-term goal of these studies is to gain a better understanding of how Wnt signaling controls embryonic development, thereby enabling strategies for the generation of mature cells types, tissues and organs.

PI_NAMEs: WILLERT, KARL H (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Address;Adopted;Agonist;Animals;Anterior;Biochemical;Biological;Cell Communication;cell type;Cells;cellular engineering;Clinical;Complex;Congenital Abnormality;Defect;Development;Developmental Process;Disease;Embryo;Embryonic Development;Engineering;Event;Evolution;Exhibits;experimental study;Family;FZD1 gene;Generations;Goals;Heart;Homeostasis;Human;human pluripotent stem cell;In Vitro;in vivo;Individual;innovative technologies;Laboratories;Life;Malignant Neoplasms;mammalian genome;Methods;mimetics;Mus;novel therapeutics;Organ;Organism;Organoids;Output;Pathway interactions;Population;Property;Reagent;receptor;Research;Role;side effect;Signal Transduction;Specific qualifier value;Specificity;Stem Cell Research;stem cell self renewal;stem cells;Technology;Testing;Therapeutic;Tissue Engineering;Tissues;tool;tool development;WNT Family Gene;Wnt proteins;WNT Signaling Pathway

PROJECT_TITLE: Exploring Wnt-Fzd signaling specificities

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


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Basal-like breast cancer has the worst prognosis of all breast cancer types. One of the hurdles to identifying effective targeted therapies is the uncertainty about how the disease arises in the first place. By examining cancer-prone tissues before tumor onset, we hope to identify the path(s) that cells take en route to becoming a basal-like cancer.

PI_NAMEs: JANES, KEVIN A (contact);ZONG, HUI

PROJECT_TERMS: African American population;Appearance;B-Lymphocytes;BRCA1 gene;Breast;Breast Cancer Genetics;Breast conservation;breast stem cell;breast tumorigenesis;cancer cell;cancer type;Carcinoma;cell type;Cells;Chronology;Clonal Expansion;Collaborations;Data;Disease;Dissociation;Duct (organ) structure;Ecosystem;Endowment;Epithelial Cells;Event;extracellular;functional loss;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Predisposition to Disease;Genetic Transcription;Genetically Engineered Mouse;Genomics;Germ-Line Mutation;Gland;Goals;Heterogeneity;Human;Immune;immune cell infiltrate;Immune system;In Situ;In Situ Lesion;in vivo;Individual;innovation;Intervention;Knock-out;Label;lead candidate;Lesion;Lymphoid Cell;Macrophage;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary gland;Measures;Mediating;member;Methods;Mitosis;Molecular;mosaic;mosaic analysis;Mus;mutant;Myeloid Cells;Neoplasm Metastasis;neoplastic cell;Noninfiltrating Intraductal Carcinoma;novel;Null Lymphocytes;Oncogenic;Organoids;paracrine;pharmacologic;Phenotype;Play;premalignant;Premalignant Cell;Prevention;Preventive therapy;progenitor;Prognosis;Puberty;Receptor Protein-Tyrosine Kinases;recruit;Role;Route;Signal Transduction;Somatic Mutation;Statistical Data Interpretation;Stress;success;T-Lymphocyte;targeted treatment;Testing;Tissues;TNF gene;tool;TP53 gene;transcription factor;transcriptome;transcriptomics;Trees;tumor;tumor initiation;tumor progression;Tumor Suppressor Proteins;tumorigenesis;Uncertainty;Variant;Visualization;Woman;Work

PROJECT_TITLE: A premalignant chronology of cell-state variability in basal-like breast cancer

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


NIH_SPENDING_CATS: Cancer;Clinical Research;Prostate Cancer;Urologic Diseases

ORG_CITY: CORAL GABLES

ORG_DEPT: UROLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Narrative All current hormonal treatments for advanced prostate cancer target androgens or their action. Although initially effective, these treatments eventually fail because androgens are regenerated, stimulating tumor cell growth. Our data suggest tumors regenerate androgens by using a previously unrecognized pathway that is not affected by current treatments; this project will determine the role of this alternative pathway and is expected to lead to an entirely new prostate cancer treatment.

PI_NAMEs: SHARIFI, NIMA  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: abiraterone;Adrenal Glands;advanced prostate cancer;androgen biosynthesis;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;Androgens;antagonist;Anti-androgen Therapy;Binding;Biochemical Pathway;Bypass;Cancer Etiology;Castration;cell growth;Cell Nucleus;Cessation of life;Cholesterol;Clinical Data;Clinical Research;CYP17A1 gene;Data;Detection;Discrimination;Disease;docetaxel;Drug resistance;enzalutamide;enzyme activity;Enzymes;Generations;Goals;Hormonal;hormone therapy;Hydroxysteroid Dehydrogenases;Hyperactivity;inhibitor;innovation;intratumoral androgen;ionization;Malignant neoplasm of prostate;Maps;Mass Spectrum Analysis;Medical Castration;Medical Genetics;men;Metabolic;Methodology;Methods;Modeling;Natural regeneration;neoplastic cell;new therapeutic target;next generation;novel;Pathway interactions;Patients;pharmacologic;phase III trial;Phosphorylation;Phosphorylation Site;Physiological;Prostate;Prostate Cancer therapy;Resistance;Resistance development;Role;Serum;Stanolone;Steroid biosynthesis;Steroids;Testis;Testosterone;therapy resistant;tumor;Work

PROJECT_TITLE: CYP17A1-independent androgen synthesis and prostate cancer resistance to next-generation hormonal therapy

STUDY_SECTION: DMP

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


ADMINISTERING_IC: TW

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Clinical Research;Dissemination and Implementation Research;HIV/AIDS;Infectious Diseases;Mental Health;Pediatric;Women's Health Research

ORG_CITY: SEATTLE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: NARRATIVE The proposed program will train researchers at the Kenya Medical Research Institute (KEMRI) and the Ministry of Health (MOH) to conduct locally relevant research that will improve the lives of adolescent girls and women affected by HIV in Kenya and other parts of sub-Saharan Africa. Research will be focused on finding ways to implement interventions that have been proven to work and can directly lead to changes in guidelines, clinical practices and policies. Building capacity at KEMRI and MOH to conduct implementation research will have a long-term benefit for girls and women at highest risk for HIV acquisition.

PI_NAMEs: BUKUSI, ELIZABETH ANNE;FARQUHAR, CAREY  (contact)

PROGRAM_OFFICER_NAME: BANSAL, GEETHA PARTHASARATHY

PROJECT_TERMS: Address;Adolescent;Africa South of the Sahara;Caring;clinical practice;Communities;community engagement;Country;County;Distance Learning;Doctor of Philosophy;Education;Educational Status;Educational workshop;Ensure;Epidemic;Epidemiologist;Epidemiology;Face;Female Adolescents;Foundations;Funding;global health;Goals;Grant;Guidelines;Gynecologist;Health;Healthcare;high risk;HIV;HIV Infections;implementation science;improved;Infection;innovation;Kenya;Manuscripts;Medical Research;Medicine;member;Outcome;Persons;Policies;Preparation;prevent;Prevention;professor;programs;Public Health Schools;Research;Research Institute;Research Personnel;research to practice;service delivery;symposium;Training;Training Programs;Translational Research;Universities;Vulnerable Populations;Washington;Woman;Writing;young woman

PROJECT_TITLE: Women and HIV: Translation of Research into Practice


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Substantial research evaluates the contribution of one’s personal socio-economic status (SES) on risk for Alzheimer’s disease and related dementias (ADRDs) and outcomes after the onset of ADRDs, although in many global settings, adult children may be their older parents’ most critical socio-economic resource. In this project, we will evaluate the impact of adult children’s education on parents’ cognitive decline, risk for dementia/cognitive impairment, and on longevity, physical functioning, and psychosocial outcomes for older parents after dementia/cognitive impairment onset using data on over 156,000 older adults from global aging cohort studies representing 20 countries in North and Central America, Asia, and Europe. We will additionally evaluate the economic and non-economic factors that explain any apparent associations, and how these associations differ for subgroups of older adults, including by their own level of educational attainment and features of their country’s social policies.

PI_NAMEs: TORRES, JACQUELINE MARIE (contact)

PROGRAM_OFFICER_NAME: BRAUDT, DAVID BRUCE

PROJECT_TERMS: Adult;Adult Children;Aging;Alzheimer's disease related dementia;Alzheimer's disease risk;Asia;Behavioral;Central America;Characteristics;Child;Cognitive;Cognitive aging;cognitive impairment no dementia;cohort;Cohort Studies;Complement;Country;Data;data harmonization;Dementia;dementia burden;dementia care;dementia risk;Diagnosis;Disadvantaged;Disparity;econometrics;Economics;Education;Educational Status;Epidemiology;Europe;Family;Family Sizes;family structure;Future;Gender;Goals;Health;Health behavior;health care availability;Heterogeneity;Impaired cognition;improved;improved outcome;Individual;Intervention;Investments;late life;Laws;Literature;Longevity;Measures;Mediation;Mediator;Mental Health;Methodology;Methods;modifiable risk;mortality;mortality risk;National Institute on Aging;Natural experiment;North America;older adult;Outcome;parental influence;Parents;Pathway interactions;Personal Satisfaction;Pharmacological Treatment;physical conditioning;Physical Function;Play;Population;Population Research;Prevention;Probability;psychologic;psychosocial;psychosocial outcome;Quasi-experiment;Research;residence;Resources;Respondent;Risk;Risk Reduction;rural residence;Schools;Social Policies;Socioeconomic Status;socioeconomics;Subgroup;Testing;theories;Variant;welfare

PROJECT_TITLE: The contribution of adult child socio-economic status to parents' risk and outcomes of Alzheimer's disease and related dementias (ADRDs) in cross-national settings

STUDY_SECTION: SSPB

STUDY_SECTION_NAME: Social Sciences and Population Studies B Study Section[SSPB]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: BALTIMORE

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: Acute Respiratory Distress Syndrome (ARDS) is a serious complication of injuries and infections, including influenza, COVID-19, and future viruses, and has a high rate of death and disability. There are no effective medications available to treat ARDS. We used a computer to help identify potential new drugs to treat ARDS called substrate- and function-selective p38 inhibitors. We previously identified one of these inhibitors, UM101, which had lung-protective activity. We then modified this compound to improve its lung protective effects and started clinical testing. We have now identified four new compounds with much better effects than our original. We will modify these new compounds as we did for UM101 and test them for lung- protective effects to develop a pipeline of potential lung-protective drugs. Relevance to VA: The Veteran patient population is older and has many of the recognized risk factors for death from ARDS (influenza- and COVID-19-induced ARDS).

PI_NAMEs: HASDAY, JEFFREY D (contact)

PROJECT_TERMS: 2019-nCoV;Acute Lung Injury;Acute Respiratory Distress Syndrome;Address;Affect;Affinity;analog;Anti-Inflammatory Agents;Antiinflammatory Effect;aqueous;Aspartate;Award;Binding;Binding Proteins;Biological;Biological Assay;Biological Sciences;Bleomycin;Blood Vessels;candidate identification;Catalytic Domain;Cell model;Cells;Cessation of life;Chemicals;Chronic lung disease;Clinic;Clinical Trials;Collaborations;Complication;Computer Assisted;Computers;COVID-19;COVID-19/ARDS;cytokine;Databases;Death Rate;design;Development;Diabetes Mellitus;disability;Docking;Dose;drug candidate;Drug Design;drug development;Drug Kinetics;Effectiveness;efficacy testing;Endothelium;epithelial injury;Exhibits;Fever;Formulation;Funding;Future;Generations;Glutamates;Goals;Heart Diseases;Human;human old age (65+);Hypertension;Hyperthermia;improved;In Vitro;in vivo;in vivo evaluation;Induced Hyperthermia;Infection;Inflammation;Inflammatory;Influenza;inhibitor;Injury;kinase inhibitor;Lead;Legal patent;Licensing;Lung;lung injury;Maps;Maryland;Mitogen-Activated Protein Kinase Inhibitor;Mitogen-Activated Protein Kinases;Mitogens;Modeling;Modification;Molecular;Monkeys;Morbidity - disease rate;mouse model;multimodality;Mus;novel;novel therapeutics;Obesity;Outcome;p38 Mitogen Activated Protein Kinase;Pathogenicity;Pathway interactions;patient population;Patients;Permeability;Pharmaceutical Chemistry;Pharmaceutical Preparations;Pharmacodynamics;pharmacologic;Pharmacy Schools;Phase;phosphoproteomics;Phosphotransferases;Plasma;Preclinical Testing;Preparation;Process;Program Development;Property;Protective Agents;protective effect;Protein Kinase;Protein phosphatase;pulmonary artery endothelial cell;Rattus;receptor;receptor binding;research clinical testing;Research Personnel;respiratory virus;Risk Factors;RPS6KA5 gene;Safety;safety study;scaffold;screening;Services;Signal Transduction;Site;Solubility;Specificity;stress activated protein kinase;Surface Plasmon Resonance;Survivors;Testing;Therapeutic;therapeutic candidate;therapeutic target;Thrombin;Toxic effect;Universities;Veterans;Virus;Work

PROJECT_TITLE: Development of Novel Second Generation Anti-inflammatory Substrate-selective p38 MAP Kinase Inhibitors as Therapy for Acute Respiratory Distress Syndrome


ORG_CITY: CHARLESTON

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

ORG_STATE: SC

PHR: More than 7% of the US population and 20% of our Veterans have diabetes. Diabetes increases the risk of stroke and dementia, both of which are leading causes of disability. However, we do not know why. We think diabetes impairs the overall health of cells that line up the blood vessels in the brain. When this happens, other cells in the brain are affected and cannot function well. This project will determine how we can improve the health of small vessels in the brain and whether this improves stroke outcomes and dementia by using innovative therapies that can be easily implemented in patients. Thus, the results are expected to have a significant impact on human health and the VA mission.

PI_NAMEs: ERGUL, ADVIYE  (contact)

PROJECT_TERMS: Address;Affect;American;Anti-Inflammatory Agents;Apoptotic;arteriole;autocrine;Behavior;Blood Vessels;Brain;brain endothelial cell;Brain Injuries;Brain-Derived Neurotrophic Factor;brain-derived neurotrophic factor precursor;cardiometabolic risk;Caring;Categories;Cell Aging;Cell Line;Cell Survival;Cells;cerebrovascular;Cerebrovascular system;Cerebrum;Chronic;Cilostazol;Clinical;Clinical Trials;Cognition;Cognitive;Cognitive deficits;comorbidity;comparative;Complex;cost;Creativeness;Cytometry;Dementia;Demyelinations;Development;Diabetes Mellitus;diabetic;diabetic rat;disability;Disease;disease model;Down-Regulation;effective therapy;Endothelium;Evolution;Exhibits;experience;Experimental Diabetes Mellitus;experimental study;Female;Foundations;Functional disorder;Funding;gliovascular;glymphatic system;Health;Human;hyperphosphorylated tau;IL1R1 gene;Image;Impaired cognition;Impairment;improved;Inflammasome;Inflammation;Inflammatory;inhibitor;Injury;innovation;Innovative Therapy;Institution;Interleukin-1;Interleukin-1 beta;Ischemic Brain Injury;ischemic injury;knock-down;Knowledge;Long term disability;Magnetic Resonance Imaging;male;Mediating;Microglia;Mission;mixed dementia;Molecular;nanoparticle;Nerve Degeneration;Nervous System Disorder;neural;Neuroglia;Neurons;neuroprotection;NGFR Protein;Outcome;Pathology;Patients;Pericytes;phosphoric diester hydrolase;Phosphotransferases;Population;post stroke;post stroke cognitive impairment;premature;prevent;Prevention trial;Property;Rattus;receptor;Research;Risk;Risk Factors;Role;senescence;senomorphic;Severities;sex;Specificity;Stress;Stroke;stroke event;stroke outcome;stroke patient;stroke risk;stroke survivor;Structure;tau Proteins;tau-1;Testing;Therapeutic;therapeutically effective;Tyrosine Phosphorylation;vascular cognitive impairment and dementia;Vasodilator Agents;Veterans

PROJECT_TITLE: Cerebral Arteriole Structure/Function in Diabetic Ischemic Brain Injury


ORG_CITY: PORTLAND

ORG_NAME: PORTLAND VA MEDICAL CENTER

ORG_STATE: OR

PHR: For centuries, malaria has been considered a significant threat to the health and effectiveness of military forces that conduct operations in malaria-endemic areas. In modern times, malaria remains a major medical threat to U.S. military capability for operations in any environment where malaria is endemic, to be specific, the developing tropical and subtropical regions of the world. Malaria and antimalarials represent two of the most common biological and chemical exposures of US veterans. Our drug development project strongly aligns and compliments with the VA’s mission to improve Veterans’ well-being through supporting/conducting preclinical research. We seek to develop safe and effective antimalarials that can be used in all individuals, including our military service men and women. The resultant advantages of avoiding drug toxicity, febrile illness and complex medical management during deployment are self-evident, as are the benefits to both short and long-term health of the soldiers.

PI_NAMEs: KELLY, JANE X (contact)

PROJECT_TERMS: Address;Ames Assay;Anti-malarials;Area;Binding;Biological;Biological Assay;Blood;Caco-2 Cells;Cardiotoxicity;Chemical Exposure;chemical synthesis;Complex;Cytochrome P450;cytotoxicity;design;Disease;DNA analysis;Dose;Drug Combinations;drug development;Drug Interactions;Drug Kinetics;Drug resistance;Drug Targeting;Drug toxicity;Effectiveness;Environment;Evaluation;Fever;genome analysis;genome sequencing;Genomic DNA;Goals;Health;Heme;HepG2;Human;improved;In Vitro;in vivo;Individual;Infection;innovation;Isoenzymes;iterative design;Lead;lead candidate;lead optimization;Liver Microsomes;Malaria;Measures;Medical;men;Metabolic;metabolic profile;Methods;Microsomes;Military Personnel;military service;Mission;Modeling;Modernization;Molecular;Molecular Target;Monitor;Multi-Drug Resistance;Mus;new combination therapies;novel;novel strategies;operation;Parasite resistance;Parasites;patch clamp;Permeability;Personal Satisfaction;Pharmaceutical Preparations;Pharmacology;Plasmodium;Plasmodium falciparum;Plasmodium yoelii;pre-clinical assessment;pre-clinical research;preclinical safety;Preclinical Testing;prevent;programs;Research;Resistance;resistant Plasmodium falciparum;Rodent;Rodent Model;Safety;safety assessment;Salmonella typhimurium;single molecule;Soldier;synergism;Toxic effect;Toxicity Tests;trait;uptake;Vacuole;Validation;Veterans;whole genome;Woman;Work

PROJECT_TITLE: Novel Synergistic Antimalarials with Resistance Reversal Function


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: CHICAGO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative Preliminary experiments in the non-human primate model revealed that most of the detected SIV infected cells during the rebound phase after antiretroviral treatment interruption are of myeloid origin. The possible dependence of the reservoir on myeloid cell infection represents a previously unknown observation and needs further exploration to understand the mechanism of viral rebound and design successful strategies for HIV-1 cure.

PI_NAMEs: HOPE, THOMAS  (contact);LORENZO-REDONDO, RAMON ;MARTINELLI, ELENA

PROGRAM_OFFICER_NAME: RAO, VASUDEV RAMACHANDRA

PROJECT_TERMS: adaptive immune response;Adaptive Immune System;Anatomy;Animals;Anti-viral Agents;Anti-viral Response;Antibody Response;antiretroviral therapy;Area;Autopsy;Bar Codes;Binding;Biological Assay;Blood;Brain;CD3 Antigens;CD4 Positive T Lymphocytes;Cell Separation;cell type;Cells;Cellular Morphology;Characteristics;Dependence;design;Down-Regulation;emerging virus;Environment;Event;Excision;experimental study;fitness;HIV;HIV-1;Human;Image;Immune;Immune response;Individual;Infection;Innate Immune Response;Innate Immune System;innovation;insight;Interferons;Interruption;Intervention;Kinetics;Label;Lead;Light;Location;Macaca;Macaca mulatta;Mediating;Methodology;Microglia;Modeling;Morphology;Myelogenous;Myeloid Cells;Names;Nature;Negative Staining;nonhuman primate;Operative Surgical Procedures;PET/CT scan;Phase;Play;Population;Population Dynamics;pressure;Process;Property;Recovery;Reproducibility;Research;response;Role;Running;Shapes;Signal Transduction;Site;SIV;Source;spatial relationship;success;Systemic infection;T-Lymphocyte;Thinking;Time;Tissue Sample;Tissues;Transmission Electron Microscopy;Variant;Viral;viral rebound;Viral reservoir;Viremia;Virion;Virus;Visualization;Work

PROJECT_TITLE: Role of myeloid cells in CNS and systemic reservoirs and rebound

STUDY_SECTION: HVCD

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


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Infectious Diseases;Lung;Microbiome;Otitis Media;Pediatric;Pneumonia;Pneumonia and Influenza

ORG_CITY: Aurora

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative This proposal addresses the significant clinical issue of bacterial otitis media (OM). We developed a new mouse model to investigate how specific host innate immune responses and the microbiome impact clearance of the major OM pathogen Streptococcus pneumoniae following invasion of the middle ear. The goal of these studies is to identify critical factors which promote S. pneumoniae clearance from the middle ear in order to inform the development of novel immunotherapy and probiotic-based approaches for the treatment of bacterial OM.

PI_NAMEs: CLARK, SARAH E (contact)

PROGRAM_OFFICER_NAME: WATSON, BRACIE

PROJECT_TERMS: 6 year old;Address;age group;analog;Animal Model;Anti-Inflammatory Agents;Antibiotic Resistance;Antibiotic susceptibility;Antibiotics;cell type;chemokine receptor;Child;childhood hearing loss;Clinical;Clinical Management;clinically significant;co-infection;Corynebacterium;cytokine;Data;Defect;Development;Diagnosis;Disease;Double-Stranded RNA;economic impact;experimental study;Flow Cytometry;Goals;Growth;hearing impairment;Histology;Hospitals;host microbiome;IFNAR1 gene;IL8RB gene;Image;Immune;immune activation;Immunotherapy;improved;In Vitro;Infection;Inflammation;Inflammatory;Injections;Innate Immune Response;Integration Host Factors;Interferon Type I;Interleukin-10;Interleukin-8B Receptor;Invaded;Knock-out;Knowledge;Lung;Measures;Mediating;microbiome;middle ear;Modeling;mouse model;Mus;Myeloid Cells;Nasopharynx;neutrophil;Neutrophil Infiltration;next generation sequencing;novel;novel therapeutic intervention;Otitis Media;pathogen;Pathogenesis;pathogenic bacteria;pathogenic virus;Pathway interactions;Pneumococcal Infections;Poly I-C;Population;Predisposition;prevent;Probiotics;Process;Production;Proteins;recruit;Recurrence;recurrent infection;Reporting;Resistance;respiratory;response;Risk;Role;Signal Transduction;Site;Source;Stimulus;Streptococcus pneumoniae;Streptococcus pneumoniae plY protein;therapeutic target;Tissues;Upper respiratory tract;Vaccines;Viral;Virulence;Virus Replication;Visit;Wild Type Mouse

PROJECT_TITLE: Host factors influencing early clearance of Streptococcus pneumoniae from the middle ear following invasion from the nasopharynx

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;HIV/AIDS;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Disease

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

PHR: PROJECT NARRATIVE HIV/HBV co-infection is common due to highly similar routes of transmission. HIV/HBV co-infected patients are at higher risk for liver disease than HBV mono-infected patients. Here, we describe the first rhesus macaque model of HBV infection, setting the stage for a highly needed HIV/HBV co-infection primate model.

PI_NAMEs: BURWITZ, BENJAMIN J (contact)

PROGRAM_OFFICER_NAME: RADKE, JOSHUA BRYAN

PROJECT_TERMS: Acceleration;acute infection;Adenoviruses;Adolescent;Adult;Africa South of the Sahara;Animal Model;Animals;Blood;Cause of Death;CD8-Positive T-Lymphocytes;Cells;Chronic;Chronic Hepatitis B;chronic infection;Circular DNA;Clinical;co-infection;Codon Nucleotides;cohort;constriction;design;DNA;Ducks;effector T cell;Ensure;exhaustion;experience;Frequencies;gene therapy;genetic manipulation;Genome;Genomics;global health;HBV Genotype;HBV Liver Disease;Health;Hepatitis B Acquisition;Hepatitis B Infection;Hepatitis B Virus;Hepatocyte;high risk;HIV;HIV Infections;Human;Immune;immunodeficiency;Immunosuppression;in vivo;Individual;Infection;Intravenous;Liver;liver biopsy;Liver diseases;Liver Dysfunction;Liver Fibrosis;Macaca;Macaca mulatta;Modeling;Monitor;Mus;nonhuman primate;novel;Pan Genus;Pathogenesis;Patients;Persons;Physiological;polypeptide;Positioning Attribute;Prealbumin;Prevalence;prevent;Primary carcinoma of the liver cells;Primates;Probability;promoter;receptor;Regimen;Research;Route;Sampling;Serotyping;Serum;SIV;Southeastern Asia;Structure;Surface Antigens;T cell response;T-Lymphocyte;Taurine Cholate;Techniques;Testing;Time;Tissues;Transgenic Organisms;transmission process;Transplantation;vector;Viral Load result;Viral Vector;Viremia;Virion;Virus;Woodchuck;Work

PROJECT_TITLE: A Rhesus Macaque Model of HIV and HBV co-infection

STUDY_SECTION: HCAC

STUDY_SECTION_NAME: HIV Coinfections and HIV Associated Cancers Study Section[HCAC]


ADMINISTERING_IC: FD

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: Champaign

ORG_NAME: ASSOCIATION OF AMERICAN FEED CTRL OFFS

PHR: Project Narrative AAFCO Advanced Inspector Training Seminar Application PAR-19-306 Funding from this grant will allow the Association of American Feed Control Officials (AAFCO) to host an annual Advanced Inspector Training Seminar. This seminar provides informative feed regulatory presentations, interactive demonstrations such as emergency response tabletop exercise, and professional instructor led training by the Council on Licensure Enforcement and Regulation (CLEAR) in professionalism topics, including, investigative techniques, evidence collection, and report writing, that have been specifically designed for animal feed regulatory personnel.

PI_NAMEs: FERGUSON, ASHLEE-ROSE  (contact)

PROGRAM_OFFICER_NAME: WEBB, SUZANNE


ORG_NAME: CLEMENT J. ZABLOCKI VA MEDICAL CENTER

PHR: Our military Veterans disproportionately suffer from breathing-related diseases that result in persistently increased levels of carbon dioxide (CO2) in the body (chronic hypercapnia). The chronic hypercapnia alone may lead to poor quality of life, reduced life expectancy, and decreased neurologic (cognitive) function, and can become worse when patients acquire an acute illness. Yet, little is known about how the breathing and the brain progressively adapt to chronic hypercapnia. Here, we will utilize a human-like animal model (goats) and apply cutting-edge approaches to measure changes in gene expression within the brain that are altered during different stages of chronic hypercapnia, how these gene expression patterns may be further altered when the hypercapnia is made worse, and if brain inflammation plays an important role in the adaptive response to hypercapnia. This approach will provide unprecedented insights into critical signaling pathways in the brain that are altered during hypercapnia, and thus provide new targets for therapeutic intervention in patients suffering from these diseases.

PI_NAMEs: FORSTER, HUBERT V (contact)

PROJECT_TERMS: Acids;Acute;Adult;Animal Model;base;Bicarbonates;Blood Pressure;Brain;Brain Stem;Breathing;Carbon Dioxide;Cell Nucleus;cell type;Cells;Chronic;Chronic lung disease;Clinical;Cognition;Cognitive;cognitive control;cognitive function;Data;Death Rate;differential expression;Disease;Electrolytes;Encephalitis;Exposure to;Future;Gases;Gene Expression;Gene Expression Profile;Genes;Glutamate Receptor;Goals;Goat;Heart Rate;Hour;Human;Hypercapnia;Hyporeflexia;Impaired cognition;Impairment;insight;Interleukin-1 beta;Interleukins;Intervention;Kidney;Knowledge;Life Expectancy;Measures;Mental Depression;Metabolic;metabolic rate;Methodology;military veteran;Modeling;Molecular;neural;Neurobiology;Neurologic;Neuromuscular Diseases;Neuronal Plasticity;Neurons;neurotransmission;new therapeutic target;Nuclear RNA;Pathologic;Pathway interactions;patient population;Patients;Phosphorylation;Physiological;Physiological Adaptation;Play;Population Control;Potassium;Prognosis;Publishing;Quality of life;Rattus;Reflex action;Resolution;respiratory;response;Role;Serotonergic System;Serotonin;Signal Pathway;single nucleus RNA-sequencing;Site;Stimulus;System;Technology;Testing;Therapeutic Intervention;therapeutic target;Time;Tissues;transcriptome sequencing;United States Department of Veterans Affairs;ventilation;Work

PROJECT_TITLE: Mechanisms of Ventilatory Adaptations to Chronic Hypercapnia


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Eye Disease and Disorders of Vision;Genetics;Infectious Diseases;Neurosciences;Rare Diseases;Vector-Borne Diseases

ORG_CITY: SANTA BARBARA

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA BARBARA

PHR: Project narrative  The mosquito disease vector, Aedes aegypti, is troubling because it spreads viruses that cause diseases such as dengue, yellow fever, and Zika, which infect >100,000,000 people/year. Once this daytime biting mosquito senses CO2 from our breadth, they then home in on people using visual and other cues. Despite the importance of vision in finding humans, our understanding of the visual mechanisms that mosquitoes use to find people are largely unknown. The goal of this application is to fill this gap. This project lays the conceptual foundation for devising innovative approaches to limit the ability of mosquitoes in detecting hosts for blood meals.

PI_NAMEs: MONTELL, CRAIG  (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Address;Aedes;Aedes aegypti genome;Affect;Area;Behavior;Behavioral;Behavioral Assay;Behavioral Genetics;Binding;Biochemical;Biochemistry;Biological Assay;Biology;Bite;Blood;Brain;Carbon Dioxide;Cellular biology;circadian;circadian pacemaker;circadian regulation;Circadian Rhythms;climate change;Coupled;CRISPR/Cas technology;cryptochrome;Cues;Culicidae;Darkness;Data;Dengue;Development;Disease;Disease Vectors;Drosophila genus;egg;Electrophysiology (science);Electroretinography;Elements;Environmental Wind;Exhalation;Experimental Genetics;experimental study;Eye;Feedback;Female;fly;Foundations;Genes;genetic approach;Goals;Home;Homologous Gene;Human;innovation;insect disease vector;Insecta;interdisciplinary approach;Light;Location;Measures;meter;Modeling;Molecular;Molecular Genetics;Monitor;Mosquito Control;Mosquito-borne infectious disease;Mutagenesis;mutant;Mutate;Mutation;Mutation Analysis;Odors;olfactory stimulus;Organism;patch clamp;Peptides;Persons;Phase;Phospholipase;Phospholipase C;phospholipase C beta;Photoreceptors;Phototransduction;Proteins;Regulation;Research;response;Retina;Rhodopsin;Role;sensor;Sensory;sensory mechanism;Signal Transduction;Site;Skin;Stimulus;Testing;tool;Transgenic Organisms;Travel;TRP channel;United States;vector mosquito;viral transmission;Virus;Vision;Visual;Visual attention;visual information;Walking;Work;Yellow Fever;ZIKA

PROJECT_TITLE: Mechanisms of visual transduction and light-driven behaviors in Aedes aegypti

STUDY_SECTION: VB

STUDY_SECTION_NAME: Vector Biology Study Section[VB]


ADMINISTERING_IC: HD

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

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: Project Narrative Birth defects are a leading cause of death and morbidity in children around the world. The David W. Smith Workshop on Malformations and Morphogenesis has a history of being the primary forum where clinicians and basic scientists exchange information on the pathogenesis of human malformations. This proposal is a request to provide continuing support for the David W. Smith Workshop in the form of travel stipends for residents, fellows, junior faculty and a select number of plenary speakers.

PI_NAMEs: KRANTZ, IAN D. (contact)

PROGRAM_OFFICER_NAME: BARDHAN, SUJATA

PROJECT_TERMS: Adult;Affect;Atmosphere;Basic Science;Behavioral;Breathing;career;Cause of Death;Child;Childhood;Clinical;Cognitive;Collaborations;Congenital Abnormality;congenital anomaly;Development;Developmental Biology;developmental disease;disability-adjusted life years;Disease;Dysmorphology;Educational workshop;Embryology;Environment;Epidemiologist;Faculty;Family;Fathers;First Pregnancy Trimester;Funding;Genetic;Goals;Human;improved;Individual;Infant;Infant Mortality;Interdisciplinary Education;Interdisciplinary Study;interest;International;Intervention;malformation;Medical;medical specialties;meetings;Mentors;Mentorship;Morbidity - disease rate;Morphogenesis;mortality;neonate;next generation;Operative Surgical Procedures;Participant;Pathogenesis;Pathologist;premature;programs;psychologic;Recording of previous events;recruit;Research;Research Personnel;Respiratory distress;Scientist;Spontaneous abortion;stillbirth;Students;Talents;Term Birth;Training;Travel;Uncertainty;United States;Work

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Developmental Biology Study Section[CHHD-C]


ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative Function and regulatory mechanisms of the Wnt5a-Ror morphogenetic pathway PI: Ho Wnt5a-Ror signaling is an evolutionarily conserved developmental signaling pathway that controls cell and tissue morphogenesis. Genetic mutations that disrupt the pathway cause congenital birth defects. Our research aims to delineate the cell biological functions and regulatory mechanisms of the pathway and how these fundamental processes are perturbed in Wnt5a-Ror driven human diseases.

PI_NAMEs: HO, HSIN-YI HENRY (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Actomyosin;Address;Automobile Driving;Behavior;Behavioral;Binding Proteins;Biochemical;Biological Assay;Biological Process;Biomechanics;Canis familiaris;cell behavior;Cell Culture System;cell motility;Cell surface;Cells;Characteristics;Clinical;Complex;Congenital Abnormality;Congenital Disorders;Cytoplasm;Cytoskeleton;Cytosol;Defect;Development;Disease;DNA Sequence Alteration;Dsh protein;Elements;Exhibits;experimental study;Face;Genetic;Goals;Human;human disease;insight;interest;Knock-out;Ligands;Limb structure;Measurement;Mediating;Morphogenesis;Mutation;novel;Pathogenesis;Pathogenicity;Pathway interactions;pharmacologic;Phenotype;Physiological;Portraits;Process;Proteins;receptor;Regulation;Reporter;Research;Robinow syndrome;Role;Scaffolding Protein;Signal Pathway;Signal Transduction;Stress Fibers;Structure;three dimensional cell culture;Tissues;Transducers;transmission process;Vertebrates;WNT5A gene

STUDY_SECTION: MRAC

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Genetics;Hematology;Kidney Disease;Prevention;Rare Diseases;Sickle Cell Disease

ORG_CITY: MEMPHIS

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF TENNESSEE HEALTH SCI CTR

ORG_STATE: TN

PHR: Project Narrative African Americans with sickle cell disease (SCD) and co-existing kidney disease have an increased risk of mortality. Recent genetic studies have shown a causal association of apolipoprotein L1 gene (APOL1) polymorphisms with markedly increased risk for development of kidney disease in African Americans. The proposed research aims to 1) elucidate the association between APOL1 as well as other selected genetic modifiers in the development and progression of chronic kidney disease in individuals with SCD and 2) to generate a validated multi-gene genetic risk profile to identify individuals at increased risk of chronic kidney disease which will set the stage for future clinical studies evaluating novel disease-modifying therapies.

PI_NAMEs: ZAHR, RIMA  (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Address;Adult;Affect;African American population;Age;Albumins;Albuminuria;Alleles;alpha-Thalassemia;Apolipoproteins;beta Globin;biobank;Blood Vessels;BMP4;Candidate Disease Gene;career development;Caring;Chicago;Child;Childhood;Chronic Kidney Failure;Clinic;Clinical;clinical care;Clinical Markers;Clinical Research;cohort;Complex;Creatinine;Cross-Sectional Studies;Data;Death Rate;design;Development;Development Plans;Disease;efficacy evaluation;End stage renal failure;Enrollment;Epidemiology;experience;Functional disorder;Future;Gene Mutation;Genes;Genetic;genetic epidemiology;Genetic Polymorphism;Genetic Risk;genetic selection;Genetic study;genetic variant;genome wide association study;genomic data;Genomics;Glomerular Filtration Rate;Goals;GSTM1 gene;Health Sciences;Hematological Disease;Hemolysis;high risk;high risk population;Hypertension;Hypoxia;Illinois;improved;Individual;Inflammation;Injury to Kidney;innovation;intervention program;Kidney Diseases;Kidney Failure;Knowledge;life span;longitudinal analysis;Longitudinal cohort;Measures;Medical;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methods;Morbidity - disease rate;mortality;mortality risk;nephrogenesis;NMT2 gene;novel;Organ;Outcome;Oxidative Stress;Participant;Pathology;Patients;Pediatrics;Phenotype;polymerization;Polymers;prevent;professor;prospective;Prospective Studies;racial disparity;renal damage;Renal function;Renin-Angiotensin-Aldosterone System;Reporting;Research;research and development;Risk;Risk Factors;risk variant;Role;Route;Saint Jude Children's Research Hospital;Scientist;Sickle Cell;Sickle Cell Anemia;Sickle Hemoglobin;skills;Structural defect;Techniques;Tennessee;Testing;Thalassemia;Training;UMOD gene;Universities;Urine;Variant;VEGFA gene

PROJECT_TITLE: Genetic modifiers of Sickle Cell Kidney Disease

STUDY_SECTION: MPOR

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Brain Disorders;Cannabinoid Research;Drug Abuse (NIDA only);Endocannabinoid System Research;Epilepsy;HIV/AIDS;Infectious Diseases;Natural Products;Neurodegenerative;Neurosciences;Substance Misuse

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Public Health Relevance: HIV-1 Neurotoxicity: Mechanism & Modulation by Cannabinoids HIV-associated neurocognitive disorder (HAND) results from impaired synaptic communication. This proposal describes experiments to determine how the HIV protein Tat impairs the endocannabinoid system, an intrinsic mechanism that protects against excess excitatory synaptic activity. Studies that evaluate the consequences of these changes on network and cognitive function will guide the development of drugs to improve cognitive function in HAND and provide insight into potential untoward effects of marijuana in patients with HAND.

PI_NAMEs: THAYER, STANLEY A (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Acute;Affect;anti-epileptic agents;antiretroviral therapy;Astrocytes;Automobile Driving;Brain;Cannabinoids;Cells;Chronic;Clinical;clinical care;CNR1 gene;cognitive function;Communication;cytokine;Data;desensitization;Deterioration;Disease;Dominant-Negative Mutation;Doxycycline;drug development;Drug Targeting;Electroencephalography;Elements;endocannabinoid signaling;Endocannabinoids;endogenous cannabinoid system;epileptiform;Excitatory Synapse;excitotoxicity;exogenous cannabinoid;experience;experimental study;Exposure to;Foundations;Frequencies;frontal lobe;Funding;Glial Fibrillary Acidic Protein;Glutamates;Goals;Hippocampus;HIV;HIV tat Protein;HIV-1;HIV-associated neurocognitive disorder;human induced pluripotent stem cells;Immunohistochemistry;Impaired cognition;Impairment;improved;in vivo;Individual;Inflammatory;insight;knock-down;Link;Marijuana;Mediating;Microglia;Modeling;Molecular;Mus;Nature;Neurodegenerative Disorders;Neuroglia;neuroinflammation;Neurologic Deficit;Neurons;neurophysiology;neuroprotection;neurotoxicity;Neurotoxins;neurotransmission;neurotransmitter release;new therapeutic target;novel;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;presynaptic;Prevalence;Proteins;public health relevance;receptor function;Regulation;release factor;Risk;Role;Seizures;Signal Pathway;Slice;small hairpin RNA;Symptoms;Synapses;synaptic function;synaptic inhibition;Synaptic Transmission;System;targeted treatment;tat Protein;Testing;Therapeutic Intervention;Transgenic Mice;Work


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Genetics;Hepatitis;Hepatitis - C;Infectious Diseases;Liver Disease;Vector-Borne Diseases

ORG_CITY: DURHAM

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: DUKE UNIVERSITY

PHR: PROJECT NARRATIVE RNA viruses, such as hepatitis C virus (HCV) and dengue virus (DENV), encompass both established and emerging pathogens, and cause significant morbidity and mortality worldwide remaining a constant threat to global public health. The proposed study will define new host pathways exploited by RNA viruses such as HCV and DENV that could form the basis of new antiviral therapies to limit viral infection. In addition, it will describe new mechanisms of regulation of the RNA modification m6A that will enable new understanding into a host of human diseases that are caused by altered gene expression and regulated by RNA modifications.

PI_NAMEs: HORNER, STACY MICHELLE (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Anti-viral Therapy;Binding;Binding Proteins;Biology;cellular targeting;Complex;Core Protein;Cytoplasm;Data;Dengue Infection;Dengue Virus;emerging pathogen;Family;Family member;Flaviviridae;Flaviviridae Infections;Flavivirus;Funding;Gene Expression;Genome;Goals;Hepatitis C;Hepatitis C virus;human disease;Human papillomavirus 16 E1 protein;improved;Infection;innovation;Interferons;Mediating;Messenger RNA;Methylation;Methyltransferase;Modification;Molecular;Morbidity - disease rate;mortality;novel;Nuclear;Outcome;particle;Pathway interactions;Play;Production;protein complex;Proteins;Public Health;Reader;recruit;Regulation;Regulatory Pathway;response;RNA;RNA Binding;RNA methylation;RNA Stability;RNA Viruses;RNA-Binding Proteins;RNA-Protein Interaction;Role;Signal Pathway;Signal Transduction;Site;Structure;Testing;Translations;Viral;Viral Genome;Viral Packaging;Viral Physiology;viral RNA;Virion;Virus;Virus Diseases;Virus Replication;Work;Zika Virus

PROJECT_TITLE: Defining the role of the RNA modification N6-methyladenosine during Flaviviridae virus infection

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


NIH_SPENDING_CATS: Aging;Arthritis;Autoimmune Disease;Clinical Research;Genetics;Rheumatoid Arthritis

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: The immune system changes profoundly with progressive age, leaving the elderly susceptible to cancer, infection and tissue inflammation. Immune aging occurs prematurely in patients with rheumatoid arthritis and is associated with defects in DNA repair and with reprogramming of cellular metabolism. Here, we study the role of mitochondria and of mitochondrial DNA repair in immune aging.

PI_NAMEs: WEYAND, CORNELIA M. (contact)

PROGRAM_OFFICER_NAME: PRABHUDAS, MERCY R

PROJECT_TERMS: Acceleration;Acetyl Coenzyme A;adaptive immunity;Affect;Age;age related decline;aged;Aging;Autoimmune Diseases;Behavior;Behavioral;Bioenergetics;Biogenesis;Biological Models;Biological Process;CASP1 gene;Caspase;cell age;Cell Aging;Cell Compartmentation;Cell Death;Cell Reprogramming;Cell Survival;cell type;Cells;Cessation of life;Chimera organism;Chronic;Citric Acid Cycle;cohort;comparative;Complex;cytokine;Cytolysis;Cytoplasm;Data;Defect;Deoxyribonucleases;Deterioration;DNA;DNA Repair;Effector Cell;Elderly;Electron Transport;Elements;Engraftment;experimental study;Extracellular Space;Extravasation;frailty;Funding;gain of function;gene repression;Generations;Glucose;Glycolysis;Health;Human;IL18 gene;Immune;Immune system;Impairment;In Vitro;in vivo;Individual;Infection;Inflammasome;Inflammation;Inflammatory;Invaded;Life;lipid biosynthesis;Longevity;loss of function;Lytic;Malignant Neoplasms;Maps;Mediating;Membrane;Metabolic;Metabolism;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Modification;Molecular;mouse model;Natural Immunity;nuclease;Older Population;overexpression;oxidation;oxidative damage;Oxygen Consumption;Pathogenicity;Pathway interactions;Patients;Pentosephosphate Pathway;Peripheral;Phenotype;Predisposition;premature;prevent;Process;programs;Proteins;Proteolysis;Regulation;repaired;Repression;Resources;response;Rheumatoid Arthritis;Role;SCID Mice;Secure;Stress;Syndrome;Synovial Membrane;T-Lymphocyte;telomere;telomere damage;Testing;tissue injury;Tissues;trait;Translating;Vascular Endothelial Cell;Work

PROJECT_TITLE: DNA Repair and Mitochondrial Dysfunction in T Cell Aging


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Clinical Research;Infectious Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Aerosol-generating procedures are medical procedures that can potentially produce pathogen-laden aerosols that pose a risk to healthcare providers. This has become a signiﬁcant issue as a result of the COVID-19 pandemic, but it is crucial that the risks associated with speciﬁc procedures can be evaluated in a rigorous way not just for the current pandemic but for any future disease outbreaks as well. New tools are needed to assess these risks and develop mitigation strategies, and the primary focus of this exploratory project is to develop such a tool and use it to evaluate risk for several key procedures.

PI_NAMEs: HOWARD, NELSON SCOTT;SCHMIDT, BRYAN  (contact)

PROGRAM_OFFICER_NAME: ANDERSON, AFROUZ AZARI

PROJECT_TERMS: 2019-nCoV;Address;Aerosols;Air;Algorithms;Bypass;Clinical;Communicable Diseases;COVID-19 pandemic;current pandemic;Data;density;design;Dimensions;Disease Outbreaks;Evaluation;experimental study;Future;Goals;Health Personnel;Health protection;high risk;Human;Image;image processing;in vivo;indexing;Influenza;Intubation;Knowledge;Light;Lighting;Liquid substance;Manikins;Mechanics;Medical;Methods;novel;Optics;Oral cavity;pathogen;Patients;Pattern;portability;Procedures;prototype;Publishing;Research;Risk;Risk Assessment;risk minimization;risk mitigation;surgical mask;System;Techniques;Time;tool;Tracheostomy procedure;transmission process;ventilation;Virus Diseases;Visualization;Work

PROJECT_TITLE: Background Oriented Schlieren (BOS) Visualization for Evaluation of Risk in Aerosol-Generating Procedures

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


FUNDING_MECHANISM: OTHERS

ORG_CITY: ANN ARBOR

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: MI

PHR: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with increasing incidence in the veteran population. As the five-year survival rate for this disease remains extremely low, there is an urgent need to uncover the mechanisms underlying how pancreatic cancer cells become aggressive and resistant to standard therapies. PDAC is characterized by an abundant tumor microenvironment which supports resistance to chemotherapy. The tumor immune microenvironment, and myeloid cells in particular, have been highly implicated in chemoresistance. Utilizing pancreatic cancer patients at the Ann Arbor VA Healthcare System, this proposal aims to uncover the mechanisms of chemoresistance leveraging single-cell RNA sequencing, patient-derived organoid culture, and biospecimen acquisition of longitudinal matched human biospecimens to identify ways to treat therapy-refractory patients in this deadly disease.

PI_NAMEs: CARPENTER, EILEEN S (contact)

PROJECT_TERMS: Address;Aftercare;Aggressive behavior;Bioinformatics;Biological Models;Biometry;Biopsy;Blood;Cancer Etiology;career;Cell Separation;Cells;Cessation of life;Chemoresistance;chemotherapeutic agent;chemotherapy;Clinic;Clinical Data;Coculture Techniques;Consent;Cytometry;Data;Data Set;Development;Diagnosis;Diagnostic;Disease;Disease Outcome;Epithelial Cells;Excision;Fine-needle biopsy;genetic signature;Goals;Healthcare Systems;Heterogeneity;Human;IL8 gene;Immune;immune resistance;Immune response;Immune system;Immunofluorescence Immunologic;Immunotherapeutic agent;Impairment;In Vitro;Incidence;inhibitor;Legal patent;Ligands;Malignant neoplasm of pancreas;Mediating;military veteran;Mus;Myelogenous;Myeloid Cells;Myeloproliferative disease;neoplastic cell;novel;Operative Surgical Procedures;Organoids;outcome prediction;pancreatic cancer cells;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;Patients;Peripheral;peripheral blood;Peripheral Blood Mononuclear Cell;Play;precision medicine;Predisposition;programs;receptor;Refractory;Refractory Disease;Reporting;Research Personnel;Resistance;Resistance development;Resources;response;Role;Sampling;single cell sequencing;single-cell RNA sequencing;Site;Specimen;Survival Rate;System;Techniques;Testing;therapeutic target;Time;Tissues;Training;translational cancer research;Translational Research;Translations;treatment comparison;treatment response;tumor;tumor immunology;tumor microenvironment;Tumor Promotion;Tumor Tissue;tumor-immune system interactions;Veterans

PROJECT_TITLE: The Tumor Immune Microenvironment in Pancreatic Cancer Chemoresistance


ORG_CITY: MATHER

ORG_NAME: VA NORTHERN CALIFORNIA HEALTH CARE SYS

PHR: Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer, which is the leading cause of cancer- related deaths in the US veterans and general population. Molecularly targeted therapy and immunotherapy are two recent major breakthroughs in NSCLC. Each treatment modality benefits about 20% of NSCLC patient populations that can be enriched by a molecular or immunologic biomarker. We and others have shown that synthetic high affinity integrin ligands can be used to improving the diagnosis, imaging and drug delivery to lung cancer. The objective of this proposal is to optimize and characterize peptide ligands for targeting integrins in lung cancer. Our project has immediate translational potential in improving drug delivery and clinical assays currently used for molecular and immune biomarkers in lung cancer patients receiving molecularly targeted and/or immune checkpoint inhibitor therapy, a step forward to precision cancer care in lung cancer.

PI_NAMEs: LI, TIANHONG  (contact)

PROJECT_TERMS: Affinity;Antibody Therapy;Antitumor Response;Biological Assay;Biological Markers;Biopsy;Blood;Blood Banks;Blood specimen;Body Fluids;cancer cell;Cancer Etiology;cancer immunotherapy;Cancer Patient;cancer therapy;cancer type;Carcinoma;Case Study;CD8-Positive T-Lymphocytes;Cell Death;Cells;Cessation of life;checkpoint therapy;Clinical;clinical application;clinical decision-making;Clonal Evolution;companion diagnostics;Complex;cost;Detection;detection sensitivity;Diagnosis;Diagnostic;diagnostic platform;Diagnostic tests;Disease;Distant Metastasis;Drug Delivery Systems;Drug resistance;Drug Targeting;drug-sensitive;effective therapy;Epidermal Growth Factor Receptor;Equilibrium;exosome;FDA approved;Flow Cytometry;Fluorescent in Situ Hybridization;General Population;Genes;Genomics;Genotype;Goals;Growth;Guidelines;Hot Spot;Image;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;Immune system;Immunodiagnostics;Immunohistochemistry;Immunologic Markers;Immunotherapy;improved;improved outcome;In Vitro;in-vitro diagnostics;Individual;innovation;Institutional Review Boards;Integrin alpha3beta1;Integrin alpha4beta1;Integrins;Life;Ligands;liquid biopsy;Lymphocyte;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;Malignant Pleural Effusion;Membrane;Meta-Analysis;microvesicles;military veteran;minimally invasive;Modality;Molecular;Molecular Abnormality;molecular diagnostics;molecular marker;Molecular Target;molecular targeted therapies;Monitor;multiplex assay;Mutation;National Comprehensive Cancer Network;Neoplasm Circulating Cells;neoplastic cell;new technology;next generation sequencing;Non-Small-Cell Lung Carcinoma;novel;novel diagnostics;novel therapeutic intervention;Oncogenes;Operative Surgical Procedures;Patient Care;patient population;Patients;Peptides;peripheral blood;personalized medicine;Phase;Plasma;Pleural effusion disorder;Polymerase Chain Reaction;precision medicine;precision oncology;Process;programmed cell death ligand 1;programmed cell death protein 1;Proteins;Protocols documentation;Recommendation;resistance mutation;Resources;response;Sampling;Selection for Treatments;Shapes;single cell genomics;specific biomarkers;Specificity;Specimen;success;Surface;T-Cell Receptor;targeted treatment;Testing;Thoracentesis;Time;translational potential;treatment response;tumor;tumor DNA;Tumor Specific Peptide;Tumor-Derived;tumorigenesis;Veterans

PROJECT_TITLE: Targeting Integrins in Lung Cancer


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PI_NAMEs: PATEL, HEMAL H (contact)

PROJECT_TERMS: Biology;Cardiac;Cause of Death;Caveolae;caveolin-3;Caveolins;Cell membrane;Cell Physiology;Cells;Cholesterol;Complex;Coupled;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Data;Diabetes Mellitus;diabetic;diabetic cardiomyopathy;diabetic patient;Dissociation;Electron Transport;Epidemic;Exposure to;fatty acid metabolism;flasks;Functional disorder;Funding;Gene Transfer;Generations;healing;Heart;Heart Diseases;heart function;Homeostasis;Hyperglycemia;Hyperinsulinism;in vivo Model;Injury;insight;Insulin Receptor;insulin signaling;Laboratories;Lipids;Location;Membrane;Metabolic;Metabolism;Microscopic;Mitochondria;Modeling;Molecular;Multiprotein Complexes;Myocardial dysfunction;Myocardial Ischemia;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;Organ;Organelles;overexpression;Pathology;Persons;Phosphotransferases;pre-clinical;Process;Proteins;receptor;Receptor Signaling;Regulation;repaired;Reperfusion Injury;response;Role;scaffold;Signal Transduction;Signaling Molecule;Site;SLC2A1 gene;Sphingolipids;Stress;Structural Protein;Structure;System;Testing;Therapeutic

PROJECT_TITLE: Molecular Regulators of Mitochondria in Diabetic Cardiomyopathy


NIH_SPENDING_CATS: Biotechnology;Cancer;Gene Therapy;Genetics;Hematology;Lymphatic Research;Lymphoma;Orphan Drug;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

ORG_STATE: MA

PHR: Project Narrative Diffuse large B-cell lymphoma patients are resistant to current standard of care therapies, including RCHOP, and their tumors over-express an oncogenic microRNA, miR-155. In this proposal, we will develop next generation chemically modified and highly active antisense peptide nucleic acids (PNAs) for potent inhibition of miR-155 in mouse models of lymphoma, both genetically engineered and patient-derived. The proposal is built on the collaborative work of a team of experienced investigators with complementary expertise in pH-dependent peptide delivery to tumors, PNA design and synthesis, and mouse models of microRNA-driven malignancies, with the goal of developing this novel class of highly targeted anti-neoplastic agents for further clinical development.

PI_NAMEs: SLACK, FRANK J. (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: addiction;Adopted;Affinity;alpha helix;Amino Acids;Amyloidosis;Animals;Antineoplastic Agents;Antisense Oligonucleotide Therapy;Apoptosis;B-Lymphocytes;Binding;biophysical properties;Cancer Model;cancer therapy;cancer type;Cell Culture Techniques;Cell Line;Cessation of life;Chemicals;chemotherapy;clinical development;Clinical Trials;Cutaneous T-cell lymphoma;Data;design;Development;Diffuse Large-Cell Lymphoma;Drug Kinetics;Drug Targeting;Effectiveness;experience;Future;Gelshift Analysis;Genetic Engineering;Glycine;Goals;Hematopoietic Neoplasms;Human;human model;hypolipidemia;improved;In Vitro;in vivo;Incidence;Investigation;Laboratories;large cell Diffuse non-Hodgkin's lymphoma;leukemia/lymphoma;Lipid Bilayers;Lipids;Lymphoma;Lymphoma cell;Malignant Neoplasms;Mediating;Messenger RNA;Methods;MicroRNAs;Modeling;Molecular Conformation;Molecular Target;mouse model;multidisciplinary;Mus;Nature;neoplastic cell;next generation;novel;nuclease;nucleic acid analog;Nucleic Acid Conformation;Nucleic Acids;oncogene addiction;Oncogenic;overexpression;patient derived xenograft model;Patients;Peptide Hydrolases;Peptide Nucleic Acids;Peptides;Pharmaceutical Preparations;phosphodiester;Polyneuropathy;Prealbumin;precision drugs;Property;Publishing;Quality Control;Research Personnel;Resistance;RNA Interference;Series;Small Interfering RNA;Solubility;Specificity;Spinal Muscular Atrophy;standard of care;synthetic construct;T-Cell Lymphoma;targeted cancer therapy;Technology;Testing;Therapeutic;therapeutic miRNA;Tissues;Toxic effect;Transgenic Mice;Translating;Transplantation;tumor;tumor microenvironment;Untranslated RNA;Vertebral column;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Targeting microRNAs in the tumor microenvironment with pHLIP conjugated next generation chemically modified PNAs

STUDY_SECTION: GDD

STUDY_SECTION_NAME: Gene and Drug Delivery Systems Study Section[GDD]


ORG_CITY: LOS ANGELES

ORG_NAME: VA GREATER LOS ANGELES HEALTHCARE SYSTEM

PHR: Inflammatory bowel diseases (IBD) affect Veterans at a disproportionate rate. IBD results from a complex interaction among the patient’s intestinal tract, gut microbiota and environmental factors such as diet. Pomegranate extract (PomX) and its gut microbiome metabolite urolithin A (UA) decreased the abundance of pathogens associated with IBD and reduced intestinal inflammation. Individual’s capability of producing UA depends on his/her gut microbiota. Furthermore, the capability is linked with chronic disease risks that may determines individual response to diet intervention. Therefore, we are proposing to evaluate the efficacy of PomX in reducing IBD symptoms in mice with and without UA producing capability separately. Results from our studies will be a premise for future clinical studies to explore the use of dietary PomX/UA supplements as alternative and adjuvant therapy based on individual gut microbiome status to improve gut mucosa inflammation in IBD, thus reduce the use of immune-suppressing medications in patients with mild to moderately active IBD.

PI_NAMEs: LI, ZHAOPING  (contact)

PROJECT_TERMS: Adjuvant Therapy;Affect;Alternative Therapies;Anti-Inflammatory Agents;Antiinflammatory Effect;Attenuated;Bacteria;Blood;CD4 Positive T Lymphocytes;Cell Line;Cell Separation;Cells;chemically induced colitis;Chemicals;Chronic;Chronic Disease;Clinical;Clinical Research;Clinical Trials;Colitis;Colon;Complex;Crohn's disease;cytokine;Data;Development;Diagnosis;Diet;dietary;Dietary Factors;Dietary Intervention;Dietary Supplementation;dietary supplements;Disease Progression;disorder risk;efficacy evaluation;Ellagi-Tannins;Ellagic Acid;Environmental Risk Factor;Epithelium;Fatty acid glycerol esters;Flare;Food;Future;Gnotobiotic;gut bacteria;gut inflammation;gut microbiome;gut microbiota;Gut Mucosa;Health;Human Microbiome;Immune;Immune response;Immune system;Immunity;improved;In Vitro;Individual;individual response;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Infiltrate;Intake;inter-individual variation;Interleukin-10;Intervention;Intestinal Mucosa;Intestines;intraperitoneal;Knock-out;Knockout Mice;Link;Mediating;Mesentery;Metabolic;metabolic phenotype;metabolomics;metagenomic sequencing;microbial;microbiome;microbiome alteration;microbiota;Modeling;Molecular;mouse model;Mucositis;Mucous Membrane;murine colitis;Mus;Nature;NF-kappa B;novel;novel strategies;Nutrient;pathobiont;pathogen;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Play;Pomegranate;preclinical study;Predisposition;Prevalence;prevent;Production;Protocols documentation;Rag1 Mouse;Recommendation;Relapse;Research;Resistance;response;Role;Shapes;Shotguns;Signal Transduction;single nucleus RNA-sequencing;Spontaneous colitis;Sucrose;Supplementation;symptomatic improvement;Symptoms;T cell response;T-Lymphocyte;Therapeutic;Tight Junctions;Tissues;Transplantation;treatment response;Ulcerative Colitis;Variant;Veterans;Wild Type Mouse

PROJECT_TITLE: Pomegranate Extract and Its Microbial Metabolite Urolithin A Suppress IBD through Modulation of the Gut Microbiome and T Cell Inflammatory Immune Responses


NIH_SPENDING_CATS: Digestive Diseases;Liver Disease;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: Project Narrative To function normally, cells must coordinate fat or lipid metabolism and much of this coordinating occurs in an organelle called the endoplasmic reticulum. We recently discovered the biochemical reaction of an enzyme in this cell compartment called FIT2, which is required for health of cells or metabolic tissues, such as the liver. The projects of this proposal are aimed at understanding how this enzyme works to coordinate cellular lipid metabolism, how cells and tissues malfunction when the enzyme is deficient, and how reduced levels of this enzyme relates to metabolic disease and cancer metabolism.

PI_NAMEs: FARESE, ROBERT V (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Acyl Coenzyme A;Adipose tissue;Affect;Apoptosis;Binding;Biochemical;Biochemical Reaction;Biochemistry;biological adaptation to stress;biological systems;Biology;Catabolism;Cell Compartmentation;Cell Physiology;Cells;Chronic;Cytoprotection;Data;Defect;Diglycerides;Disease;Endoplasmic Reticulum;endoplasmic reticulum stress;Enzymes;Equilibrium;Exhibits;Face;Family;Fatty Acids;Fatty Liver;gene synthesis;Genes;Health;Hepatocyte;Homeostasis;Human;human disease;In Vitro;interdisciplinary approach;Investigation;Knowledge;Link;lipid metabolism;Lipids;Liver;Liver diseases;liver injury;Location;Malignant neoplasm of liver;Malignant Neoplasms;Mammalian Cell;Measures;Mediating;Membrane;Membrane Fluidity;membrane synthesis;Metabolic;Metabolic Diseases;Mohr-Tranebjaerg syndrome;Molecular;mouse model;Multiple Myeloma;Mus;Muscle;Obesity;Organelles;Pathogenesis;Pathway interactions;Phenotype;Physiological;PPAR alpha;Primary carcinoma of the liver cells;Process;protective pathway;Protein Secretion;Proteins;Research;response;Role;sensor;structural biology;System;Therapeutic;Tissues;Transmembrane Domain;tumor metabolism;Work;Yeasts

PROJECT_TITLE: Lipotoxic Protective Response of the Endoplasmic Reticulum

STUDY_SECTION: MBPP

STUDY_SECTION_NAME: Membrane Biology and Protein Processing Study Section[MBPP]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: GAINESVILLE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: PROJECT NARRATIVE Isoform switch occurs frequently in cancer, and in this application we will investigate the oncogenic role of Tet1 alternative isoform in the development of Myelodysplastic Syndrome (MDS), a hematological malignant disease. In addition, we will determine the molecular mechanisms that mediate the function of Tet1 isoform in hematopoietic stem progenitor cells (HSPCs). Our work will provide new insights into the distinct role of TET1 isoform upregulation in the pathogenesis of MDS as well as its specific role in maintaining epigenetic landscapes and gene regulation in HSPCs

PI_NAMEs: QIAN, ZHIJIAN  (contact)

PROGRAM_OFFICER_NAME: DI FRONZO, NANCY L

PROJECT_TERMS: Acute Erythroblastic Leukemia;acute lymphoblastic leukemia cell;Acute T Cell Leukemia;Affect;Anemia;APC gene;ATAC-seq;B-Cell Lymphomas;beta catenin;Binding;Bone Marrow Cells;Catalytic Domain;CD34 gene;Cells;ChIP-seq;Chromatin;demethylation;Development;Diagnosis;Disease;Distal;DNA;DNA Methylation;Down-Regulation;Dysmyelopoietic Syndromes;Ectopic Expression;Enhancers;Epigenetic Process;Erythroblasts;erythroid differentiation;Erythroid Progenitor Cells;Erythropoiesis;EVI1 gene;Gene Expression;Gene Expression Regulation;Genes;Genomic approach;Hematology;Hematopoiesis;hematopoietic stem cell self-renewal;Hematopoietic stem cells;Hematopoietic System;Hemin;Human;In Vitro;in vivo;Individual;Ineffective Hematopoiesis;insight;K562 Cells;knock-down;leukemia;Maintenance;Malignant - descriptor;Malignant Neoplasms;Mediating;Molecular;mouse model;Mus;Myelogenous;Myeloid Leukemia;N-terminal;Normal tissue morphology;Nucleic Acid Regulatory Sequences;Oncogenes;Oncogenic;overexpression;Pathogenesis;Pathway interactions;Patients;Pattern;Play;Proliferating;promoter;Protein Family;Protein Isoforms;Regulatory Element;Role;stem cell differentiation;stem cell function;Stretching;Testing;Transcriptional Regulation;transcriptome;transcriptome sequencing;transgene expression;Transgenic Mice;tumor;Tumor Suppressor Genes;Tumor Suppressor Proteins;Up-Regulation;WNT Signaling Pathway;Work;Xenograft procedure

PROJECT_TITLE: Role of the TET1 short isoform in MDS development and maintenance

STUDY_SECTION: BBHV

STUDY_SECTION_NAME: Basic Biology of Blood, Heart and Vasculature Study Section [BBHV]


ADMINISTERING_IC: AA

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Pediatric;Prevention;Screening and Brief Intervention for Substance Misuse;Social Determinants of Health;Substance Misuse;Underage Drinking

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF MEMPHIS

PHR: Emerging adults (ages 18-25) consume alcohol at higher rates than any other age group. The social and health consequences of alcohol misuse are greatest among emerging adults who are not college students or graduates of four-year colleges, many of whom also experience poverty, elevated stress, and a lack of behavioral alternatives to alcohol use. We will evaluate a promising intervention approach for non-student emerging adults that attempts to reduce alcohol use by decreasing stress and increasing engagement in positive and goal-directed activities that provide meaningful alternatives to alcohol use.

PI_NAMEs: MURPHY, JAMES G. (contact)

PROGRAM_OFFICER_NAME: KWAKO, LAURA ELIZABETH

PROJECT_TERMS: active method;Address;Affective Symptoms;African American;Age;age group;Alcohol abuse;alcohol consequences;Alcohol consumption;alcohol demand;alcohol measurement;alcohol misuse;alcohol related consequences;alcohol related problem;alcohol use disorder;Arousal;behavior change;Behavioral;behavioral economics;Behavioral Mechanisms;Belief;Black race;brief alcohol intervention;chronic alcohol ingestion;Clinical Research;college;Communities;community center;comorbidity;Coping Skills;cost effective;COVID-19 pandemic effects;depressive symptoms;Development;discounting;Disparity;dissemination research;dissemination trial;drinking;Drug usage;economic impact;Education;Educational Intervention;efficacy evaluation;Elements;emerging adult;Ethnic Population;Evaluation;experience;Feedback;follow-up;Future;Goals;Health;Healthcare;Heavy Drinking;heavy drinking college student;help-seeking behavior;high risk;Income;Informal Social Control;Institute of Medicine (U.S.);Intervention;Laboratory Research;marginalization;Marketing;Measures;Mediating;member;Mental Depression;Mental Health;Modality;Moods;National Institute on Alcohol Abuse and Alcoholism;negative affect;novel;Outcome;Participant;Physiological;Population;post intervention;Poverty;preference;Preventive care;psychiatric comorbidity;Psychological reinforcement;Race;racial population;Randomized;randomized, clinical trials;reduced alcohol use;reduced substance use;Relaxation Therapy;Reporting;Research;Rewards;Risk;Risk Factors;secondary outcome;sex;Site;social;Stress;Stress and Coping;stress management;stress reduction;Suggestion;Symptoms;telehealth;Testing;tool;treatment response;university student;Woman;Workplace

PROJECT_TITLE: Behavioral economic and wellness-based approaches for reducing alcohol use and consequences among diverse non-student emerging adults


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cardiovascular;Clinical Research;Dementia;Heart Disease;Neurodegenerative;Neurosciences

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

PHR: Narrative The purpose of this application is to investigate the role of complement, circulating red blood cells (RBCs), and red cell-derived extracellular vesicles (EVs) in pathogenesis of Alzheimer’s disease and the crosstalk between the central nervous system and the peripheral tissue. We will use in-vitro and in-vivo assays, human tissue samples and a mouse animal model to test our hypothesis.

PI_NAMEs: DEL MONTE, FEDERICA  (contact);GHIRAN, IONITA CALIN

PROGRAM_OFFICER_NAME: YABE, IDALIA MONTANO

PROJECT_TERMS: Abeta clearance;Adsorption;Affect;Age;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease patient;Amyloid;Amyloid beta-42;Amyloid beta-Protein;Animal Model;Binding;Biological Assay;Biological Markers;Blood;Brain;Brain region;Buffers;Cardiac Myocytes;Cardiomyopathies;Cell Communication;Cell membrane;Cell surface;Cells;Central Nervous System;Complement;Complement 1q;Complement 3b;Complement 4b;Complement Activation;Complement Receptor;complement system;Cytosol;Data;Defect;Dementia;Deposition;Disease;Disease Progression;Distal;Drug or chemical Tissue Distribution;Ensure;Environment;Erythrocytes;exosome;extracellular vesicles;Fluorescence;Functional disorder;Future;Gender;Genetic Polymorphism;genome wide association study;Heart;Heart failure;heart function;Human;human tissue;immune clearance;In Vitro;in vivo;Individual;Kupffer Cells;Late Onset Alzheimer Disease;Left;Ligands;Ligation;Light;Link;Liver;Mediating;Microglia;mouse model;Mus;Myocardial tissue;neuron loss;Neuronal Dysfunction;Neurons;Organ;particle;Pathogenesis;Pathway interactions;Patients;Peripheral;Plasma;Predisposition;prevent;Process;Proteins;Proxy;Quality of life;Reporting;Risk;Role;Senile Plaques;Structure;System;Testing;Therapeutic;Tissue Sample;Tissues;Transfusion;Validation

PROJECT_TITLE: Red Blood Cells shuttle beta amyloid between brain and heart: implications for the pathogenesis and the progression of Alzheimer's and Cardiomyopathy

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Cancer;Cancer Genomics;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Human Genome;Liver Cancer;Liver Disease;Rare Diseases;Substance Misuse

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative Alcoholic liver disease (ALD) is a primary cause of chronic liver diseases in western nations. Our current proposal focuses on our new discovery that a paracrine signaling between acetylcholine-producing immune cells in the liver and CHRNA2 expressed in hepatocytes, plays an adaptive/protective role in the context of ALD. Insights gained from proposed studies may lead to new therapeutic targets counteracting human liver diseases caused by chronic excessive alcohol consumption.

PI_NAMEs: WU, JUN  (contact)

PROGRAM_OFFICER_NAME: MURRAY, GARY

PROJECT_TERMS: Acetaldehyde;Acetylcholine;Agonist;Alcohol consumption;Alcohol dehydrogenase;alcohol exposure;Alcoholic Hepatitis;Alcoholic liver damage;Alcoholic Liver Diseases;Alcohols;Biogenesis;Cell Line;Cell membrane;Cell Separation;Cells;Choline O-Acetyltransferase;cholinergic;Chronic;chronic alcohol ingestion;Chronic Hepatitis;chronic liver disease;Cirrhosis;Collaborations;Country;Data;Development;Diet;dietary control;Diffusion;dysbiosis;effective therapy;endoplasmic reticulum stress;Enzymes;Ethanol;experimental study;Fatty Liver;Fibrosis;Flow Cytometry;Gender;Gene Deletion;Genetic;Heavy Drinking;Hematopoietic;Hepatic;Hepatocyte;HepG2;Human;Immune;Impairment;In Vitro;in vivo;Inflammation;Inflammatory;Injury;insight;interdisciplinary approach;Intestines;Investigation;Ion Channel;Ion Channel Gating;Knockout Mice;Kupffer Cells;Ligands;lipid biosynthesis;Liver;Liver Cirrhosis;Liver diseases;Liver Fibrosis;liver function;liver injury;liver preservation;liver transplantation;loss of function;Macrophage;Mediating;Modeling;Molecular;monocyte;mortality;mouse model;Mus;new therapeutic target;Nicotinic Receptors;novel;Paracrine Communication;pathogen;Pathogenesis;Pathway interactions;Pattern;Play;Primary carcinoma of the liver cells;recruit;Regimen;Regulation;Regulatory Pathway;Reporter;Reporting;Risk;Role;Route;Sampling;screening;Series;sexual dimorphism;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Site;small molecule;Spatial Distribution;Symptoms;Testing;Therapeutic Intervention;Therapeutic Uses;three-dimensional visualization;Tissues;transcriptome;transcriptomics;Visualization;Woman

PROJECT_TITLE: A novel cholinergic circuitry in alcoholic liver disease (NIAAA)

STUDY_SECTION: XNDA

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


ADMINISTERING_IC: NR

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

PHR: PROJECT NARRATIVE Heart failure, the fastest growing cardiovascular condition in the United States, is associated with significant symptom burden. The results of this study will shed light on our understanding of the role of biological and physiological mechanisms in explaining heart failure symptoms, particularly groups of co-occurring symptoms, over time. The knowledge generated from this study will be used to develop personalized symptom management interventions for adults with heart failure.

PI_NAMEs: DENFELD, QUIN ELEANOR (contact)

PROGRAM_OFFICER_NAME: GIVENS-BRADLEY, SHANNON SHAREE

PROJECT_TERMS: Acute;Address;Adult;Affective Symptoms;Age;Anxiety;associated symptom;Biological;Biological Markers;biomarker panel;Body Weight decreased;Cardiovascular system;Categories;Chronic;Clinical;cognitive function;Congestive Heart Failure;Coupled;Dyspnea;EFRAC;Elderly;endothelial dysfunction;Event;exhaustion;Failure;Fibrosis;frailty;Functional disorder;Gender;Growth;Heart failure;hemodynamics;Heterogeneity;hospital readmission;Hospitalization;Hospitals;Impairment;improved;individualized medicine;infancy;Inflammation;innovation;Insulin Resistance;Intervention;Knowledge;Longitudinal Studies;Malignant Neoplasms;Measures;Mediating;Mediation;Mental Depression;Methods;Modeling;Myocardial;Nature;Outcome;Pain;Patient Outcomes Assessments;Patients;Phase;Phenotype;Physical activity;physical symptom;Physiological;Process;programs;Pump;Quality of life;reduce symptoms;Research;Risk;Role;Skeletal Muscle;Sleep;Stress;Symptom Burden;symptom cluster;symptom management;symptom science;symptomatic improvement;Symptoms;therapy development;Time;time use;United States

PROJECT_TITLE: Biological and Physiological Mechanisms of Symptom Clusters in Heart Failure (BIOMES-HF)

STUDY_SECTION: NRCS

STUDY_SECTION_NAME: Nursing and Related Clinical Sciences Study Section[NRCS]


ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA CITY VA MEDICAL CENTER

ORG_STATE: OK

PHR: Project Narrative Two-thirds of all veterans are 55 years of age or older. Sarcopenia is a syndrome that effects approximately 25% of the U.S. population over the age of 70 characterized by progressive loss of skeletal muscle mass and strength with an increased risk of adverse outcomes such as physical disability, poor quality of life and even death. Loss of motor neuron innervation to the muscle (denervation) is a major contributor to sarcopenia. Our data shows that lipid hydroperoxide generation is significantly greater in denervated muscle and aged muscle when compared to sham or young controls, respectively. When we reduce lipid hydroperoxides or slow the generation of lipid hydroperoxides in denervated muscle we can slow muscle mass loss. In this proposal, we will define potential mechanisms by which lipid hydroperoxides trigger sarcopenia, and identify therapeutic targets to treat sarcopenia in veterans.

PI_NAMEs: BROWN, JACOB LEVI (contact)

PROJECT_TERMS: Acceleration;adverse outcome;Age;Age Months;age related;Age Years;age-related muscle loss;Aging;Animal Genetics;Animal Model;Arachidonate 15-Lipoxygenase;Arachidonic Acids;Atrophic;Attenuated;Body Composition;catalase;Cessation of life;Communication;Cytoplasm;Data;Denervation;design;Development;Diabetes Mellitus;effective intervention;effective therapy;Eicosanoids;Electron Transport;Enzymes;experimental study;falls;Fiber;Fracture;Functional disorder;gene therapy;Generations;Genetic;Genetic Induction;glutathione peroxidase;Goals;Hand Strength;Health;Health Expenditures;healthspan;Hindlimb;Hydrogen Peroxide;improved;Intervention;Knockout Mice;Lipid Peroxidation;Lipid Peroxides;Lipids;Maintenance;Malnutrition;Measures;Mediator;meetings;Membrane;Mental Depression;Mentors;Mitochondria;mitochondrial dysfunction;Modeling;Morphology;Motor Neurons;mouse model;Movement;Mus;Muscle;muscle aging;muscle degeneration;Muscle Fibers;muscle form;Muscle function;Muscle Proteins;muscle strength;Muscular Atrophy;nerve supply;Neuromuscular Junction;novel;old mice;overexpression;oxidation;Oxidative Stress;Patients;Permeability;pharmacologic;Phospholipase A2;Phospholipids;physically handicapped;Population;Prevalence;Production;protein biomarkers;Protein Biosynthesis;protein degradation;Proteins;Psyche structure;Quality of life;reduced muscle mass;Research Technics;response;Risk;Running;sarcopenia;Scientist;Secondary to;Skeletal Muscle;skeletal muscle wasting;stable isotope;Structure;Superoxides;symposium;Syndrome;Testing;therapeutic target;therapy design;Training;Veterans

PROJECT_TITLE: Lipid hydroperoxides in sarcopenia and muscle wasting: mechanisms and intervention


ORG_CITY: OMAHA

ORG_NAME: OMAHA VA  MEDICAL CENTER

ORG_STATE: NE

PHR: Dysregulation of sex steroid synthesis and secretion is a leading cause of infertility in both male and females. Infertility affects 1 in every 6 couples, with male infertility playing a primary factor in a third of all cases. Moreover, infertility affects about 10 percent of the female population (6.1 million) in the United States; about 100,000 female Veterans of reproductive age. Considering the number of men and women who suffer from infertility and secondary affects associated with dysregulation of sex steroid biogenesis understanding mechanisms that regulate PKA signaling and mobilization of substrate for steroid production hold great potential to positively impact reproductive health and overall quality of life. This research proposal centers on the identification of the molecular mechanisms responsible for transmitting signals from the outside environment to the mitochondria, initiating changes in mitochondrial structure and function, and then translating molecular responses into changes in steroid biosynthesis.

PI_NAMEs: PLEWES, MICHELE R (contact)

PROJECT_TERMS: A kinase anchoring protein;Adenylate Cyclase;Adipocytes;Adrenal Glands;Affect;Age;Anabolism;Attenuated;Binding;Biogenesis;Biology;C-terminal;career;Cells;Cholesterol;Collaborations;Communication;Complex;Coupled;Couples;Crista ampullaris;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Data;design;Docking;Doctor of Philosophy;Dynamin;early pregnancy loss;Embryonic Development;Endocrinologist;Endocrinology;Environment;Enzymes;Erectile dysfunction;Feedback;Female;female reproductive system;Funding;Goals;Gonadal Steroid Hormones;GTP-Binding Proteins;Guanosine Triphosphate Phosphohydrolases;Headache;Healthcare Systems;Hormone Responsive;implantation;Infertility;Inner mitochondrial membrane;Iowa;knock-down;LH Receptors;Lipids;Luteinizing Hormone;male;Male Genital Organs;Male Infertility;Mammals;Measures;Mediating;Medical center;Membrane;men;Mentors;Mentorship;Metabolic;Metalloproteases;Migraine;Mitochondria;Mitochondrial Proteins;Modeling;Molecular;Morphology;Nebraska;novel;OPA1 gene;Organelles;Outer Mitochondrial Membrane;Ovarian;Ovary;Phosphorylation;Pituitary Hormones;Play;Population;Positioning Attribute;post-doctoral training;Postdoctoral Fellow;Pregnancy;Production;Progesterone;protein activation;Protein Isoforms;protein protein interaction;Proteins;Quality Control;Quality of life;receptor;Regulation;reproductive;Reproductive Health;Research;Research Personnel;Research Proposals;Research Support;response;Role;Scientist;Series;Sexual Dysfunction and Infertility;Shapes;Signal Induction;Signal Transduction;Site;Steroid biosynthesis;Steroids;Structure;System;Tertiary Protein Structure;Testing;Testis;Testosterone;testosterone biosynthesis;Time;Tissues;Translating;Transmembrane Domain;transmission process;United States;Universities;Uterus;Veterans;Woman;Work;Zinc

PROJECT_TITLE: Mitochondrial Dynamics and Steroidogenesis


ORG_CITY: St. Louis

ORG_NAME: ST. LOUIS VA MEDICAL CENTER

ORG_STATE: MO

PHR: Project Narrative Numerous veterans suffer from advanced heart failure, a condition for which cardiac transplantation remains a preferred therapy. Outcomes after heart transplantation are severely limited by primary graft dysfunction, an inflammatory condition that occurs early after transplantation and is attributable to ischemia reperfusion injury. Primary graft dysfunction is characterized by infiltration of innate immune cells, such as neutrophils and monocytes into the transplanted heart. Our laboratory has developed intravital imaging approaches that has allowed us to define cellular and molecular requirements for leukocyte trafficking into cardiac grafts. In this grant, we propose to study how donor cell populations and signaling pathways regulate the recruitment of immune cells to hearts after transplantation. Targeting these pathways will provide novel avenues to ameliorate primary graft dysfunction and improve outcomes after heart transplantation.

PI_NAMEs: KREISEL, DANIEL  (contact)

PROJECT_TERMS: adaptive immune response;Adhesions;Automobile Driving;Cardiovascular Diseases;CCL2 gene;CCL7 gene;Cell Death;Cells;Cessation of life;chemokine;Chest;Complex;Cues;CXCL5 gene;Data;effective therapy;Endothelial Cells;Endothelium;extracellular;Extravasation;Foundations;Funding;graft dysfunction;Graft Rejection;Grant;Health;Heart;Heart failure;Heart Transplantation;Human;Image;imaging approach;imaging platform;Immune;Immune response;Immune Targeting;improved outcome;Infiltration;Inflammation;Inflammatory;Inflammatory Response;Interferon Type I;intravital imaging;Iron;isoimmunity;Laboratories;Leucocytic infiltrate;Leukocyte Trafficking;Leukocytes;Macrophage;Mediating;migration;military veteran;Molecular;monocyte;Mus;Myeloid Cells;Myocardial Ischemia;Myocardial Reperfusion Injury;neutrophil;Neutrophil Infiltration;novel;novel therapeutics;Outcome;Pathway interactions;Patients;Pattern;pharmacologic;Plasma Cells;Play;Population;Positron-Emission Tomography;Process;Production;receptor;recruit;Reperfusion Injury;Reperfusion Therapy;Reporting;response;RNA;Role;Shapes;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Site;Specific qualifier value;Structure of left gastric vein;Surface;T-Lymphocyte;Techniques;Testing;Time;Tissues;TLR3 gene;TLR4 gene;trafficking;Transplant Recipients;Transplantation;two photon microscopy;Veterans;Visualization

PROJECT_TITLE: Leukocyte trafficking in thoracic grafts