NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Hematology;Immunotherapy;Lymphatic Research;Lymphoma;Rare Diseases

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: Project Narrative Our goal is to develop novel strategies to prevent toxicities, enhance efficacy, and modulate the microenvironment after chimeric antigen receptor T (CART) cell therapy for the treatment of cancer. We have identified GM-CSF and as a key cytokine in mediating CART cell toxicity and impairing their functions. We are planning to study these interactions in lab experiments, preclinical models, and in a first-in-human clinical trial of GM-CSF neutralization with CART cell therapy to prevent neurotoxicity.

PI_NAMEs: KENDERIAN, SAAD J. (contact)

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Acute Lymphocytic Leukemia;Affect;Apoptosis;Apoptotic;B lymphoid malignancy;B-Cell Lymphomas;Blood specimen;cancer therapy;CAR T cell therapy;CD19 gene;cell behavior;Cell Death Induction;Cell Physiology;Cell Therapy;Cells;chimeric antigen receptor;Clinical;Clinical Trials;cohort;Collaborations;COVID-19;COVID-19 patient;cytokine;cytokine release syndrome;Data;Development;Etiology;first-in-human;Functional disorder;Funding;Goals;Granulocyte-Macrophage Colony-Stimulating Factor;Granulocyte-Macrophage Colony-Stimulating Factor Receptors;Hematopoietic;Impairment;improved;In Vitro;in vivo;insight;Interleukin 6 Receptor;Interruption;Knock-out;Laboratories;laboratory experiment;large cell Diffuse non-Hodgkin's lymphoma;Life;Mediating;Mediator;monocyte;monocyte colony stimulating factor;Multi-Institutional Clinical Trial;Multicenter Studies;Myelogenous;Myeloid Cells;neurotoxicity;neutralizing antibody;novel;novel strategies;Outcome;Outpatients;Pathway interactions;Patients;Phase;Phase I/II Clinical Trial;post-COVID-19;pre-clinical;Pre-Clinical Model;prevent;Prevention;Publishing;receptor;Receptor Cell;Refractory;Relapse;Resistance;Resolution;response;Role;Sampling;severe COVID-19;Severities;Site;T-Lymphocyte;Testing;Therapeutic;tocilizumab;tool;Toxic effect;transcription activator-like effector nucleases;tumor;United States;Work;Xenograft Model

PROJECT_TITLE: Towards Safer and More Effective CART Cell Therapy Through the Modulation of Myeloid Cytokines

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


ADMINISTERING_IC: TW

ARRA_FUNDED: N

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Behavioral and Social Science;HIV/AIDS;Social Determinants of Health

ORG_CITY: KAMPALA

ORG_COUNTRY: UGANDA

ORG_FIPS: UG

ORG_NAME: MAKERERE UNIVERSITY COLLEGE OF HEALTH SCIENCES

PHR: NARRATIVE The proposed program will develop a sustainable, model master’s degree program in international research ethics based at a strengthened Bioethics Center at Makerere University to produce graduates with potential to become bioethics leaders. Bioethics will become a significant part of their career participating in education of the next generation of bioethicists, design and implementation of high-quality ethical health research, conduct bioethics research, and provide expert advice to researchers, and policy makers. The success of this program will translate into improvements in ethical decision making for research leading to enhancements in responsible conduct of research, and overall protection of research participants.

PI_NAMEs: SEWANKAMBO, NELSON K (contact)

PROGRAM_OFFICER_NAME: SINA, BARBARA J

PROJECT_TERMS: Acceleration;Achievement;Address;Admission activity;Advisory Committees;Africa;Africa South of the Sahara;African;Applied Research;Attention;Award;behavioral health;Bioethics;Bioethics Consultants;career;Clinical;Collaborations;college;Consultations;cost;Country;Decision Making;Degree program;design;Development;Doctor of Philosophy;Education;Educational Activities;Educational Curriculum;Educational Status;Empirical Research;Ensure;Environment;Ethical Issues;Ethics;experience;Faculty;flexibility;Foundations;Funding;global health;Goals;Grant;Growth;Guidelines;Health;Health Sciences;improved;Indigenous;Industry;innovation;Institution;Institutionalization;International;Journals;Knowledge;Leadership;leadership development;life-long learning;low and middle-income countries;Master of Science;Mentors;Mentorship;Modeling;Nature;Nerve;next generation;Occupations;Participant;Peer Review;Policies;Policy Developments;Policy Maker;Postdoctoral Fellow;Process;programs;public health research;Publishing;Research;Research Ethics;Research Personnel;Research Project Grants;Resource-limited setting;Resources;responsible research conduct;service delivery;Service provision;Services;skills;social;social culture;socioeconomic development;Students;success;Training;Training and Education;Training Programs;Translating;Uganda;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: SUSTAIN: Advancing Makerere University Masters of Health Sciences in Bioethics


ADMINISTERING_IC: VA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: Veterans Affairs

ORG_CITY: DETROIT

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: JOHN D DINGELL VA MEDICAL CENTER

ORG_STATE: MI

PHR: There is a high incidence of neurological, respiratory, sleep disturbances and other negative sequelae that persist for many weeks after recovery from an acute COVID-19 infection. These may occur even after a mild infection and can be debilitating for the Veteran who may not be able to return to full function after the infection. One such adverse effect is cognitive dysfunction which is a common component of the post-COVID symptom complex. Our goal is to understand whether sleep disturbances or untreated sleep apnea contribute to the cognitive deficits after COVID-19 infection. Our long-term goal is to advance the rehabilitative health care of Veterans suffering from cognitive impairment by studying the delayed effects and impairments related to COVID infection and develop treatment pathways that will improve the overall health and quality of life of Veterans suffering from these delayed complications.

PI_NAMEs: CHOWDHURI, SUSMITA  (contact)

PROJECT_TERMS: Acute;acute COVID-19;acute infection;Adverse effects;Alleles;Alzheimer's disease patient;Apolipoprotein E;Area;Blood Coagulation Disorders;brain fog;Chronic;Chronic disability;Clinical;Cognitive;Cognitive deficits;cognitive function;Complex;Coughing;COVID-19;COVID-19 cytokine storm;COVID-19 impact;COVID-19 neurocognitive sequelae;COVID-19 pandemic;COVID-19 severity;COVID-19 survivors;cytokine;Data;Development;Diagnostic;Disease;Dyspnea;Encephalopathies;Fatigue;Functional disorder;Future;Genes;Goals;Headache;Health;Healthcare;Hour;Hypoxia;Impaired cognition;Impairment;improved;Incidence;Infection;Inflammation;inflammatory marker;Interleukin-6;Knowledge;Link;Long COVID;long term consequences of COVID-19;Memory impairment;Mental Health;Neurocognitive;Neurocognitive Deficit;Neurologic;Neutrophilia;novel;Observational Study;Obstructive Sleep Apnea;Pathway interactions;Patients;physical conditioning;physical symptom;Pilot Projects;poor sleep;post COVID-19 complications;post SARS-CoV-2 infection;Post-Acute Sequelae of SARS-CoV-2 Infection;post-COVID-19;prospective;Quality of life;Recovery;Recovery of Function;Rehabilitation therapy;Reporting;Research;research study;respiratory;Respiratory Signs and Symptoms;response;Risk;SARS-CoV-2 infection;severe COVID-19;Severities;Sleep;Sleep Apnea Syndromes;Sleep Deprivation;Sleep disturbances;Sleep Fragmentations;sleep quality;Symptoms;Testing;Therapeutic;therapeutic target;TNF gene;trait;Veterans;Virus;Visit

PROJECT_TITLE: Predictors of Post-COVID Clinical and Cognitive Consequences

STUDY_SECTION: RRDS

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


ADMINISTERING_IC: DA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Cannabinoid Research;Chronic Pain;Drug Abuse (NIDA only);Endocannabinoid System Research;Neurosciences;Pain Research;Substance Misuse;Therapeutic Cannabinoid Research

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

ORG_STATE: CA

PI_NAMEs: BOGER, DALE L (contact)

PROGRAM_OFFICER_NAME: LE, HOANG VAN

PROJECT_TERMS: 2-arachidonylglycerol;activity-based protein profiling;Address;Amides;anandamide;Area;Binding Proteins;Blood Vessels;Cannabinoids;Catalepsy;Characteristics;Chronic;chronic pain management;CNR1 gene;CNR2 gene;Constipation;Dependence;desensitization;Development;Disease;Dose;drug discovery;endocannabinoid signaling;Endocannabinoids;endogenous cannabinoid system;Enzymes;Eye;Eye diseases;FAAH inhibitor;fatty acid amide hydrolase;Fatty Acids;Funding Opportunities;Grant;Human Genome;Hydrolysis;in vivo;Inflammation;Inflammatory;inhibitor;innovation;interest;Libraries;lipoprotein lipase;MAGL inhibitor;marijuana use;Medical Marijuana;Monoacylglycerol Lipases;natural hypothermia;neuroprotection;new therapeutic target;Opioid;Pain management;Pharmaceutical Chemistry;Physiological;Proteins;Proteome;PTGS2 gene;receptor;Receptor Signaling;Role;Science;screening;Serine Hydrolase;side effect;Signal Transduction;Signaling Molecule;Site;Therapeutic;therapeutic target;tool;unpublished works;Validation;Vascularization;Ventilatory Depression;Work;Writing

PROJECT_TITLE: Modulating Signaling Endocannabinoids and Fatty Acid Amides

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: DAVIS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative Age, disease, and menopause cause osteoporosis, which predisposes to bone fractures and decreased quality of life. Identifying the mechanisms by which mice acquire striking high bone mass can be used to identify novel therapeutic targets to promote bone anabolism in such diseases.

PI_NAMEs: GENETOS, DAMIAN C;YELLOWLEY-GENETOS, CLARE E (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: Age;Aging;aging population;Anabolism;Attention;Attenuated;beta catenin;bone;bone cell;Bone Growth;bone health;bone loss;bone mass;Cell Physiology;Cell Survival;cell type;cost;Cre driver;Data;dentin matrix protein 1;Development;Disease;Down-Regulation;Estrogens;Fracture;Gene Targeting;Genes;Genetic;Genetic Epistasis;Genetic Transcription;Goals;HIF1A gene;Human;Hypoxia;Hypoxia Inducible Factor;improved;Incidence;Individual;LoxP-flanked allele;Measures;Mediating;Medical;Menopause;Molecular;Motivation;mouse model;Mus;Mutation;new therapeutic target;normoxia;novel;Osteoblasts;Osteocytes;Osteoporosis;osteoporosis with pathological fracture;osteoprogenitor cell;Ovariectomy;Pathway interactions;pharmacologic;Phenotype;prevent;Property;Protein Isoforms;Publishing;Quality of life;receptor;Reporting;Resistance;response;restoration;Rodent;Role;Signal Pathway;Signal Transduction;skeletal;Skeletal Development;Skeleton;socioeconomics;Specificity;Testing;Tumor Suppressor Proteins;ubiquitin-protein ligase;Ubiquitination;Up-Regulation;Wild Type Mouse;WNT Signaling Pathway;Work

PROJECT_TITLE: HIFs in osteocytes

STUDY_SECTION: SBSR

STUDY_SECTION_NAME: Skeletal Biology Structure and Regeneration Study Section[SBSR]


NIH_SPENDING_CATS: Behavioral and Social Science

ORG_CITY: DURBAN

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: UNIVERSITY OF KWAZULU-NATAL

PHR: The South African Research Ethics Training Initiative (SARETI) is the oldest and most established Africa-based Masters program in the field of health research ethics. The new SARETI PhD program equips African research ethics scholars with advanced theoretical, applied and leadership skills to improve health research systems in Africa, improve effectiveness and efficiency of ethics review systems, and maximize the social value of research in Africa through research ethics leadership and scholarship. Intensive on-site training and home-based research work, including attendance of the Johns Hopkins Intensive Global Bioethics Program, will be facilitated by our experienced local and international multidisciplinary faculty.

PI_NAMEs: KRUGER, MARIANA ;WASSENAAR, DOUGLAS R (contact)

PROJECT_TERMS: Achievement;Adult;Africa;African;Area;Bioethics;career development;cohort;Data Analyses;Doctor of Philosophy;Education;Educational workshop;Effectiveness;Ethical Issues;Ethicists;Ethics;experience;Faculty;Funding;Generations;Grant;Health;Home;improved;Institutional Review Boards;interest;International;Lead;Leadership;Mentors;Mentorship;Mission;multidisciplinary;multimodality;Process;programs;Publications;Qualifying;Research;Research Ethics;Research Methodology;Research Proposals;Running;Scholarship;Selection Criteria;Site;skills;Social Values;South African;Structure;Supervision;symposium;System;systems research;Training;United States National Institutes of Health;Universities;Visit;Writing

PROJECT_TITLE: South African Research Ethics Training Initiative (SARETI) Leadership Program


ORG_CITY: LEXINGTON

ORG_NAME: VA MEDICAL CENTER - LEXINGTON, KY

ORG_STATE: KY

PHR: Pelvic floor disorders (PFDs) is the broad term used to describe a number of conditions that affect millions of women and men in the U.S. Pelvic floor disorders resulting from over- or underactivity of pelvic muscles result in a variety of symptoms, including urinary and fecal incontinence, urinary frequency or urgency, as well sexual problems and pelvic pain syndromes. Despite the common occurrence of PFDs, there is no research examining if PFDs are a problem for men and women with lower limb amputation (LLA). Common impairments of low back pain (LBP), falls, and mobility deficits in people with LLA could be associated with coexisting undiagnosed PFDs. The overall purpose of this research is to better understand the extent at which PFDs occur in Veterans with LLA and any impact on lifestyle and functioning with their prosthesis. The clinical significance of the study will be in establishing an evidence base of PFDs in people with LLA and providing a foundation for future research on the evaluation and treatment of PFDs in people with LLA. Project Narrative

PI_NAMEs: CLEMENS, SHEILA M (contact)

PROJECT_TERMS: Address;Affect;Behavioral;behavioral construct;cohort;Data;design;Disability scale;Distress;Enrollment;Equipment and supply inventories;evidence base;Exhibits;fall risk;falls;Fecal Incontinence;Female;Femur;Genitourinary system;Health;health related quality of life;Impairment;Increased frequency of micturition;Individual;Individuals with physical disabilities;Knowledge;Left;limb amputation;Limb Prosthesis;Low Back Pain;Lower Extremity;male;Measures;men;micturition urgency;Nonpharmacologic Therapy;Outcome Measure;Participant;Patient Self-Report;Pelvic Floor Disorders;Pelvic floor structure;Pelvic Pain;Pelvis;Personal Satisfaction;Persons;Population;Prevalence;Prosthesis;Proxy;Psychometrics;Quality of life;Rehabilitation therapy;remote administration;Reporting;Seminal;sex;Sexual Dysfunction;social;sound;Surveys;Symptoms;Syndrome;Urinary Incontinence;Veterans;Woman;Work

PROJECT_TITLE: Identifying the magnitude and impact of pelvic floor disorders in Veterans with lower limb amputation


ORG_CITY: SALEM

ORG_NAME: SALEM VA MEDICAL CENTER

ORG_STATE: VA

PHR: The implications and impact of this research on Veterans’ health and our healthcare delivery and standard treatment approach is substantial. Untreated PTSD has significant costs for the individual, family, and community, as well as financial and medical costs for the VA. This research moves us toward more equitable and efficient care models that are also effective and greatly enhance treatment access. We propose that effective treatment should greatly enhance quality of life measures and community functioning, while reducing morbidity and suicide rates, substance use, homelessness, PTSD, and depression symptoms. The knowledge gained from this study will provide valuable insights into the functional domains influenced by PTSD-SUD treatment and highlight implementation benefits and challenges so improvements can be made to the assessment and treatment approach. In addition, by examining and addressing any provider, patient, and clinic barriers to implementation, this research can greatly improve the likelihood of successful and wide implementation of a new concurrent treatment approach across residential substance use disorder programs.

PI_NAMEs: HOLOHAN, DANA  (contact)

PROJECT_TERMS: acceptability and feasibility;Address;Aftercare;Age;alcohol use disorder;Attention;Back;Behavior Therapy;Behavioral;Behavioral Model;behavioral outcome;brief intervention;Caring;Clinic;Clinical;clinical practice;Communities;community engagement;comorbidity;Control Groups;cost;craving;Data;depressive symptoms;design;Diagnosis;disability;Dropout;DSM-V;effective therapy;Effectiveness;effectiveness study;effectiveness testing;efficacy evaluation;Enrollment;Ensure;Equity;Ethnic Origin;Evidence based treatment;experience;Family;Feedback;Financial cost;Focus Groups;follow-up;functional outcomes;Future;Gender;Goals;Grant;Health;health care delivery;Health Services Accessibility;high risk;Homelessness;implementation barriers;improved;Individual;insight;Intervention;Interview;Investigation;Knowledge;Length;Measures;Medical Care Costs;Mental Depression;Minority;Modeling;Monitor;Morbidity - disease rate;Outcome;Participant;patient population;Patient Representative;Patient Selection;Patients;Persons;Pilot Projects;Population;Post-Traumatic Stress Disorders;primary outcome;programs;Provider;Quality of life;Randomized;recruit;reduce symptoms;Relapse;Research;response;Risk;Rural;Safety;Sampling;satisfaction;screening;Severities;Shapes;Site;Social Workers;standard care;study population;substance use;Substance Use Disorder;substance use treatment;success;suicidal;Suicide;Suicide attempt;suicide rate;Surveys;symptomatic improvement;Symptoms;Telephone;Trauma;treatment arm;treatment as usual;treatment effect;Treatment outcome;treatment program;trend;United States National Institutes of Health;uptake;Veterans;Woman;World Health Organization Disability Assessment Schedule;Writing

PROJECT_TITLE: Evaluating the Impact of Supplementing Residential Substance Use Treatment with Written Exposure Therapy for Veterans with Co-Occurring PTSD and Substance Use Disorders


ORG_CITY: CANANDAIGUA

ORG_NAME: VETERANS AFFAIRS, UNITED STATES DEPARTMENT OF

ORG_STATE: NY

PHR: Using elements of developed manuals, we will adapt Cognitive-Behavioral Therapy for Loneliness (CBT-L) for delivery to Veterans with chronic pain and conduct a one-arm trial of CBT-L to assess feasibility and treatment acceptability. Data collected from the one-arm trial will be incorporated for a subsequent randomized clinical trial in which Veterans will be randomized to either CBT-L or CBT for Chronic Pain, both delivered via phone, to further assess feasibility, acceptability, and to collect preliminary data on treatment outcomes (loneliness, the quality and quantity of social interactions, and pain outcomes). Findings will be used to inform a larger RR&D merit award to fully powered to assess treatment outcomes.

PI_NAMEs: ASHRAFIOUN, LISHAM  (contact)

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Advertising;Aftercare;arm;Award;Behavior;Behavioral;Behavioral Model;behavioral response;Belief;Chronic Disease;chronic pain;chronic pain management;chronic pain patient;Clinical;Clinical Trials;Cognitive;cognitive testing;Cognitive Therapy;COVID-19 pandemic;Data;depressive symptoms;direct application;effective intervention;efficacy evaluation;efficacy trial;Elements;Emotional;evidence base;Evidence based intervention;experience;Family;Feasibility Studies;Feedback;Feeling suicidal;Fright;Functional impairment;functional improvement;Health Personnel;improved;Individual;innovation;Intervention;Left;Loneliness;Manuals;Measurement;Measures;Mental Depression;Mental Health;Meta-Analysis;Morbidity - disease rate;mortality;negative affect;novel;Outcome;Outcome Assessment;Outcome Measure;Pain;pain catastrophizing;Pain management;pain outcome;pain reduction;pandemic disease;Participant;Pattern;Persons;physically handicapped;Prevention;Problem Solving;Procedures;Process;psychosocial;psychosocial stressors;Randomized;randomized, clinical trials;recruit;Reporting;Research;Research Support;Risk;satisfaction;skills;social;social engagement;Social Environment;Social Functioning;Social Interaction;Social isolation;Social Perception;social situation;Social support;Societies;suicide rate;telehealth;Telephone;Thinking;treatment duration;Treatment outcome;treatment strategy;Veterans;Walking

PROJECT_TITLE: Telehealth CBT to address social isolation in Veterans with chronic pain


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: PHILADELPHIA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Narrative: Mast cells play important roles in host defense and inflammatory diseases through the activation of a newly identified cell surface receptor (MRGPRX2). We have discovered novel pathways via which the function of this receptor is regulated. Understanding the molecular mechanism of its regulation may provide new approaches for the modulation of host defense and inflammatory diseases.

PI_NAMEs: ALI, HYDAR  (contact)

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: adaptive immunity;Adaptor Signaling Protein;Affinity;Agonist;anti-microbial peptide;Bacterial Infections;beta-arrestin;Binding;Biological;cathelicidin antimicrobial peptide;Cell Degranulation;Cell Line;Cell Physiology;Cell surface;Cell Surface Receptors;chemokine;Chronic;chronic inflammatory skin;Clinical;Connective Tissue;Coupling;CRISPR/Cas technology;cytokine;Data;desensitization;Disease;drug action;exome sequencing;FDA approved;G-Protein-Coupled Receptors;gain of function;Generations;GTP-Binding Proteins;Host Defense;Human;IgE Receptors;In Vitro;in vivo;Infection;Inflammation;Inflammatory;Knock-in;Knock-in Mouse;Ligand Binding;Ligands;loss of function;mast cell;Mediating;Mediator;Modification;Molecular;molecular modeling;molecular sequence database;Mus;mutant;Mutation;Natural Immunity;Neuropeptide Receptor;Neuropeptides;Neutrophil Infiltration;novel;novel strategies;Opioid;Opioid Receptor;Pathogenesis;Pathway interactions;Peptides;Pharmaceutical Preparations;Phenotype;pituitary adenylate cyclase activating polypeptide;Play;Procedures;Proteins;Pruritus;Reaction;receptor;receptor coupling;receptor expression;receptor function;recruit;Regulation;response;Role;Rosacea;side effect;Signal Pathway;Signal Transduction;skin disorder;structural determinants;Substance P;transcription factor;Urticaria;Variant;Wild Type Mouse

PROJECT_TITLE: Roles of novel MRGPRX2/MrgprB2 signaling in mast cells on host defense and Inflammation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-T(57)]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Lung;Women's Health Research

ORG_CITY: TUCSON

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Project Narrative This proposal is relevant to public health because more than 30% of breast cancer patients relapse with metastatic disease often fatal due to limited treatment options, presenting an urgent need for innovative strategies to improve patient outcomes. The proposed Cxcl10/Cxcr3/Gbg signaling axis is a novel mechanism of tumor metastasis in the context of breast cancers deficient in the ING4 tumor suppressor. Delineation of the mechanism will offer new therapeutic targets and opportunities for biomarker-guided therapy.

PI_NAMEs: KIM, SUWON  (contact)

PROGRAM_OFFICER_NAME: GRIL, BRUNILDE M

PROJECT_TERMS: Attenuated;Binding;Biological Markers;Breast Cancer Cell;breast cancer metastasis;Breast Cancer Model;Breast Cancer Patient;Breast Cancer Treatment;cancer cell;cancer therapy;Cell Line;Cell Migration Induction;Cell model;cell motility;Cells;chemokine;Clinical Trials;clinically relevant;Co-Immunoprecipitations;Coupled;CRISPR/Cas technology;CXCL10 gene;cytotoxic;Data;Data Set;Disease;Disease-Free Survival;Fatty acid glycerol esters;Future;gallein;Gene Deletion;Gene Expression;gene repression;Genes;GNB1 gene;Goals;Grant;GTP-Binding Proteins;hormone receptor-negative;Human Genome;Immune;Immune response;Implant;improved;In Vitro;Inflammation;Inflammatory;inhibitor;innovation;Knowledge;Laboratories;Leukocytes;Libraries;Lung;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary Neoplasms;Maryland;Mediating;Metastasis Induction;Metastatic breast cancer;Metastatic Neoplasm to the Lung;migration;Migration Assay;Modeling;Molecular;molecular subtypes;mouse model;Mus;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel;novel therapeutics;Oncogenic;Pathway interactions;Patient-Focused Outcomes;Patients;Positive Lymph Node;Prognostic Marker;programs;Public Health;receptor;relapse patients;Repression;Research;Role;Signal Pathway;Signal Transduction;Site;Specificity;targeted treatment;Testing;Therapeutic Intervention;therapeutic target;treatment response;tumor;tumor progression;Tumor Promotion;Tumor Suppressor Proteins;Tumor-infiltrating immune cells

PROJECT_TITLE: Targeting CXCL10 Chemokine Signaling in Breast Cancer Metastasis


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Genetics;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_CITY: IRVINE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE Tissue size control is one of the most fundamental, yet poorly understood problems in modern biology. The proposed work will combine mathematical modeling and experimental manipulations in mice and in vitro to discover how growing hair follicles regulate length of hairs. The results will be directly relevant to the understanding of normal tissue growth, the mechanisms of stem cell control, and the basis for high evolutionary variability of sizes in the same tissue among closely related animal species.

PI_NAMEs: NIE, QING ;PLIKUS, MAKSIM V (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: Affect;Animals;base;Biological;Biology;Cell Communication;Cell Compartmentation;Cell Lineage;Cell Size;cell type;Cells;Communication;Complex;Computer Models;computerized tools;Data;Dermal;Distant;epithelial stem cell;Epithelium;Equilibrium;Experimental Models;experimental study;Feedback;Fibroblast Growth Factor;gene regulatory network;Genes;Genetic;Growth;Hair;Hair Cells;Hair follicle structure;Heterogeneity;In Vitro;in vitro Model;in vivo;Injury;innovation;Knowledge;Length;Link;mathematical model;Mathematics;Mesenchymal;Methods;Microscopic;Modeling;Modernization;Molecular;mouse genetics;Mus;mutant;Mutant Strains Mice;network models;Normal tissue morphology;novel;Organ;Output;overexpression;predictive modeling;Production;progenitor;Proliferating;Regulation;Reproducibility;Research;Role;Signal Pathway;Signal Transduction;Signaling Molecule;single cell sequencing;single-cell RNA sequencing;Site;stem;Stem Cell Research;stem cells;Study models;Testing;tissue regeneration;Tissues;tongue papilla;tool;Transplantation;Work

PROJECT_TITLE: Tissue Size and Precision Control in Growing Hair Follicles

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences;Psychosis;Schizophrenia;Serious Mental Illness

ORG_CITY: SAINT LOUIS

ORG_DEPT: PSYCHIATRY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE About 3% of those in the United States will have a psychotic disorder like schizophrenia which greatly diminishes their quality of life and costs billions of dollars per year to treat. Brain inflammation is thought to be one of the major findings in those with schizophrenia. This proposal validates a safe, new inflammation imaging method in brain samples, and then characterizes brain findings in schizophrenia patients. If this method proves effective, then in the long term, it could be used to predict which young people will develop psychosis and facilitate drug development to treat or even prevent psychotic disorders.

PI_NAMEs: MAMAH, DANIEL  (contact);WANG, YONG

PROGRAM_OFFICER_NAME: MEINECKE, DOUGLAS L

PROJECT_TERMS: Address;Adolescence;aged;Alzheimer's Disease;Anterior;Autopsy;Axon;axon injury;Biological;Brain;brain abnormalities;Brain Diseases;Cellularity;Characteristics;Child;comparison control;Complement;complement system;Corpus Callosum;cost;Data;Delusions;Demyelinations;density;Development;Diffusion;drug development;emerging adult;Encephalitis;Etiology;extracellular;functional decline;Future;Genes;Genetic;genome wide association study;genomic locus;Goals;gray matter;Hallucinations;Hippocampus;histological specimens;imaging biomarker;imaging modality;Imaging Techniques;improved;improved outcome;in vivo;in vivo imaging;Inflammation;Inflammatory;Internal Capsule;Investigation;Limb structure;Longitudinal Studies;Magnetic Resonance Imaging;Major Histocompatibility Complex;Mediating;Methods;Microglia;Multiple Sclerosis;Nerve Degeneration;neuroimaging;neuroinflammation;neuropathology;new therapeutic target;novel;Pathogenesis;Patients;Persons;Phase;Positron-Emission Tomography;Prefrontal Cortex;prevent;Psychoses;Psychotic Disorders;Quality of life;Radiation;Radiation exposure;recruit;Risk;Risk Marker;risk variant;Role;Sampling;Schizophrenia;schizophrenia risk;Serum;Specificity;spectrograph;synaptic pruning;Temporal Lobe;Testing;Tissues;United States;United States National Institutes of Health;Validation;Variant;Water;white matter;Work

PROJECT_TITLE: Validation of Diffusion Basis Spectrum Imaging of Neuroinflammation in Schizophrenia

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Narrative Toxic tau assemblies, oxidative stress, cytoskeletal disruption, and autophagy defects are cardinal features of tauopathies, including Alzheimer’s disease (AD). However, how these cellular phenotypes integrate at the molecular level to produce physiological or pathological responses during tau pathogenesis is unknown. This proposal aims to understand how the intersection between SSH1 and Nrf2 pathways tips the balance between degeneration and protection during proteotoxic and oxidative stress in tauopathies.

PI_NAMEs: KANG, DAVID E (contact)

PROGRAM_OFFICER_NAME: YANG, AUSTIN JYAN-YU

PROJECT_TERMS: Actins;aging process;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid;Animal Model;APP-PS1;Astrocytes;Autophagocytosis;Autopsy;Binding;Binding Sites;Biochemical;Biological Assay;Brain;brain control;Cell Fractionation;Cell model;Cell Nucleus;Cells;cofilin;Cognitive deficits;cohort;Cytoskeleton;Defect;Deposition;Equilibrium;Exhibits;F-Actin;Frontotemporal Lobar Degenerations;Gene Expression;Gene Expression Profile;Genes;Genetic Transcription;Homologous Gene;Human;immunoreactivity;Impaired cognition;In Situ;In Vitro;Induction of Apoptosis;insight;Knowledge;Lentivirus;Ligation;Mediating;Microfilaments;Mitochondria;Molecular;Mus;mutant;Nerve Degeneration;neuroinflammation;Neurons;neuroprotection;Nuclear;Outcome;oxidation;oxidative damage;Oxidative Stress;Pathogenesis;Pathologic;Pathology;Pathway interactions;Phenotype;Phosphoric Monoester Hydrolases;Phosphorylation;Physiological;Protein Dephosphorylation;Proteins;Proteome;Proteomics;proteotoxicity;Recombinant Proteins;Regulation;Repression;response;Rod;sensor;Severities;Signal Transduction;small hairpin RNA;Synapses;tau aggregation;tau Proteins;Tauopathies;Testing;Titrations;transcriptome;transcriptome sequencing;Transfection;ubiquitin-protein ligase

PROJECT_TITLE: SSH1-Nrf2 nexus in tipping the balance between degeneration and protection in tauopathies.

STUDY_SECTION: NOMD

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


ADMINISTERING_IC: HD

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

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: NARRATIVE To date, the etiology of idiopathic male infertility is not fully understood, and there are no FDA-approved hormonal or non-hormonal male contraceptives. Through novel approaches to sequencing and sequencing analysis of male infertile patients and controls, this proposal seeks to identify new coding and non-coding genes and genomic regions required for male fertility. By applying CRISPR/Cas9 in mice to validate the functional requirement and identify the molecular pathophysiology of genes that we identify through our sequencing studies, we will clarify the roles of these new genes in male fertility and infertility and validate targets for future contraceptive studies.

PI_NAMEs: GARCIA, THOMAS  (contact)

PROGRAM_OFFICER_NAME: KENT, TRAVIS JOHN

PROJECT_TERMS: Affect;Alleles;analysis pipeline;Animal Model;Area;Bioinformatics;Biological Process;Biological Specimen Banks;Biology;Blood;Candidate Disease Gene;candidate identification;Cells;Child;Chromosomes;Classification;Clinic;clinical infrastructure;Clinical Management;Code;cohort;Complex;Contraceptive Agents;Contraceptive methods;contraceptive target;Copy Number Polymorphism;Couples;CRISPR/Cas technology;Development;Diagnosis;Diagnostic;empowerment;Etiology;Evaluation;Family;FDA approved;Fertility;Functional disorder;Future;gene product;gene synthesis;gene therapy;Genes;Genetic;Genetic Counseling;genetic testing;genetic variant;Genome;genome sequencing;Genomic Segment;Germ Lines;Goals;Haploid Cells;Haploidy;Haplotypes;Heterozygote;Hormonal;Human;Impairment;improved;Individual;Infertility;Intervention;Investigation;Knowledge;Laboratories;large datasets;Link;loss of function;male;Male Contraceptive Agents;male fertility;Male Infertility;Mediating;Meiosis;men;Methods;Modeling;Molecular;Molecular Abnormality;Molecular Diagnostic Testing;mouse model;Mus;Mutant Strains Mice;Mutation;next generation;novel;novel strategies;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Population;reproductive;Research;Resolution;Role;Sampling;small molecule inhibitor;sperm cell;Spermiogenesis;standard of care;subfertility;technology validation;Therapeutic;Third Generation Sequencing;Time;Translating;transmission process;United States National Institutes of Health;Untranslated RNA;Validation;Variant;Vertebrates;Whole Blood;whole genome;Woman;Work

PROJECT_TITLE: Search for new genes involved in male infertility through novel approaches

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: Columbus

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: OHIO STATE UNIVERSITY

PHR: Project Narrative The proposed study will determine how physical processes of fat delivery from the blood vessels and fat uptake into heart muscle cells determine how these fats are metabolized to support cardiac function, and how these processes contribute to the formation of toxic intracellular fats leading to functional decline in failing hearts. Experiments will examine the delivery of different physiological forms of fat from the circulation to heart muscle cells and how the rates of such delivery determine the way heart muscle metabolizes these fats. Our data indicate that some components of fat uptake by the heart are different between males and females, and we will investigate the fundamental cellular events that contribute to these sex differences and any resulting differences in susceptibility to stress that leads to heart failure in males and females.

PI_NAMEs: LEWANDOWSKI, E DOUGLAS (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Acceleration;Acyl Coenzyme A;Address;Affect;Albumins;Antisense Oligonucleotides;aorta constriction;Awareness;Binding;Blood Vessels;Cardiac;Cardiac Myocytes;Cardiotoxicity;CD36 Antigens;CD36 gene;Cells;Ceramides;Cessation of life;Chronic;Chylomicrons;Circulation;Coenzyme A Ligases;Data;Defect;defined contribution;Dependence;Detection;Endothelial Cells;Endothelium;Energy Metabolism;Enzymes;Esterification;Esterified Fatty Acids;Event;experimental study;Fatty acid glycerol esters;fatty acid metabolism;fatty acid oxidation;Fatty Acids;Female;functional decline;Heart;Heart Diseases;Heart failure;heart function;heart metabolism;Human;Impairment;improved;in vivo;Kinetics;Knockout Mice;Link;lipid metabolism;lipid transport;Lipids;Lipoprotein Binding;long chain fatty acid;male;Mediating;Metabolic;Metabolism;Molecular;mouse model;Mus;Myocardial;Myocardium;Nonesterified Fatty Acids;Outcome;overexpression;oxidation;Pathogenesis;Pathologic;Pathway interactions;physical process;Physiological;Physiological Processes;Predisposition;pressure;Process;Production;Publishing;Research;response;Role;Sarcolemma;sex;Sex Differences;Source;stable isotope;Stress;therapeutic target;trafficking;Transport Process;Triglycerides;uptake;women versus men

PROJECT_TITLE: Transendothelial transport and CD36 in the dysregulated lipid trafficking of failing hearts

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Neurosciences;Pediatric

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Public Summary Regulating stress is critical to healthy mental and physical development. Over the peripubertal period, there appears to be a waning in the effectiveness of social partners to buffer activation of stress-responsive physiological system. The proposed research will determine the neural mechanisms of this effect as well as its pervasiveness, and will potentially improve interventions that support resilience to mental health problems in early adolescence.

PI_NAMEs: GUNNAR, MEGAN R (contact);THOMAS, KATHLEEN M

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TERMS: 14 year old;Address;Adolescence;Adolescent;Adult;Affective;Amygdaloid structure;Attention;attenuation;Autonomic nervous system;biological adaptation to stress;boys;Brain;Brain region;Buffers;Child;Childhood;conditioned fear;Coupling;dehydroepiandrosterone;Development;early adolescence;effective intervention;Effectiveness;Evaluation;Event;experience;experimental study;Failure;Friends;Fright;girls;Goals;Hormones;Human Development;Hydrocortisone;Hypothalamic structure;improved;indexing;Individual;Insula of Reil;Intervention;Knowledge;Mammals;Measures;Mediating;Mental Health;Mood Disorders;neural;Neurobiology;neuromechanism;Neurosecretory Systems;Nurses;Oxytocin;Pain;Parents;Participant;Pathology;Patient Self-Report;Pattern;peer;peripubertal period;Physiological;Pituitary Gland;Process;Psyche structure;Puberty;puberty transition;Regulation;Research;resilience;response;Risk;Role;Safety;Salivary;Sex Differences;social;social relationships;social stress;Social support;Staging;Stimulus;Stress;stress management;stress reactivity;Stressful Event;stressor;System;Teenagers;Testing;Testosterone;Time;urinary;vulnerable adolescent;Work;Youth

PROJECT_TITLE: Social Buffering Over the Pubertal Transition

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Emerging Infectious Diseases;Infectious Diseases;Microbiome;Vector-Borne Diseases

ORG_DEPT: ZOOLOGY

PHR: Project Narrative: Many new methods used to reduce mosquito populations involve a method called sterile insect technique (SIT), in which reproductively sterile males are reared in very large numbers in a laboratory and released to mate with wild females. Here, we hypothesize that bacteria present during immature mosquito development may impact male Aedes aegypti mosquito traits that are relevant for their success in SIT including longevity, body size, and ability to compete for mates. This work will be some of the first to investigate the role of the microbiota in male mosquito fitness traits and will provide key insight into ways the microbiota might be leveraged to improve SIT for mosquito control.

PI_NAMEs: SHORT, SARAH M (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Accounting;Adult;Aedes;Affect;Bacteria;Biology;Body Size;Cessation of life;Communities;Complex;Copulation;Culicidae;Data;Dengue Virus;Development;Dietary Supplementation;Disease;disease transmission;Exposure to;Fat Body;Female;fitness;fungus;Gastrointestinal tract structure;Gland;Gnotobiotic;Goals;immune system function;improved;Insecta;Insemination;insight;Investigation;La Crosse virus;Laboratories;Length;life history;life span;Location;Longevity;male;Male Sterility;Measurement;Methods;Microbe;microbial;microbiota;microbiota composition;Mosquito Control;Mosquito-borne infectious disease;novel;novel strategies;Nutrient;offspring;Organ;Partner in relationship;Pathogenicity;Physiology;Population;prevent;Proteins;Quality of life;Reproduction;reproductive;Reproductive History;reproductive success;Role;Scourge;Seminal fluid;Site;sperm cell;sterile insect technique;Sterility;success;Target Populations;Testing;Time;Tissues;trait;Transcript;transcriptome;transmission process;United States;vector control;Water;West Nile;Wing;Work;Zika Virus

PROJECT_TITLE: The effect of the microbiota on male Aedes aegypti life history traits

STUDY_SECTION: VB

STUDY_SECTION_NAME: Vector Biology Study Section[VB]


NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;HIV/AIDS;Immunization;Infectious Diseases;Orphan Drug;Prevention;Rare Diseases;Tuberculosis;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative The Emory-CDC Clinical Trials Unit is well positioned to contribute to the mission of the NIH HIV/AIDS Clinical Trials Networks due to our extensive experience in conducting clinical trials related to Hepatitis/TB/HIV vaccine, prevention, and treatment both domestically and internationally. We are well suited to participate in pediatric maternal and adult populations. Through our partnerships with the CDC, and our diverse scientific collaborators, we are poised to help develop and implement the next generation of network research plans.

PI_NAMEs: KELLEY, COLLEEN F;OFOTOKUN, IGHOVWERHA  (contact)

PROGRAM_OFFICER_NAME: MEANS, DAVID MICHAEL

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adolescent;Adult;AIDS prevention;Anti-Retroviral Agents;Area;Biological Products;Centers for Disease Control and Prevention (U.S.);Childhood;Cities;Clinic;clinical center;clinical implementation;Clinical Research;clinical research site;Clinical Trials;Clinical Trials Network;Clinical Trials Unit;co-infection;Collaborations;comorbidity;Complex;Conduct Clinical Trials;Country;Development;Disease;Disease remission;Enrollment;Epidemic;experience;flexibility;Funding;Grant;Hepatitis;high risk;HIV;HIV Infections;HIV therapy;HIV vaccine;HIV/AIDS;HIV/TB;human subject;improved;Infection;Inflammation;Institution;International;Intervention;Kenya;Latino;low and middle-income countries;Malignant Neoplasms;member;men;Methods;Mexico;Minority;Mission;National Institute of Allergy and Infectious Disease;Network Infrastructure;next generation;novel;Opportunistic Infections;Organ;Pharmaceutical Preparations;Philippines;Population;Population Heterogeneity;Positioning Attribute;prevent;Prevention;Prevention strategy;Primates;Productivity;programs;Protocols documentation;Public Policy;Recording of previous events;recruit;Research;Research Activity;Research Infrastructure;Research Personnel;Research Subjects;Scientific Advances and Accomplishments;Site;Social Behavior;Strategic Planning;success;support network;Technology;Thailand;Therapeutic;therapeutic vaccine;Translating;Translational Research;treatment strategy;Tuberculosis;tuberculosis treatment;Tuberculosis Vaccines;Underrepresented Populations;United States National Institutes of Health;Universities;vaccine development;Vaccines;volunteer;Woman;working group;Youth

PROJECT_TITLE: Emory-CDC CTU


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Brain Disorders;Genetics;Human Genome;Patient Safety;Precision Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Substance Misuse

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: Project Narrative Acamprosate is an FDA approved drug for the treatment of alcohol use disorder (AUD) in the United States but only a small proportion of AUD patients respond to this drug. The proposed studies have been designed to apply a systematic genome-wide approach using patient-derived stem cells as a novel cellular model system to identify molecular and genomic signatures for AUD as well as mechanisms underlying individual variation in response to acamprosate. The ultimate goal is to advance our understanding of disease pathophysiology and drug action responsible for variation in acamprosate response in AUD patients.

PI_NAMEs: HO, MING-FEN  (contact)

PROGRAM_OFFICER_NAME: FALK, DANIEL EVAN

PROJECT_TERMS: acamprosate;alcohol abuse therapy;Alcohol consumption;alcohol exposure;alcohol response;alcohol use disorder;Alcohols;Applications Grants;biobank;Biological Models;Biomedical Research;Cell Line;Cell model;cell type;Cells;Chromosome 4;Clinical;Clinical Trials;Data;design;Disease;drug action;Ethanol;experience;exposed human population;FDA approved;Functional disorder;functional genomics;Funding;Genes;Genetic;Genetic Markers;genome wide association study;genome-wide;genomic signature;Genomics;Goals;Human;individual variation;individualized medicine;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;induced pluripotent stem cell technology;innovation;insight;K-Series Research Career Programs;Maps;Mental disorders;Mentored Research Scientist Development Award;Mentors;metabolomics;Molecular;Molecular Probes;Molecular Profiling;Multiomic Data;multiple omics;National Institute on Alcohol Abuse and Alcoholism;Nature;Neuroglia;Neurons;non-alcoholic;novel;Outcome;participant enrollment;Pathogenesis;Pathway interactions;patient - derived stem cells;patient derived induced pluripotent stem cells;Patients;Pharmaceutical Preparations;Pharmacogenomics;Pharmacotherapy;Plasma;profiles in patients;Psychiatry;Regulation;Research;Research Personnel;Research Project Grants;Resources;response;Sampling;Selective Serotonin Reuptake Inhibitor;Series;Serotonin;stem cell model;Therapeutic Agents;therapy outcome;Training;transcriptomics;Treatment outcome;treatment response;United States;United States National Institutes of Health;Variant

PROJECT_TITLE: Acamprosate pharmacogenomics: iPSC based model of alcohol use disorder

STUDY_SECTION: AA

STUDY_SECTION_NAME: Clinical, Treatment and Health Services Research Study Section[AA-3]


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

ORG_CITY: STANFORD

ORG_DEPT: GENETICS

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE This research proposal outlines a training plan for becoming an independent cancer researcher with a focus in cancer stem cells (CSCs) and pancreatic cancer (PC). In F99 predoctoral training, I will investigate the role of Pancreatic Differentiation2 (PD2) in pancreatic CSCs and CSC-mediated PC progression, with the goal of deciphering the mechanism of PD2-dependent CSC maintenance. In K00 postdoctoral training, I will focus on investigating the mechanisms that promote the acquisition of different metabolic programs by CSCs and differentiated tumor cells; the molecular biology behind and the contribution of metabolism to CSC-mediated drug resistance; and development of novel combinatorial therapeutics based on metabolic targeting to treat cancer.

PI_NAMEs: KARMAKAR, SASWATI  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: 3-Dimensional;Area;Binding Sites;Cancer Biology;cancer cell;cancer cell differentiation;cancer drug resistance;cancer stem cell;career;Cell Differentiation process;Cell Maintenance;Cell Separation;cell type;Cells;ChIP-seq;Clustered Regularly Interspaced Short Palindromic Repeats;combinatorial;Complex;conventional therapy;CRISPR/Cas technology;Data;Derivation procedure;Development;Disease;Drug resistance;effective therapy;Epigenetic Process;Equilibrium;Exhibits;experimental study;Foundations;Funding;Genes;Genetic;Genomics;Glycolysis;Goals;Human;Implant;improved;in vivo;islet stem cells;knock-down;Knock-out;knockout gene;Knockout Mice;Knowledge;KPC model;Link;lipidomics;Maintenance;Malignant neoplasm of ovary;Malignant neoplasm of pancreas;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Mentors;Messenger RNA;Metabolic;metabolic phenotype;metabolic profile;Metabolism;metabolomics;Mitochondria;Modeling;Molecular;Molecular Biology;Mouse Embryonic Stem Cells;Mus;Neoplasm Metastasis;neoplastic;neoplastic cell;novel;Nude Mice;Oncogenes;Organoids;overexpression;oxidation;Oxidative Phosphorylation;Pancreas;pancreatic cancer cells;pancreatic cancer model;pancreatic differentiation 2 protein;pancreatic tumorigenesis;Pathogenesis;Pathway interactions;Phase;Phenotype;Play;Polymerase;Population;post-doctoral training;Postdoctoral Fellow;pre-doctoral;programs;Protein Dynamics;Proteins;Proteomics;Pyruvate;Recurrence;Research;Research Personnel;Research Project Grants;Research Proposals;RNA Polymerase II;Role;self-renewal;skills;stem cell biomarkers;stem cell self renewal;stem cells;stemness;targeted treatment;Techniques;Therapeutic;therapeutic target;Tissues;Training;Transcription Elongation;transcription factor;transcriptome sequencing;Transgenic Mice;Tumor Burden;tumor heterogeneity;tumor metabolism;tumor progression;Tumor Tissue;tumorigenesis;United States;Work

PROJECT_TITLE: Pancreatic cancer stem cells: PD2-mediated novel mechanistic link and metabolomic alterations


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_DEPT: NEUROLOGY

PHR: Project Narrative How do neurons coordinate alternative energy sources to meet  the demands of neural computation? PI:Clandinin  The brain is energetically expensive, a metabolic cost that is intrinsic to neural activity and hence a defining feature of how the brain computes. This project develops an experimental system in which energy production can be linked to single neurons, integrated circuits and across the entire brain. These studies will therefore broadly inform the development of therapeutic strategies to treat neural impacts of metabolic disease.

PI_NAMEs: CLANDININ, THOMAS ROBERT (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TERMS: Adult;Affect;Anatomy;Animals;Axon;Behavior;Biochemical Pathway;Blood flow;Brain;Brain imaging;cell type;Cells;cost;Couples;Coupling;Dendrites;Disease;Drosophila genus;Elements;energy balance;Energy consumption;Energy Metabolism;Energy-Generating Resources;Esthesia;Expenditure;fluorescence imaging;fly;Functional Magnetic Resonance Imaging;Future;Genes;Genetic;Glucose;Glycolysis;Goals;Human;imaging modality;In Vitro;in vitro Model;in vivo;Individual;insight;integrated circuit;Investigation;Link;Measures;Metabolic;Metabolic Diseases;metabolic imaging;Metabolism;Methods;Mitochondria;Modeling;Monitor;Movement;neural;neural patterning;neuroimaging;Neurologic;Neurons;neuroregulation;Neurosciences;neurotransmission;novel therapeutics;operation;optogenetics;Oxidative Phosphorylation;Pathway interactions;Pattern;Perception;Physiological;Positron-Emission Tomography;Production;Proxy;Publishing;Pyruvate;Reaction;sensor;Sensory;sensory input;sensory stimulus;Shapes;Signal Transduction;stereotypy;System;Testing;therapeutic development;Time;two-photon;Work

PROJECT_TITLE: How do neurons coordinate alternative energy sources to meet the demands of computation?


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

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: γ-Secretase is a protease that cleaves the amyloid precursor protein (APP) to generate Aβ peptides, contributing to the pathogenesis of Alzheimer’s disease (AD). We have limited understanding of γ-secretase's mechanism of action. Here, we will take an interdisciplinary approach to investigate how modulatory factors regulate γ- secretase activity, which will deliver molecular insights into γ-secretase catalysis and regulation that are critical for both basic and translational AD research.

PI_NAMEs: FENG, LIANG ;LI, YUEMING  (contact)

PROJECT_TERMS: Abeta synthesis;Acids;Active Sites;Affect;Allosteric Regulation;Alzheimer's Disease;American;Amyloid beta-Protein;Amyloid beta-Protein Precursor;amyloid peptide;amyloid precursor protein processing;Architecture;Binding;Biochemical;Biology;Catalysis;Catalytic Domain;Cellular biology;Chemicals;Cholesterol;Complex;Dementia;design;Detergents;disease-causing mutation;effective therapy;Environment;environmental change;familial Alzheimer disease;Foundations;functional outcomes;gamma secretase;Healthcare Systems;Hypoxia;inhibitor;insight;interdisciplinary approach;Investigation;Label;Link;Lipid Bilayers;Lipids;Membrane;Membrane Lipids;Micelles;Modeling;Molecular;Molecular Conformation;Molecular Probes;Movement;Mutation;nanobodies;nanodisk;Neurodegenerative Disorders;next generation;novel;novel strategies;Pathogenesis;Pathogenicity;Pathologic;Peptide Hydrolases;Peptides;presenilin;prevent;Production;Proteins;Reaction;Reagent;Regulation;Research;Resolution;response;Role;secretase;Site;small molecule;Societies;Specificity;structural biology;Structure;therapeutic development;therapy development;Thick;tool;Transmembrane Domain

PROJECT_TITLE: Molecular mechanisms of gamma-secretase modulation central to Alzheimer’s  disease

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


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

PHR: PROJECT NARRATIVE  Neurofibrillary tangles composed of hyperphosphorylated and aggregated Tau protein are a major pathological hallmark of Alzheimer’s disease. Despite the strong clinical association, how wildtype human Tau proteins become hyperphosphorylated and cytotoxic remains poorly understood. This project will investigate the role of mRNA export complex TREX2 in detoxification of human Tau overexpression in the budding yeast Saccharomyces cerevisiae and establish a novel Tau cytotoxicity model in this simple model organism, which will serve as a platform for unbiased genetic suppressor screen for Tau cytotoxicity.

PI_NAMEs: DANG, WEIWEI  (contact)

PROJECT_TERMS: Adopted;alpha synuclein;Alzheimer's Disease;Antibodies;Biochemical;biological adaptation to stress;Biological Assay;Categories;cell type;Cells;Clinical;Collaborations;Complex;cytotoxic;cytotoxicity;Data;Databases;Defect;Deletion Mutation;Dementia;detection sensitivity;differential expression;Disease;Drosophila genus;Drug Metabolic Detoxication;Eukaryotic Cell;Expression Library;fluorescence imaging;Fluorescence Resonance Energy Transfer;fly;Frontotemporal Dementia;Future;Galactose;Gene Expression;Genes;Genetic;Genetic Screening;Genetic Transcription;genetic variant;Genomics;Growth;Human;knock-down;Letters;Measures;Microfluidic Microchips;Microfluidics;misfolded protein;model organism;Modeling;Molecular;Molecular Conformation;mRNA Export;mutant;Mutate;Nature;Neurodegenerative Disorders;Neurofibrillary Tangles;Neurons;novel;Open Reading Frames;overexpression;Parkinson Disease;Pathologic;Pathology;Pathway interactions;Phenotype;Physiological;Pilot Projects;protein aggregation;protein complex;protein expression;protein misfolding;Proteins;Repression;response;Role;Saccharomyces cerevisiae;Saccharomycetales;Stress;stressor;tau aggregation;tau conformation;tau expression;tau Proteins;tau-1;Tauopathies;Technology Transfer;Testing;tool;Toxic effect;transcriptome;transcriptome sequencing;TREX2 gene;Validation;Variant;Western Blotting;yeast genetics;Yeast Model System;Yeasts

PROJECT_TITLE: Developing and Validating a Novel Tau Toxicity Model in the Budding Yeast

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Methamphetamine;Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_DEPT: PHARMACOLOGY

PHR: PROJECT NARRATIVE Methamphetamine is a highly addictive psychostimulant that is also capable of inducing neuronal damage; prior and pilot studies showed that chronic methamphetamine administration resulted in degeneration of substantia nigra pars compacta dopamine and locus coeruleus norepinephrine neurons. The mechanism by which chronic methamphetamine drives degeneration of these neuronal populations and the behavioral consequences are unclear. Our studies are aimed at investigating the pattern and progression of chronic methamphetamine-induced degeneration, the mechanism that drives degeneration, and the behavioral dysfunction resultant from chronic methamphetamine-induced degeneration of substantia nigra pars compacta and locus coeruleus neurons.

PI_NAMEs: PILSKI, ALEXANDER N (contact)

PROGRAM_OFFICER_NAME: FALCON-MORALES, EDGARDO

PROJECT_TERMS: Astrocytes;Attenuated;Automobile Driving;Axon;axon injury;axonal degeneration;Back;Behavioral;behavioral impairment;Biological Assay;career;Catecholamines;Chronic;conditioned fear;CRISPR/Cas technology;Cytosol;Data;Deamination;Dependence;Disease;Dopamine;dopaminergic neuron;Enzymes;Functional disorder;Genetic;genetic manipulation;Goals;Immunofluorescence Immunologic;Impaired cognition;Impairment;improved;Induced Neurons;Knock-out;Knowledge;Length;Lesion;locus ceruleus structure;Mentors;Metabolism;Methamphetamine;Mitochondria;Monoamine Oxidase;Morphology;multidisciplinary;Mus;Nerve Degeneration;neuronal cell body;Neurons;neuroprotection;Neurosciences;Neurotransmitters;Norepinephrine;novel;object recognition;pars compacta;Pattern;pharmacologic;Pilot Projects;Population;prevent;Process;Proteins;psychostimulant;Reactive Oxygen Species;Research;Saline;Scientist;Severities;Stimulant;Stress;Substantia nigra structure;Techniques;Testing;Training;Vesicle;vesicular monoamine transporter 2

PROJECT_TITLE: Chronic methamphetamine-induced catecholaminergic degeneration and cognitive dysfunction


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Biotechnology;Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: JACKSONVILLE

ORG_NAME: MAYO CLINIC  JACKSONVILLE

ORG_STATE: FL

PHR: The mislocalization and abnormal aggregation of the protein TDP-43 is a hallmark of pathology in the related neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which is an Alzheimer’s disease related dementia (ADRD). Pathological aggregates of insoluble TDP-43 protein are also commonly found in Alzheimer’s disease  and other devastating disorders. Here we propose to study how specific nuclear-import receptor proteins (importins) can act as molecular chaperones that restore solubility, nuclear localization, and normal function to TDP-43, and prevent neurodegeneration in cellular and animal models of FTD and ALS.

PI_NAMEs: ROSSOLL, WILFRIED  (contact);SHORTER, JAMES

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: Address;Alzheimer's Disease;Alzheimer's disease related dementia;Amyotrophic Lateral Sclerosis;Animal Model;Autopsy;Biochemical;Biological Assay;Brain;brain tissue;Cell Culture Techniques;Cell model;Cell Nucleus;Cell Physiology;Complement;Complex;Cytoplasm;Data;Defect;design;Disease;disease phenotype;Drosophila genus;effective therapy;Engineering;experimental study;Feedback;fly;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;Future;gain of function;Gene Transfer Techniques;Goals;Human;human disease;Importins;In Vitro;in vivo;in vivo Model;Karyopherins;Knowledge;Liquid substance;loss of function;Methods;Modeling;Molecular;Molecular Chaperones;mouse model;mutant;Nature;Nerve Degeneration;Neurodegenerative Disorders;Neurons;neuropathology;novel;novel therapeutic intervention;Nuclear;Nuclear Import;Nuclear Pore Complex Proteins;nucleocytoplasmic transport;Orthologous Gene;Outcome;Pathogenesis;Pathologic;Pathology;Patients;Phase;Phase Transition;Phenotype;Physiological;prevent;prion-like;Process;protein aggregation;Protein Engineering;protein TDP-43;Proteins;proteotoxicity;receptor;receptor function;Recombinant Proteins;recruit;Reporting;Ribonucleoproteins;RNA Splicing;RNA-Binding Proteins;Role;Secondary to;Slice;Solubility;structural biology;targeted treatment;TDP-43 aggregation;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;therapy development;Tissues;Toxic effect;Variant

PROJECT_TITLE: Nuclear import receptors as modifiers of TDP-43 phase transition and toxicity in FTD/ALS


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;Mental Health;Neurodegenerative;Neurosciences;Patient Safety

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

ORG_STATE: MA

PHR: Project Narrative Delirium (acute confusion), a major complication of surgery in older patients, is often followed by long term decline in memory and thinking, ultimately leading to Alzheimer's dementia in some individuals. To shed light on the mechanisms underlying these associations, our project will use proteomics, a technique measuring levels of 7000 proteins in blood, and previously collected clinical data and biospecimens from the Successful Aging after Elective Surgery (SAGES) I and II studies, to determine whether a panel of proteins associated with future development of Alzheimer's Disease, and separate protein panels associated with accelerated aging, predict delirium and delirium with cognitive decline. We will also develop (SAGES I) and independently test (SAGES II) new protein predictor panels for delirium and long term decline after delirium.

PI_NAMEs: LIBERMANN, TOWIA A.;MARCANTONIO, EDWARD R (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Acceleration;Acute;Acute-Phase Proteins;Address;Age;age acceleration;age effect;Aging;aging clocks;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Biological;Biological Aging;Biological Specimen Banks;biomarker discovery;Blood;blood-based biomarker;Brain;Cessation of life;Characteristics;Chronology;Clinical;Clinical Data;cohort;Complex;Confusion;Delirium;Development;Enzyme-Linked Immunosorbent Assay;follow-up;Functional disorder;Funding;Future;hospital readmission;Hyperactivity;Impaired cognition;improved outcome;Individual;Inflammation;Inflammatory;Inflammatory Response;insight;Intervention;Investments;Measures;Memory;Modeling;Molecular;multiple omics;National Institute on Aging;Neuronal Injury;Nursing Homes;older adult;older patient;Operative Surgical Procedures;Outcome;Pathogenesis;Pathway interactions;Patients;Plasma;Plasma Proteins;postoperative delirium;Postoperative Period;precision medicine;predictive panel;predictive signature;Predisposing Factor;Predisposition;Prevention;prognostication;programs;Proteins;Proteome;proteomic signature;Proteomics;Risk;risk prediction;Schedule;Surgical complication;Techniques;Testing;tetrahydrobiopterin;Thinking;Validation

PROJECT_TITLE: AD/ADRD and biological aging proteomic signatures in the etiopathology of delirium and its associated long-term cognitive decline

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


NIH_SPENDING_CATS: Antimicrobial Resistance;Clinical Research;Clinical Trials and Supportive Activities;Infectious Diseases;Orphan Drug;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: Los Angeles

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE We will examine the preliminary efficacy of oral linezolid 600 mg in treating early syphilis. The results of this clinical trial may identify linezolid as a potential treatment for syphilis that could be useful in cases of penicillin shortage and allergy. We will also test linezolid against several types of syphilis strains in the lab.

PI_NAMEs: KLAUSNER, JEFFREY DAVID (contact)

PROGRAM_OFFICER_NAME: CHUANG, ELEANORE JENNIFER

PROJECT_TERMS: Address;Adherence;Adult;Aftercare;Allergic;alternative treatment;Animals;Antibiotic Therapy;Antibiotics;arm;Bacteria;bactericide;Benzathine Penicillin;Case Series;Cefixime;Ceftriaxone;Cephalosporins;Cerebrospinal Fluid;Clinic;Clinical;clinical efficacy;Clinical Research;clinical research site;Clinical Trials;Collection;Control Groups;cost;Country;Data;Data Analyses;Data Collection;data dissemination;Development;Dose;Doxycycline;Drug Kinetics;Drug resistance in tuberculosis;Early treatment;effective therapy;efficacy evaluation;Enrollment;experience;experimental arm;experimental study;FDA approved;follow-up;Funding;Generations;Globus Pallidus;Gram-Positive Bacteria;healing;HIV Infections;Hour;Human;Hypersensitivity;In Vitro;Incidence;Individual;Infectious Skin Diseases;Injectable;Injections;instrument;International;Intramuscular;Lesion;Linezolid;men who have sex with men;methicillin resistant Staphylococcus aureus;microbicide;Minimum Inhibitory Concentration measurement;Modeling;Monitor;novel;novel strategies;open label;Oral;Oral Administration;Oral cavity;Oryctolagus cuniculus;Outcome;Oxazolidinones;Participant;participant enrollment;Patients;Penicillin Allergy;Penicillin G;Penicillins;Persons;Peru;Phase;Pilot Projects;pilot trial;Pneumonia;Predisposition;Pregnancy;Randomized;Randomized, Controlled Trials;Recommendation;recruit;Regimen;Research;research clinical testing;response;Safety;Sampling;Scheme;Serology;Serology test;Site;Specimen;Streptococcus;success;Syphilis;System;Testing;Tetracyclines;Time;Toxic effect;Training;treatment duration;Treponema pallidum;United States National Institutes of Health;Vancomycin resistant enterococcus;Work

PROJECT_TITLE: Pilot study of linezolid for early syphilis treatment

STUDY_SECTION: CRFS

STUDY_SECTION_NAME: Clinical Research and Field Studies of Infectious Diseases Study Section[CRFS]


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: PROJECT NARRATIVE PPARγ is an important transcription factor which has anti-oxidant and anti-inflammatory effects in the kidney and provides protection against risk factors such as a high salt diet. Little is known about the downstream pathways that PPARγ activates in renal microvessels and their mechanisms of action in combating oxidative stress and promoting sodium excretion. We hypothesize that PPARγ regulates renal hemodynamics and salt sensitivity through suppressing prostaglandin E receptor 3 expression and controlling redox balance in renal microvessels and when impaired induces renal dysfunction leading to salt sensitive hypertension.

PI_NAMEs: WU, JING O. (contact)

PROGRAM_OFFICER_NAME: RANKIN, TRACY L

PROJECT_TERMS: absorption;Academia;Animals;antagonist;Antiinflammatory Effect;Antioxidants;Arteries;arteriole;Attenuated;Biological Availability;Biology;blood glucose regulation;Blood Pressure;blood pressure reduction;Blood Vessels;Cardiovascular system;Cells;Cerebrovascular Circulation;Chronic Kidney Failure;Clinical Research;cofactor;Compensation;Data;Development;Dinoprostone;Dominant-Negative Mutation;early onset;Epithelium;Equilibrium;Excess Dietary Salt;Excretory function;Exhibits;Functional disorder;Furosemide;Generations;Genes;Genetic;Goals;Grant;hemodynamics;high salt diet;Human;Hypertension;Impairment;improved;Individual;innovation;Interlobular Artery;Kidney;kidney dysfunction;kidney vascular structure;Ligands;Macrophage;Mediating;Mentored Research Scientist Development Award;Mentors;Metabolic syndrome;Modeling;mortality;Mus;Mutation;Myocardial Infarction;Natriuresis;Nitric Oxide;Nitric Oxide Synthase;Non-Insulin-Dependent Diabetes Mellitus;NOS1 gene;NOS2A gene;novel;Oxidation-Reduction;Oxidative Stress;pathogen;Pathway interactions;Perfusion;pharmacologic;Pharmacology;Physiology;PPAR gamma;prevent;Production;programs;Prostaglandin E Receptor;Prostaglandins;Protein Isoforms;Publishing;Reactive Oxygen Species;receptor;Receptor Signaling;Renal Blood Flow;Research;Resistance;response;Risk Factors;Role;salt intake;salt sensitive hypertension;Scientist;selective expression;Signal Transduction;skills;Sodium;Sodium Chloride;Stroke;Superoxides;symporter;Testing;Thiazolidinediones;transcription factor;Transcriptional Regulation;Tubular formation;Vascular Endothelium;Vascular resistance;Vascular Smooth Muscle;Vasodilation;Water

PROJECT_TITLE: Novel Mechanisms Regulating Renal Perfusion and Kidney Redox Biology: Role in Salt Sensitive Hypertension

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Kidney, Urologic and Hematologic Diseases D Study Section[DDK-D]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Recent studies have improved the clinical and neuropathological diagnostic criteria to recognize the distinct clinical subtypes of progressive supranuclear palsy (PSP); however, recent cryo-EM work and a revision of neuropathologic findings led to the discovery of novel 4R tauopathies, previously considered PSP. The main goals of this project are to elucidate the prevalence of these novel entities in a large cohort of PSP cases, perform structural studies and determine pathological mechanisms implicated in tau propagation in vivo and in vitro using novel  technologies and model systems. The investigation of what drives the specificity of tau conformers in tau pathology is an essential step toward the design of novel diagnostic and therapeutic molecules.

PI_NAMEs: GHETTI, BERNARDINO FRANCESCO;KOVACS, GABOR GEZA;VIDAL, RUBEN  (contact)

PROJECT_TERMS: Address;Affect;Alzheimer's Disease;Astrocytes;Behavioral;behavioral impairment;Biochemical;Biological Models;Brain;Brain region;Categories;Clinical;clinical diagnosis;clinical subtypes;cohort;Coiled Bodies;Collection;conformer;corticobasal degeneration;Cryoelectron Microscopy;Custom;Deglutition Disorders;design;Diagnosis;diagnostic criteria;Disease;Filament;frontal lobe;Frontotemporal Dementia;gaze;gaze palsy;Genetic;genetic analysis;Goals;Guidelines;Hippocampus;Histologic;Human;immunoreactivity;Impaired cognition;improved;In Vitro;in vivo;in vivo Model;Inclusion Bodies;Indiana;Individual;Investigation;Lead;Microfluidic Microchips;Modeling;Molecular;Molecular Conformation;mouse model;Movement;multidisciplinary;Mus;Names;Nerve Degeneration;neurodegenerative dementia;Neurofibrillary Tangles;Neurons;neuropathology;Neuropil Threads;new technology;novel;novel diagnostics;novel therapeutics;Pathologic;Pathology;Pathway Analysis;Patients;Pattern;Pick Disease of the Brain;Polymorph;Post-Translational Protein Processing;posture instability;Prevalence;Progressive Supranuclear Palsy;Resolution;Specificity;Structure;Symptoms;tau aggregation;tau Proteins;Tauopathies;technology platform;Therapeutic Studies;Time;Validation;Variant;Work

PROJECT_TITLE: Identification of novel four repeat tauopathies through analysis of network vulnerability, tau structure and propagation.


ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: PROJECT NARRATIVE Our long-term goal is to improve cancer diagnoses and the early response to anti-cancer treatments using Magnetic Resonance Fingerprinting (MRF). To meet our goal, we will develop and validate new dynamic 3D MRF and methods to accurately and precisely measure tumor vascular perfusion in rodent models of human cancers that are treated with established cancer therapies. We will also develop a new pHe-MRF method that can accurately measure extracellular tumor pH (pHe) in different tumor types and to monitor changes in tumor pHe in response to therapy using two co-administered MRI contrast agents.

PI_NAMEs: FLASK, CHRISTOPHER A (contact);PAGEL, MARK DAVID

PROGRAM_OFFICER_NAME: ZHANG, HUIMING

PROJECT_TERMS: 3-Dimensional;Acidosis;Address;Algorithms;Animal Model;Animals;anti-cancer treatment;Bicarbonates;Biometry;Blood Vessels;Breast Cancer Model;cancer diagnosis;Cancer Model;Cancer Patient;cancer therapy;Clinic;clinical translation;clinically relevant;Combretastatin A4 Phosphate;contrast enhanced;Contrast Media;design;Development;Dictionary;Dose;Drug Kinetics;Early Diagnosis;Environment;Esomeprazole;Evaluation;experience;experimental study;extracellular;Fingerprint;Goals;Histopathology;human model;Hypoxia;Image;imaging modality;improved;in vivo;Injections;innovation;Lead;Magnetic Resonance;Magnetic Resonance Imaging;Malignant Neoplasms;Maps;Measurement;Measures;metaiodobenzylguanidine;Metformin;Methodology;Methods;Microelectrodes;Modeling;Monitor;Mus;novel strategies;pancreas xenograft;pancreatic neoplasm;Patients;Perfusion;preclinical imaging;Preparation;Quantitative Evaluations;Radiation therapy;Radiology Specialty;Recovery;Relaxation;Reporting;Reproducibility;Research;Research Personnel;response;Rodent Model;Series;Solid Neoplasm;Techniques;temporal measurement;Therapeutic;Translating;treatment response;tumor;tumor diagnosis;tumor microenvironment;Validation;Variant;Xenograft procedure

PROJECT_TITLE: Magnetic Resonance Fingerprinting of Tumor Vascular Perfusion and Acidosis

STUDY_SECTION: EITA

STUDY_SECTION_NAME: Emerging Imaging Technologies and Applications Study Section[EITA]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Biotechnology;Climate-Related Exposures and Conditions;Genetics;Human Genome

ORG_CITY: PORTLAND

ORG_DEPT: BIOLOGY

ORG_NAME: PORTLAND STATE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative:  UV radiation (254nm light) induces DNA damage that blocks replication can result in genomic rearrangements when it resumes from the wrong place, mutagenesis when the incorrect base is incorporated opposite to the lesion, or cell death when the block to replication cannot be overcome. Inaccurate replication in the presence of environmental mutagens such as UV is responsible for the majority of mutagenesis and rearrangements observed in cancer cells. Here, we propose to characterize a mechanism by which repair of the blocking lesion is coupled to the disrupted replication fork that allows faithful replication to resume and cells to survive, while avoiding mutations or rearrangements.

PI_NAMEs: COURCELLE, JUSTIN  (contact)

PROGRAM_OFFICER_NAME: SHAUGHNESSY, DANIEL

PROJECT_TERMS: Bacteria;base;BRCA2 gene;cancer cell;Cell Death;Cell Physiology;Cell Survival;Cells;Clinical;Coupled;Coupling;DNA biosynthesis;DNA Damage;DNA lesion;DNA Repair;DNA replication fork;DNA Sequence Rearrangement;efficacy validation;environmental mutagens;Escherichia coli;Event;gene product;Genetic Recombination;Genome;genome integrity;Genome Stability;genome-wide;Growth;Health;High-Throughput Nucleotide Sequencing;Homologous Gene;Human;In Vitro;inhibitor;Lesion;Light;Malignant Neoplasms;Maps;Mediating;Microsatellite Instability;Modeling;Mutagenesis;mutant;Mutate;Mutation;Nucleotide Excision Repair;Outcome;Pathway interactions;Plasmids;Play;Poly(ADP-ribose) Polymerase Inhibitor;prevent;Process;Proteins;Recovery;recruit;repair enzyme;repaired;Replication-Associated Process;Reporting;response;Role;targeted cancer therapy;Therapeutic;Time;ultraviolet damage;ultraviolet irradiation;ultraviolet lesions;Ultraviolet Rays;UV induced DNA damage;Work

PROJECT_TITLE: Replication-Coupled Repair: a mechanism for surviving UV irradiation

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Nanotechnology;Neurosciences;Orphan Drug;Radiation Oncology;Rare Diseases

ORG_CITY: BALTIMORE

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Project Narrative The brain cancer, glioblastoma (GBM), is among the most heterogeneous, treatment resistant, and lethal of all human cancers. The complexity of GBM and our slow progress in effectively treating this disease warrant new combination treatment strategies that leverage tools and technologies earlier in the disease management and during the time of surgical intervention. Here, we propose to test a combination intra-operative, image-guided treatment regimen where we use targeted gold nanoparticles to improve laser interstitial thermal therapy for GBM.

PI_NAMEs: HUANG, HUANG CHIAO ;KIM, ANTHONY J.;WINKLES, JEFFREY A;WOODWORTH, GRAEME F (contact)

PROGRAM_OFFICER_NAME: AVULA, LEELA RANI

PROJECT_TERMS: Ablation;Acceleration;Adhesives;Adverse effects;Adverse event;Antibodies;Binding;Biology;Blood - brain barrier anatomy;Brain;Brain Edema;Brain Injuries;Brain Neoplasms;brain tissue;Bypass;cancer cell;Cell Death;Cells;chemotherapy;Clinical;clinical efficacy;Clinical Research;clinical translation;Clinical Trials;Combined Modality Therapy;Complex;Development;Disease;Disease Management;Drug Delivery Systems;efficacy evaluation;Electric Capacitance;experience;Fibroblast Growth Factor;Formulation;Glioblastoma;Heating;Human;image guided;immunodeficiency;Implant;improved;in silico;In Vitro;in vivo;interstitial;Invaded;Knowledge;Lasers;local drug delivery;Magnetic Resonance Imaging;Malignant neoplasm of brain;Malignant Neoplasms;member;minimally invasive;Modeling;Monitor;multidisciplinary;nanoGold;nanoparticle;Nanotechnology;nanotherapeutic;neuro-oncology;neurosurgery;Normal tissue morphology;novel;novel strategies;Operative Surgical Procedures;patient derived xenograft model;Patients;Penetration;phase I trial;photothermal therapy;plasmonics;Polyethylene Glycols;preclinical efficacy;preclinical safety;Publishing;Radiation;Radiation therapy;Radiosensitization;Rat Transgene;Rattus;receptor;Recurrent tumor;Resistance;response;Robotics;Rodent;Safety;Seizures;side effect;Solid Neoplasm;spatiotemporal;Technology;Temperature;Testing;therapy resistant;Thermal Ablation Therapy;Thermometry;Time;tool;translational approach;Treatment Protocols;treatment strategy;tumor;Tumor Necrosis Factor Receptor;Tumor Tissue;Unresectable;virtual;X-Ray Computed Tomography

PROJECT_TITLE: Nanotherapeutic enhancement of interstitial thermal therapy for glioblastoma

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


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

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Staphylococcus aureus is a prominent bacterial pathogen that causes persistent pneumonias in patients with preexisting lung disease, driving a decline in lung function and an increased risk of mortality. A key component of the immune response to pathogens is the production of regulatory metabolites like itaconate, which regulates inflammation and bacterial clearance. This proposal aims to investigate the role of itaconate in the host immune response and bacterial adaptation during S. aureus lung infection, with the goal of uncovering pathways that underlie inflammation and staphylococcal persistence that can be targeted by future therapies.

PI_NAMEs: TOMLINSON, KIRA LEIGH (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Address;Anti-Inflammatory Agents;Antibiotic susceptibility;antibiotic tolerance;Antibiotics;Antiinflammatory Effect;antimicrobial;Automobile Driving;Bacteria;bacterial metabolism;biological adaptation to stress;Biological Assay;Bronchoalveolar Lavage Fluid;Carbon;Cell Separation;cell type;Cells;Chronic;Clinical;clinically relevant;Communities;cytokine;Data;differential expression;Elements;Energy Metabolism;Environment;Enzymes;Equilibrium;Exhibits;Exposure to;Flow Cytometry;Future;Genes;Genetic Transcription;Genus staphylococcus;Glycolysis;Goals;Growth;Immune;Immune response;immunoregulation;In Vitro;in vivo;Infection;Inflammation;Inflammatory;Lung;Lung Diseases;Lung infections;Macrophage;Mediating;Mediator;Metabolic;Metabolic stress;Metabolism;metabolomics;Microbial Biofilms;Modeling;Monitor;mortality risk;Mus;neutrophil;Nosocomial pneumonia;pathogen;Pathogenesis;pathogenic bacteria;Pathway interactions;Patients;Phagocytes;Phagocytosis;Phenotype;Play;Pneumonia;Population;Predisposition;Production;pulmonary function;Pulmonary Inflammation;Quantitative Reverse Transcriptase PCR;recruit;Reporting;Respiratory Burst;response;Role;Signal Transduction;single-cell RNA sequencing;Source;Staphylococcal Pneumonia;Staphylococcus aureus;Staphylococcus aureus infection;Stimulus;Structure of parenchyma of lung;synthetic enzyme;Testing;Therapeutic;Tissues;Training;Western Blotting

PROJECT_TITLE: The immunometabolite itaconate drives S. aureus lung infection


NIH_SPENDING_CATS: Autism;Brain Disorders;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Network analysis suggests that high confidence autism spectrum disorder (hcASD) genes operate through convergent mechanisms that predominantly modulate chromatin remodeling or support synaptic function, which in turn can determine anatomical and functional brain connectivity. However, how the proteins encoded by these genes interact physically and converge functionally has not been fully elucidated. The studies we propose aim to determine the postsynaptic interactome of ankyrin-B, which is encoded by the high confidence autism gene ANK2.

PI_NAMEs: LORENZO, DAMARIS N (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: Action Potentials;Affect;Anatomy;ANK2 gene;Antibodies;Architecture;ASD patient;autism spectrum disorder;Axon;axon growth;Binding;Biological Assay;Biology;Biotin;Brain;Cells;Cellular Assay;chromatin remodeling;Complex;Couples;Cytoskeletal Proteins;Dendrites;density;Development;disorder risk;excitatory neuron;Exhibits;experimental study;falls;Functional disorder;gene interaction;gene network;Genes;Glutamates;Goals;high risk;hippocampal pyramidal neuron;Impairment;In Vitro;in vivo;individuals with autism spectrum disorder;Ion Channel;Knock-in Mouse;Knockout Mice;Label;Ligase;Link;Mass Spectrum Analysis;Membrane;Membrane Proteins;Membrane Transport Proteins;Molecular;Morphology;Motor;Mus;nanoscale;Neurons;novel;Pathway Analysis;Pathway interactions;Phenocopy;Play;Positioning Attribute;postsynaptic;postsynaptic density protein;protein complex;Protein Isoforms;Proteins;Proteomics;Publishing;Role;Scaffolding Protein;SCN2A protein;Sodium Channel;superresolution imaging;superresolution microscopy;Synapses;synaptic function;Synaptic Transmission;tandem mass spectrometry;trafficking;Variant;Vertebral column;Vesicle;voltage

PROJECT_TITLE: Elucidating the synaptic interactome of the high risk autism gene ANK2

STUDY_SECTION: SYN

STUDY_SECTION_NAME: Synapses, Cytoskeleton and Trafficking Study Section[SYN]


ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

PHR: Project Narrative  Abdominal aortic aneurysm, a permanent dilation of the abdominal aorta, with a high mortality rate of over 80% after rupture. Using novel mouse models that we have developed, our goals are to elucidate mechanisms responsible for AAA formation and identify new targets for therapeutic development against AAAs.

PI_NAMEs: SUBRAMANIAN, VENKATESWARAN  (contact)

PROGRAM_OFFICER_NAME: GALIS, ZORINA S

PROJECT_TERMS: 3' Untranslated Regions;abdominal aorta;Abdominal Aortic Aneurysm;Angiotensin II;Aorta;Autoimmune;Autoimmunity;Autophagocytosis;beta Aminopropionitrile;Binding;Binding Sites;Bone Marrow Transplantation;Cardiovascular Diseases;Cell Survival;Cells;Clinical;Cytoplasm;Death Rate;Deubiquitination;Development;Disease;Eligibility Determination;Event;experimental study;gene repression;Genes;Goals;Homeostasis;Human;hypercholesterolemia;in silico;In Situ Hybridization;Inflammation;Inflammatory;Infusion procedures;inhibitor;insight;Knowledge;Leukocytes;Low Density Lipoprotein Receptor;Medial;Mediating;Medical;MicroRNAs;mimetics;Modeling;monocyte;mortality;mouse model;Mus;new therapeutic target;novel;novel strategies;novel therapeutic intervention;Operative Surgical Procedures;Outcome;overexpression;Patients;Peptides;peripheral blood;pharmacologic;Plasma;posttranscriptional;pre-clinical;Prevalence;prevent;Prevention;Process;Protein-Lysine 6-Oxidase;Proteins;Recycling;Repression;Research;Role;Rupture;small hairpin RNA;Smooth Muscle Myocytes;Solid;Stress;TAF1 gene;TATA-Binding Protein Associated Factors;Testing;Therapeutic;therapeutic development;Tissues;Transcriptional Activation;transcriptome sequencing;treatment strategy;ubiquitin isopeptidase;Untranslated RNA;Vascular Smooth Muscle;Western Blotting

PROJECT_TITLE: Role of miR-146a in Abdominal Aortic Aneurysm

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


NIH_SPENDING_CATS: Genetics

ORG_DEPT: OPHTHALMOLOGY

PHR: Project Narrative Cells endure an almost constant assault of their genomes perpetrated by a host of environmental and endogenous stimuli including the oxidative stress, exposure to chemical agent, and faulty DNA synthesis. To counter such threats cells have evolved an elaborate system- collectively termed the DNA damage response - to sense DNA damage, signal its presence and mediate its repair. Recent studies in our laboratory have demonstrated that an enzyme - known as cGAS – recognized for its immune function alerts the cells of the DNA damage. Studies proposed in the application are focused on examining the molecular details of how this new DNA damage sensing system operates.

PI_NAMEs: KERUR, NAGARAJ  (contact)

PROGRAM_OFFICER_NAME: KELLY, HALONNA R

PROJECT_TERMS: Address;Adenosine Monophosphate;Affinity;Aging;Apical;assault;ataxia telangiectasia mutated protein;ATM activation;Binding;Biochemical;Biological Process;BRCA1 gene;Cell Aging;Cell Cycle;Cell Cycle Arrest;Cell Cycle Checkpoint;Cell Death;Cells;CHEK1 gene;CHEK2 gene;Chemical Agents;Chromatin;Complex;CRISPR/Cas technology;crosslink;Cyclic GMP;cytokine;Cytosol;Data;Defense Mechanisms;Dimerization;Dinucleoside Phosphates;Disulfides;DNA;DNA biosynthesis;DNA Damage;DNA Double Strand Break;DNA Repair;DNA strand break;Embryo;endodeoxyribonuclease SceI;endonuclease;Endoplasmic Reticulum;Enzymes;Eukaryotic Cell;Exposure to;Foundations;G1 Arrest;Generations;Genes;Genetic Transcription;Genome;genome integrity;Genomic DNA;Genomic Instability;Guanosine Triphosphate;Histones;Homeostasis;HTATIP gene;Human;IFNAR1 gene;immune function;Immune system;Immunologic Receptors;Inflammatory Response;insight;Interferon Type I;Interferons;Invertebrates;IRF3 gene;Laboratories;Left;Lymphocyte;Maintenance;Malignant Neoplasms;Manuscripts;Mediating;Mediator;Membrane Proteins;micronucleus;Mitotic;Molecular;Mus;Natural Immunity;Neoplasm Metastasis;novel;Oxidative Stress;Oysters;pathogen;Pathogen detection;Pathway interactions;Pattern recognition receptor;Periodicity;Process;receptor;recruit;repaired;response;Role;Sea Anemones;Second Messenger Systems;sensor;Signal Pathway;Signal Transduction;STAT2 gene;Stimulus;System;TANK-binding kinase 1;Telomerase;TP53 gene;tumorigenesis;V(D)J Recombination;Viral;Work

PROJECT_TITLE: Non-canonical cGAS signaling in DNA damage response

STUDY_SECTION: CSRS

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


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Genetics;Neurosciences;Orphan Drug;Radiation Oncology;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PROJECT NARRATIVE I will determine how glioblastoma, a deadly brain tumor, becomes resistant to radiation therapy. I will identify the mechanisms for this resistance in clinically relevant models of glioblastoma. This research may lead to the development of novel therapeutics to overcome radiation resistance in brain cancer by targeting novel molecular pathways.

PI_NAMEs: OSUKA, SATORU  (contact)

PROGRAM_OFFICER_NAME: SCHMIDT, MICHAEL K

PROJECT_TERMS: acute toxicity;Address;Adult;Brain;Brain Neoplasms;cancer cell;Candidate Disease Gene;career;Cell Cycle;Cell Death Signaling Process;cell growth;Cell Line;Cell Separation;Cell Survival;Cell-Cell Adhesion;Cells;chemotherapy;clinically relevant;CRISPR library;CRISPR/Cas technology;Data;Data Set;Databases;Development;DNA Damage;efficacy evaluation;Excision;Foundations;fractionated radiation;Future;Genes;Genetic Engineering;Genetic Heterogeneity;genome-wide;Glioblastoma;Glioma;Growth;Heparitin Sulfate;Human;IGF1 gene;In Vitro;in vivo;inhibitor;innovation;insight;Insulin-Like Growth Factor I;Insulin-Like-Growth Factor I Receptor;irradiation;Knock-out;Knowledge;Letters;Ligand Binding;Literature;Malignant Glioma;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;Mentors;Metabolic;Modeling;Molecular;mouse model;Mus;mutant;N-Cadherin;neoplastic cell;neuro-oncology;Neurosurgeon;novel;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;Outcome;overexpression;Pathway interactions;patient prognosis;Patient-Focused Outcomes;Patients;Phenotype;Play;Pre-Clinical Model;prevent;Property;Radiation;radiation resistance;Radiation therapy;Radiation Tolerance;Radiation-Sensitizing Agents;radioresistant;Radiosensitization;receptor;Receptor Activation;receptor expression;Receptor Signaling;receptor-mediated signaling;Recurrence;Recurrent tumor;Research;Research Personnel;Resistance;resistance mechanism;response;Role;screening;Secure;Signal Transduction;standard care;stem;stem cell population;stem cells;syndecan;Testing;The Cancer Genome Atlas;therapeutic target;therapy resistant;tumor;Western Blotting

PROJECT_TITLE: Targeting Adaptive Radioresistance of Glioblastoma


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: ARLINGTON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF TEXAS ARLINGTON

PHR: Research shows that many healthcare-associated infections (HAIs) can be indirectly transmitted via fomites, inanimate surfaces such as doorknobs, countertops, bedrails, and bedside tables, which are a common occurrence in the hospital setting. It has been demonstrated that fomites can harbor pathogenic microorganisms for extended periods of time, and that the most common disinfection methods are not totally effective since recontamination can occur at any moment after the application of disinfectants. Considering this, our long-term goal is to develop a nanocoating with sustained self-disinfecting capabilities activated by visible light to reduce fomite-mediated HAIs transmission.

PI_NAMEs: SOTO GARCIA, LUIS FERNANDO (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: absorption;Address;Adhesions;Adhesives;aged;Animal Model;Anions;Anti-Bacterial Agents;antimicrobial;Bacteria;bactericide;Biocide;Blood;Bodily secretions;Body Fluids;cell injury;Cell model;Development;Disinfectants;Disinfection;Dopamine;Drug Delivery Systems;Electrons;Environment;Epidemiology;Equipment;Escherichia coli;Formulation;Friends;fungus;Generations;Goals;Gram-Negative Bacteria;Hand;Health;Health Personnel;healthcare-associated infections;Hospitals;Human;Hydrogels;In Vitro;in vivo;Infection;Infection prevention;innovation;irradiation;Light;Lipids;Liquid substance;Manufacturer;Mechanics;Mediating;Medical;metal oxide;Methods;Microbe;microbial;microorganism;nanocoating;nanocomposite;nanomaterials;nanoparticle;Nanotechnology;novel;Nucleic Acids;oxidative damage;Oxidative Stress;Oxides;Oxygen;particle;pathogen;Pathogenicity;Patients;Performance;prevent;Prevention strategy;Property;Proteins;Public Health;Reaction;Reactive Oxygen Species;Recommendation;Research;Risk;Risk Reduction;Role;Route;Saliva;Sneezing;Source;Staphylococcus aureus;Superoxides;Surface;System;Testing;Time;Tissue Engineering;titanium dioxide;Touch sensation;translational potential;transmission process;Virus;Visible Radiation;Water;Work;wound healing

PROJECT_TITLE: A nanocoating for continuous disinfection of frequently touched surfaces

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


NIH_SPENDING_CATS: Dietary Supplements;Genetics;Nutrition

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative Despite its low abundance in the intestine, the enteroendocrine cell (EEC) controls important physiological processes like nutrient absorption, satiety, and systemic metabolism via production and secretion of enteroendocrine peptides (EEPs). This project will investigate the role of a G Protein-Coupled Receptor (GPCR) in the maintenance of intestinal lipid homeostasis through regulation of EEP activity in Drosophila. Findings will elucidate the connection between EEP expression and secretion pathways and potentially inform new therapeutic strategies for the treatment of metabolic disease.

PI_NAMEs: BARRAZA, DANIELA  (contact)

PROGRAM_OFFICER_NAME: BODDIE, THOMAS ARTIS

PROJECT_TERMS: Acetates;Antibiotics;Bypass;Calcium;Calcium Signaling;calmodulin-dependent protein kinase II;cardiovascular disorder risk;cell type;Cells;Data;detection of nutrient;Development;Diabetes Mellitus;Diet;Dietary Supplementation;differential expression;Drosophila genus;Drosophila melanogaster;Ecdysterone;Ensure;Enteroendocrine Cell;Exhibits;Exocytosis;Exocytosis Induction;experimental study;Fluorescence;Fluorescence Microscopy;fly;G-Protein-Coupled Receptors;Genes;genetic manipulation;Genetic Transcription;gut microbiota;Homeostasis;Imaging Techniques;Impairment;in vivo;innovation;Insecta;insight;interest;intestinal homeostasis;Intestines;ITPR1 gene;knock-down;Laboratory Finding;Ligands;Link;Lipids;Maintenance;Mediating;Metabolic Diseases;Metabolism;microbiota;model organism;Morbidity - disease rate;mortality;mutant;Mutation;neurotransmitter release;novel;novel therapeutic intervention;novel therapeutics;Nutrient;nutrient absorption;Obesity;Orphan;Outcome;overexpression;Pathway interactions;Peptide Synthesis;Peptides;Pharmaceutical Preparations;Phenotype;Physiological Processes;Predisposition;preservation;Process;Production;Public Health;Publishing;Quantitative Reverse Transcriptase PCR;Regulation;Regulatory Pathway;Reporting;Repression;response;Role;Satiation;Signal Pathway;Stains;steroid hormone;Stimulant;Stroke;Supplementation;Tachykinin;Testing;Therapeutic;treatment strategy;unpublished works;Visualization;Volatile Fatty Acids;Work

PROJECT_TITLE: Characterization of a G Protein-Coupled Receptor Implicated in Intestinal Lipid Homeostasis of Drosophila melanogaster.


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Eye Disease and Disorders of Vision;Hearing Loss;Neurosciences;Pediatric;Rehabilitation

ORG_CITY: BOYS TOWN

ORG_NAME: FATHER FLANAGAN'S BOYS' HOME

ORG_STATE: NE

PHR: PROJECT NARRATIVE  Vestibular loss can co-occur with hearing loss causing dual sensory deficits. This project examines vestibular loss as a contributing factor to reading difficulties for children with hearing loss, where previously only the effects of hearing loss and subsequent language difficulties have been considered. These results are expected to influence the identification and habilitation of vestibular loss in children with hearing loss.

PI_NAMEs: JANKY, KRISTEN L. (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: Activities of Daily Living;Address;Adult;Affect;Attention;Auditory;Child;Cochlear Implants;Cognition;Cognitive;Cognitive deficits;comorbidity;Comprehension;Development;executive function;Eye Movements;falls;Goals;Habilitation;Head;Head Movements;hearing impairment;Impairment;improved;Intervention;Language;language comprehension;large print;Letters;Linguistics;Link;literacy;Modeling;Neuroanatomy;normal hearing;Outcome;peer;Performance;phonology;Printing;Process;programs;Qi;Quality of life;Reading;reading ability;reading comprehension;reading difficulties;Rehabilitation therapy;Research;resilience;scaffold;Sensory;Severities;spatial memory;success;Testing;Theoretical model;Time;Training;Vestibular function;Vestibular loss;vestibular system;vestibulo-ocular reflex;Vision;Visual;Visual Acuity;visual tracking;Visuospatial;way finding;Work

PROJECT_TITLE: READING OUTCOMES IN CHILDREN WITH VESTIBULAR LOSS