NIH_SPENDING_CATS: Aging;Bioengineering;Breast Cancer;Cancer;Clinical Research;Dissemination and Implementation Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Women's Health Research

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: NARRATIVE The incidence of cancer and particularly that of breast cancer is rising in lower income countries; however, it is very difficult to provide diagnostic support to women with suspicious masses in resource-challenged areas. Obstacles include the absence of infrastructure needed to perform appropriate specimen histology as well as a lack of pathologists available to interpret the findings. In conjunction with a prominent breast-surgeon group in Ghana, we propose to develop an automated instrument into which needle biopsies of breast lesions can be introduced to immediately generate high-quality cellular-resolution images, including molecular phenotyping data, that can be used for diagnosis and treatment planning; the digital images can be interpreted locally, shared electronically, or even processed using artificial intelligence.

PI_NAMEs: LEVENSON, RICHARD M. (contact);SEIBEL, ERIC J;WIAFE, SETH ;WIAFE-ADDAI, BEATRICE

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Address;American;Area;Artificial Intelligence;artificial intelligence algorithm;Back;Breast;breast cancer diagnosis;breast lesion;Calibration;Caregivers;Caring;Centenarian;Cessation of life;Clinic;Clinical;Clinical Pathology;clinical translation;Collaborations;Computer software;Consultations;Core Biopsy;cost;Costs and Benefits;Country;Data;design;Detection;Development;Diagnosis;Diagnostic;Diagnostic Neoplasm Staging;digital;digital imaging;Disease Management;Engineering;Environment;ERBB2 gene;Evaluation;Evolution;experience;Feedback;Fees;Generations;Ghana;global health;Goals;Hand;Health Care Costs;histological specimens;Histology;Histopathology;Home;Hospitals;Image;imaging approach;imaging system;Immunofluorescence Immunologic;Immunohistochemistry;implementation evaluation;improved;Incidence;Income;Infrastructure;innovation;Institutional Review Boards;instrument;Intervention;Label;Laboratories;Logistics;Love;low and middle-income countries;low income country;Machine Learning;Malignant Breast Neoplasm;Malignant Neoplasms;Marketing;Mechanics;member;Methods;Molecular;molecular phenotype;Molecular Probes;Morphology;mortality;Needle biopsy procedure;Needles;opportunity cost;Optics;Pathologist;Pathology;Patient Recruitments;Patient Triage;Patients;peace;Performance;Peripheral;phenotypic data;Positioning Attribute;Procedures;Process;Protocols documentation;prototype;Reagent;research clinical testing;Resolution;Resources;Sampling;Services;Slide;Societies;success;Surgeon;System;Techniques;Technology;Testing;Time;tissue preparation;Tissues;tool;Training;treatment planning;Universities;usability;Validation;validation studies;Visit;Washington;Woman

PROJECT_TITLE: Breast core-needle diagnostics in LMICs via millifluidics and direct-to-digital imaging: development and validation in Ghana


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Clinical Research;Infectious Diseases

ORG_CITY: MAYWOOD

ORG_COUNTRY: UNITED STATES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_FIPS: US

ORG_NAME: LOYOLA UNIVERSITY CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The proposed training program provides mentored summer research opportunities for early-stage medical students with the goal of inspiring a passion for biomedical investigations. Through hands-on research training supplemented with didactic conferences on research and career development topics, we will introduce students to the excitement and challenges of research and encourage them to pursue careers that integrate research with clinical care.

PI_NAMEs: FITZGERALD, COLLEEN MARIE (contact)

PROGRAM_OFFICER_NAME: SASTALLA, INKA I

PROJECT_TERMS: Biomedical Research;career;career development;Chicago;clinical care;Clinical Research;Communicable Diseases;data management;Dedications;Development;Disease;Environment;Epidemiology;experience;Experimental Designs;Funding;Genetic;Goals;Immunology;Inflammation;Institution;medical schools;Medical Students;Mentors;Molecular;National Institute of Allergy and Infectious Disease;patient oriented;Process;Program Development;programs;Research;research and development;Research Project Grants;Research Training;responsible research conduct;skills;student training;Students;success;summer research;symposium;Training;Training Programs;Translational Research;Universities;Work

PROJECT_TITLE: Summer Research Experience for Medical Students in Inflammation and Infectious Diseases

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


ADMINISTERING_IC: MH

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: Project Narrative This highly integrated network of Investigators across 7 sites will continue to fill a significant gap in autism research by recruiting underserved subjects of self-reported African ancestry (African-Americans), a population that has not previously been well represented in ASD genetics. We will continue to grow genetic repositories and use comprehensive methods to find genes, while at the same time addressing health disparities by facilitating early diagnosis through our study to increase access to care.

PI_NAMEs: GESCHWIND, DANIEL H (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Address;admixture mapping;Adult;African American;African American population;African ancestry;Age;autism spectrum disorder;Behavior;Biological;Brain;burden of illness;Calendar;Child;Chromatin Structure;Chromosome abnormality;Clinical;clinical care;Code;Cognition;cohort;Collaborations;Color;Communities;Consensus;cost;Coupled;Data;data exchange;de novo mutation;Development;Developmental Gene;Diagnosis;Dideoxy Chain Termination DNA Sequencing;disorder risk;Disparity;Disparity in diagnosis;early detection biomarkers;Early Diagnosis;Etiology;European;Event;exome sequencing;Family;Family member;Frequencies;Future;gene discovery;Gene Expression Profiling;Gene Expression Regulation;gene network;Genes;Genetic;genetic analysis;genetic architecture;Genetic Diseases;Genetic Research;Genetic Risk;genetic risk factor;Genetic study;genetic testing;genetic variant;Genetic Variation;genome sequencing;genome-wide;genomic data;genomic locus;Genotype;Goals;health disparity;Health Services Accessibility;Heritability;Human;improved;improved outcome;insertion/deletion mutation;Internet;Interview;Investigation;Knowledge;Maps;member;Methods;Neurocognitive;Neurodevelopmental Disorder;novel;Outcome;Parents;Pathogenicity;Pathway Analysis;Pathway interactions;Patient Self-Report;Phase;Phenotype;Play;polygenic risk score;Population;Population Control;Population Heterogeneity;population stratification;Predisposition;proband;Quality of Care;Quantitative Trait Loci;Race;rare variant;Recording of previous events;recruit;Recurrence;remediation;repository;Research;Research Personnel;Resolution;Resources;Risk Factors;risk variant;RNA Splicing;Role;Sample Size;Sampling;School-Age Population;Services;Severities;Siblings;Single Nucleotide Polymorphism;Site;social;standard measure;Susceptibility Gene;Symptoms;Testing;Time;Toddler;transcriptome sequencing;transmission process;Untranslated RNA;Update;Validation;Variant;variant detection;Visual;visual tracking;whole genome;Work

PROJECT_TITLE: Autism Genetics Phase II: Increasing Representation of Human Diversity


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);American Indian or Alaska Native;Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Racial and Ethnic Minority Health Research;Rural Health

ORG_CITY: MINNEAPOLIS

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative Compared to the majority population, Indigenous rates of Alzheimer’s disease and related dementias (ADRD) are approximately 3 times higher, with a 10-year earlier onset, yet no culturally safe and accurate cognitive assessment tools exist for American Indian (AI) peoples. The American Indigenous Cognitive Assessment (AMICA) Project tackles this health disparity by adapting and validating a battery of 4 cognitive assessment tools (the AMICA battery) in 3 culturally distinct and diverse AI populations in Minnesota, Wisconsin, and New Mexico. Our research aims to develop a culturally safe cognitive assessment approach to provide accurate diagnoses, which in turn will help us achieve our long-term goal of improving the diagnosis and care of Indigenous persons with dementia across the ADRD continuum.

PI_NAMEs: GLEASON, CAREY E;JACKLIN, KRISTEN  (contact);PARKER, TASSY

PROGRAM_OFFICER_NAME: STOECKEL, LUKE

PROJECT_TERMS: Acceleration;accurate diagnosis;Activities of Daily Living;Address;Adult;Aging;Alzheimer disease detection;Alzheimer's disease related dementia;American Indian Population;American Indians;Area;Assessment tool;Australia;barrier to care;Canada;Caregivers;Caring;Clinical;clinical practice;cognitive interview;cognitive testing;Communities;community based participatory research;Congresses;Consensus;Cultural Backgrounds;Dementia;dementia care;Development;Diagnosis;Disparity;disparity reduction;early onset;Epidemiology;experience;Eye;Feedback;Goals;health disparity;Improve Access;improved;Indigenous;Indigenous American;Inequity;instrument;Interview;Knowledge;Letters;Measures;Mediation;member;Mental Depression;Methodology;Minnesota;Modification;Native-Born;neuropsychiatry;New Mexico;older adult;Outcome;Participant;Persons;Policies;Population;Practice Guidelines;Predictive Value;Procedures;Process;Property;Provider;Psychometrics;Pueblo Race;Reporting;Research;research clinical testing;Research Priority;Reservations;response;Risk;Running;Safety;Site;Specificity;standard of care;Surveys;Testing;Time;tool;tribal community;Tribal group;Tribes;United States;urban Native American;Wisconsin

PROJECT_TITLE: Addressing Alzheimer's Disease and Related Dementias Disparities: The American Indigenous Cognitive Assessment (AMICA) Project

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HDM-K(90)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences;Physical Injury - Accidents and Adverse Effects;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: PHILADELPHIA

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: PROJECT NARRATIVE Spinal cord injury (SCI) is a devastating condition that affects about 250,000 Americans with 17,700 new cases annually costing upwards of $2 million each for severe injuries. Leveraging Drexel’s Marion Murray Spinal Cord Research Center and its interactions and engagements across the university’s strong team of SCI experts. Drexel’s SCI Training Program contributes substantially to the training of new generations of researchers who shape the future of SCI research. T32 funding will enable this successful program to grow, training more exceptional young scientists in the field of SCI.

PI_NAMEs: BAAS, PETER W. (contact);COTE, MARIE-PASCALE

PROGRAM_OFFICER_NAME: WEIGAND, LETITIA ALEXIS

PROJECT_TERMS: innovation;Spinal cord injury;Training Programs

PROJECT_TITLE: Training Program on Innovative Approaches to Spinal Cord Injury


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome;Microbiome;Precision Medicine

ORG_CITY: SAN FRANCISCO

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Rigorous experiments from our lab and others have shown that human gut bacteria can metabolize numerous anticancer drugs; however, the major bacterial species that influence drug metabolism in patients, the genes and enzymes responsible, and the consequences for drug pharmaco-kinetics and -dynamics (PKPD) remain unknown. Here, we propose a series of in vitro and in vivo experiments to dissect the human gut bacterial species, genes, and enzymes responsible for the metabolism of the oral fluoropyrimidine capecitabine and their downstream consequences for drug PKPD in mice. Due to our focus on drugs used as current standard of care and naturally occurring bacterial species prevalent in the human gut microbiota, this preclinical research program is highly synergistic with ongoing clinical studies of cancer patients conducted by our team and the broader microbiome field.

PI_NAMEs: TURNBAUGH, PETER JAMES (contact)

PROGRAM_OFFICER_NAME: RASOOLY, AVRAHAM

PROJECT_TERMS: Accounting;Affect;Analytical Chemistry;Animal Model;Antimetabolites;Antineoplastic Agents;Bacteria;Bacterial Genes;bacterial genetics;bacterial resistance;Biochemical;Biological Assay;Biological Availability;Caenorhabditis elegans;cancer cell;Cancer Etiology;Cancer Model;Cancer Patient;cancer therapy;capecitabine;carcinogenesis;Cells;Cessation of life;Circulation;Clinical;Clinical Research;clinically relevant;colon cancer patients;Colorectal Cancer;colorectal cancer treatment;Coupled;Data;design;dietary supplements;Dihydropyrimidine Dehydrogenase;drug disposition;drug efficacy;Drug Kinetics;drug metabolism;Drug resistance;Drug usage;Enzymes;Escherichia coli;evidence base;experience;experimental study;fluoropyrimidine;Fluorouracil;Future;Genes;Genetic;Genotype;Gnotobiotic;Growth;gut bacteria;gut microbes;gut microbiome;gut microbiota;Hepatocyte;Homologous Gene;Human;Human Microbiome;Immunotherapy;Impairment;improved;In Vitro;in vivo;individual variation;individualized medicine;insight;inter-individual variation;Interdisciplinary Study;Intestines;Life;Malignant Neoplasms;Metabolic Biotransformation;Metabolic Pathway;Metabolism;metastatic colorectal;Methods;microbial;microbiome;mouse model;Mus;Mutagenesis;Operon;Oral;Oral Administration;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacology;Phenotype;Physiological;Positioning Attribute;pre-clinical;pre-clinical research;pressure;Prevalence;Prodrugs;programs;pyrimidine metabolism;Research;response;Role;Series;side effect;Source;standard of care;Study models;Taxon;Testing;Therapeutic;Therapeutic Effect;tool;Toxic effect;Treatment outcome;tumor metabolism;Vertebral column;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Metabolism of cancer chemotherapeutics by the human gut microbiome

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: INDIANAPOLIS

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Blood clots kill more humans than any other single pathogenic cause. Due to safety concerns and contraindications nearly 50% of patients that would benefit from acute thrombolytic therapy are not able to receive the current treatment due to a 5-10% rate of major bleeding, including intracranial hemorrhage. The proposed project will identify critical relationships that contribute to multivalent control of active enzymes in-vivo for the novel translation of direct fibrinolytic therapeutic interventions to digest blood clots with an improved safety profile.

PI_NAMEs: ALVES, NATHAN J (contact)

PROGRAM_OFFICER_NAME: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN

PROJECT_TERMS: active control;Active Sites;Acute;Address;Affect;Affinity;alpha 2-Glucoproteins;Alteplase;Antiplasmin;Avidity;Binding;Binding Proteins;Biological Assay;Blood coagulation;Blood Vessels;Bypass;Catheters;Characteristics;Clinic;clinical translation;Coagulation Process;Complex;Cytolysis;Data;Deep Vein Thrombosis;Diagnosis;Digestion;enzyme activity;Enzyme Inhibition;enzyme substrate;Enzyme-Linked Immunosorbent Assay;Enzymes;experimental study;Fibrin;Fibrinolysis;Fibrinolytic Agents;Future;genetic regulatory protein;Goals;Hemorrhage;Hemostatic function;Homo;Human;improved;In Vitro;in vivo;Infusion procedures;inhibitor;Injury;Intervention;Intracranial Hemorrhages;Ischemic Stroke;Knowledge;Kringles;Label;Lead;Length;limb ischemia;Link;Molecular;mouse model;Myocardial Infarction;nanoparticle;novel;novel strategies;Pathogenicity;Patients;Persons;Pharmacologic Substance;Plasmin;Plasmin Inhibitor;Plasminogen;Predictive Factor;Proteins;Pulmonary Embolism;Recurrence;Research;Risk;Safety;Scheme;Serpins;standard of care;Standardization;Surface;System;Therapeutic;Therapeutic Intervention;Thermodynamics;Thrombolytic Therapy;Time;Translating;translational potential;Translations;venous thromboembolism;Whole Blood

PROJECT_TITLE: Modulating Fibrinolysis Dynamics by Leveraging Multivalent Avidity to Control Enzyme Activity

STUDY_SECTION: HTBT

STUDY_SECTION_NAME: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PUBLIC NARRATIVE The brain is the archetypal electrical organ, but all organs have electrical signals, and many therapeutic drugs act by modulating these signals. This proposal describes a Training Program that is specifically geared to training scientists in this critical area.

PI_NAMEs: CHANDA, BARON ;NICHOLS, COLIN G (contact)

PROJECT_TERMS: Disease;Measures;Modeling

PROJECT_TITLE: TriMED: Measuring, Modeling and Manipulating Excitability and Disease


ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE For decades, the immune system and central nervous system were thought to operate independently one of another. Currently, it is clear that there is significant interaction between the immune system and brain, which is necessary to fight infections and support cognition, but is detrimental in numerous neuroinflammatory and neurodegenerative conditions. The Brain Immunology and Glia Training Program will provide a rich interdisciplinary training environment that leads to scientific breakthroughs and provides comprehensive training that will prepare trainees for careers in neuroimmunology and glia research.

PI_NAMEs: HARRIS, TAJIE H. (contact);KUCENAS, SARAH C

PROJECT_TITLE: Brain, Immunology and Glia Training Program


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Biotechnology;Genetic Testing;Genetics;Human Genome;Neurodegenerative;Neurosciences;Rare Diseases

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: Narrative: Leukodystrophies are a genetically heterogeneous disorders affecting the central nervous system white matter, or myelin. Although at least 240 genes have been associated with leukodystrophies, no formal gene curation has occurred and there is no formal structure to determine variant pathogenicity. This application proposes to develop and implement a leukodystrophy Expert Panel to perform as a Gene Curation Expert Panel and Variant Curation Expert Panel in accordance with ClinGen processes.

PI_NAMEs: VANDERVER, ADELINE LUCIE (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: accurate diagnosis;Advocacy;Advocate;Affect;Axon;Biochemical;Bioinformatics;Brain Diseases;brain magnetic resonance imaging;Central Nervous System;Childhood;Classification;clinical care;clinical decision-making;Clinical Research;clinical trial readiness;Clinical Trials;clinically actionable;ClinVar;Communities;Complex;Diagnosis;Diagnostic;diagnostic panel;Diagnostic tests;diagnostic tool;Disease;disease-causing mutation;Disputes;Documentation;emotional distress;Enrollment;Etiology;falls;Family;Funding;Future;Gene Frequency;Genes;Genetic;genetic counselor;genetic testing;genetic variant;Genomics;Goals;Grant;Guidelines;Hereditary Disease;improved;Knowledge;Laboratories;Lead;Leadership;leukodystrophy;Literature;Maintenance;member;Modification;Molecular;Morbidity - disease rate;mortality;Myelin;Natural History;Neonatal Screening;Neurologic;next generation sequencing;optimism;Outcome;Pathogenicity;Patients;Positioning Attribute;Procedures;Process;Publications;Rare Diseases;Recommendation;reproductive;Research Personnel;Resources;response;Role;Scientist;Standardization;Structure;System;Technology;Testing;Therapeutic;Training;Validation;Variant;white matter;Work

PROJECT_TITLE: GLIA-CTN Genomic Expert Curation Panel

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MGG-B(50)R]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Heart Disease;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: STANFORD

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVES LMNA-related dilated cardiomyopathy (LMNA-DCM) is one of the most prevalent forms of inherited heart disease. This study will investigate the molecular mechanisms of DCM by examining how crosstalk signaling among cardiomyocytes, endothelial cells, and cardiac fibroblasts via secreted proteins may contribute to the pathogenesis of LMNA-DCM. The proposed studies will provide insight into disease mechanisms and inform the development of new therapies that target intercellular signaling pathways in DCM.

PI_NAMEs: WONG, WING H.;WU, JOSEPH C. (contact)

PROGRAM_OFFICER_NAME: DESVIGNE-NICKENS, PATRICE

PROJECT_TERMS: 3-Dimensional;Affinity;Algorithms;aptamer;Base Pairing;Biological Assay;Calcium;candidate selection;Cardiac;Cardiac Myocytes;cardiac tissue engineering;Cardiovascular Diseases;Cell Communication;Cell Differentiation process;cell type;Cells;cellular targeting;Chemicals;Circulation;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Complement;coronary fibrosis;Defect;Development;Dilated Cardiomyopathy;Disease;drug candidate;druggable target;Electrophysiology (science);Endothelial Cells;endothelial dysfunction;Fibroblasts;Fibrosis;Fluorescence;Functional disorder;Funding;gain of function;Gel;Genes;Genome;genome editing;Heart;heart cell;Heart Diseases;Heart failure;high throughput screening;Human;human induced pluripotent stem cells;imaging system;improved;in vitro Model;Individual;induced pluripotent stem cell;induced pluripotent stem cell derived cardiomyocytes;Inherited;insight;intercellular communication;Investigation;Journals;Libraries;Ligands;loss of function;Maps;Medicine;Methods;Modality;Modeling;Molecular;Morphology;mutant;Mutation;Nature;new therapeutic target;novel therapeutic intervention;optical imaging;Organoids;Paper;Pathogenesis;Pathology;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Protein Secretion;Proteomics;Protocols documentation;Publications;Publishing;Qi;receptor;Reporter;Reporting;screening;Signal Pathway;Signal Transduction;single-cell RNA sequencing;stem cells;Technology;Tube;Variant;Ventricular;virtual;Wing

PROJECT_TITLE: Human iPSCs for Elucidating Intercellular Crosstalk Signaling in Dilated Cardiomyopathy

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


NIH_SPENDING_CATS: Cancer;Genetics;Kidney Disease;Orphan Drug;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: PROJECT NARRATIVE Cancer is the second leading cause of death in the United States. Translocation renal cell carcinoma (tRCC) is an aggressive kidney cancer without effective therapies and is an unmet medical need. This project explores how the antioxidant response may be a defining feature of, and therapeutic vulnerability in, tRCC.

PI_NAMEs: VISWANATHAN, SRINIVAS RAGHAVAN (contact)

PROGRAM_OFFICER_NAME: LIU, ZHIHUI

PROJECT_TERMS: 3-Dimensional;Antioxidants;Automobile Driving;Binding;Biochemical;Biology;Cause of Death;Cells;Chemicals;Chromatin;cohort;Collection;Complex;Credentialing;Data;Dependence;Disease;effective therapy;efficacy evaluation;Gene Family;Gene Fusion;Genes;Genetic;genetic approach;Genetic Transcription;genomic data;Genomics;Histologic;Histology;improved outcome;In Vitro;in vivo;in vivo Model;innovation;insight;Malignant Epithelial Cell;Malignant Neoplasms;Mediating;Medical;Molecular;Neoplasms;new therapeutic target;novel;novel therapeutic intervention;nuclear factor-erythroid 2;Oncogenic;Oxidation-Reduction;Oxidative Stress;Pathway interactions;Patient-Focused Outcomes;Play;posttranscriptional;pre-clinical;Prognosis;prospective;protein biomarkers;Proteomics;Regulation;Renal Carcinoma;Renal Cell Carcinoma;Reporting;response;Role;Signal Transduction;small molecule;standard of care;targeted treatment;Testing;TFE3 gene;Therapeutic;Therapeutic Agents;therapeutic target;transcription factor;Tumor Tissue;two-dimensional;United States;Work;Xenograft Model

PROJECT_TITLE: Molecular mechanisms and therapeutic targeting of activated NRF2 signaling in MiT/TFE translocation renal cell carcinoma

STUDY_SECTION: GRIC

STUDY_SECTION_NAME: Gene Regulation in Cancer Study Section[GRIC]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Aging;Biotechnology;Infectious Diseases

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Proteins embedded in cellular membranes carry out critical cellular activities important in health and disease, but to do so they must be properly inserted into the membrane, move to the right place in the cell, and have the appropriate membrane environment to function. Here, we will determine precisely at which step a protein called ZMPSTE24 acts on one such membrane protein IFITM3, helping it to achieve its activity in blocking virus host-cell fusion, the first step of viral infection. Insight into the mechanism whereby ZMPSTE24 enables IFITM3 to attain its function could have general applicability to other membrane proteins and may someday be harnessed to develop an antiviral drug.

PI_NAMEs: MICHAELIS, SUSAN D. (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Anti-viral Agents;antiviral drug development;Biogenesis;Biological;Biology;biophysical properties;Cell fusion;Cell membrane;Cells;Cellular Membrane;COVID-19 pandemic;Cytoprotection;Defect;Disease;Endoplasmic Reticulum;Ensure;Environment;farnesylation;fluidity;Goals;Health;Human;IFITM1 gene;Infection;insight;Integral Membrane Protein;Interferons;Laboratories;Lamin Type A;Lead;Lipid Bilayers;Longevity;Longitudinal Studies;Membrane;membrane activity;Membrane Lipids;Membrane Proteins;Metalloproteases;Mus;novel;Nuclear Matrix-Associated Proteins;overexpression;Pathway interactions;Peptide Hydrolases;Positioning Attribute;Post-Translational Protein Processing;prelamin A;Premature aging syndrome;Progeria;Property;Proteins;Proteolytic Processing;Proteome;Quality Control;recruit;Research;Role;trafficking;Viral;Viral Physiology;Virus;Virus Diseases;Zinc

PROJECT_TITLE: Role of the integral membrane protease ZMPSTE24 in membrane protein biogenesis and virus-host cell fusion


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: Information from spectral CT on tissue composition helps with clinical diagnosis and treatment. Current spectral CT methods involve difficult hardware changes and have limited material differentiation capabilities. Support for this proposal will provide a practical, low cost spectral CT solution for multi-material differentiation.

PI_NAMEs: XU, JINGYAN  (contact)

PROGRAM_OFFICER_NAME: TORNAI, MARTIN PAUL

PROJECT_TERMS: Abdomen;Affect;Algorithms;cardiac vasculature;Clinical;clinical application;clinical diagnosis;clinical implementation;Clinical Pathways;clinical translation;Clinical Treatment;computational platform;contrast imaging;cost;Data;data acquisition;data exchange;Dedications;density;design;detector;Development;Elements;Engineering;Evaluation Studies;experience;fabrication;Foundations;Future;Generations;Goals;Image;imaging platform;improved;interest;Investigation;Maps;Measures;Methods;Modeling;Patients;Performance;Phase;Photons;prevent;Process;Property;prototype;Qualifying;Radiation Dose Unit;research clinical testing;response;Roentgen Rays;Rotation;Scanning;Shapes;Source;System;Techniques;Thick;Thinness;Time;Tissues;Tube;voltage;Work;X-Ray Computed Tomography

PROJECT_TITLE: Stationary spectral encoding for multi-energy CT with energy-integrated detectors

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Arthritis;Bioengineering;Brain Disorders;Chronic Pain;Nanotechnology;Neurosciences;Opioids;Osteoarthritis;Pain Research;Physical Injury - Accidents and Adverse Effects;Prescription Drug Misuse;Substance Misuse

ORG_CITY: OMAHA

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: NARRATIVE While many alternative analgesics have been used clinically, opioids are still the mainstay analgesic for peri- surgical musculoskeletal pain management. Given the current opioid epidemic, there is an urgent need for the development of potent and non-addictive analgesics. In this proposal, we seek to further develop and optimize a novel opioid prodrug formulation (ProGel-HMP) that provides potent local analgesia for musculoskeletal pain with minimal adverse opioid side effects and a low risk of developing dependency and addiction.

PI_NAMEs: WANG, DONG  (contact)

PROGRAM_OFFICER_NAME: MARQUITZ, ARON

PROJECT_TERMS: Absence of pain sensation;Acute Pain;addiction;Address;Analgesics;aqueous;Behavior;Benchmarking;Biodistribution;Blood;Bone callus;bone fracture repair;Brain;candidate selection;Cell Physiology;Cells;Chronic;chronic pain;Circulation;Clinical;clinical practice;Closed Fractures;copolymer;Data;Degenerative polyarthritis;Dependence;design;Development;Dimensions;Drug Addiction;Drug Kinetics;efficacy evaluation;efficacy testing;Experimental Models;Femoral Fractures;Formulation;Functional disorder;Gel;Glucocorticoids;Hydrogels;Hydromorphone;In Vitro;in vivo;in vivo optical imaging;Inflammation;Inflammatory;injury and repair;Kidney;Kinetics;Liquid substance;Mechanics;Medial meniscus structure;Mediating;Medication Management;methacrylamide;Modeling;Modification;Molecular Weight;mouse model;Mus;Musculoskeletal;Musculoskeletal Diseases;musculoskeletal injury;Musculoskeletal Pain;nanomedicine;Non-Steroidal Anti-Inflammatory Agents;novel;Operative Surgical Procedures;Opiate Addiction;Opioid;opioid epidemic;opioid mortality;optical imaging;Orthopedics;osteoarthritis pain;Pain;Pain management;pain relief;Pathology;Phagocytes;Phase Transition;Physiological;Physiology;Postoperative Pain;Postoperative Period;Prodrugs;Property;repaired;Risk;Safety;safety assessment;Series;side effect;Site;skeletal;skeletal injury;Spinal Cord;Surgeon;Surgical Specialties;Surveys;Testing;Time;Tissues;Translations;Trauma;Traumatic Arthropathy;Weight

PROJECT_TITLE: Nonaddictive opioid prodrug nanomedicine for musculoskeletal pain

STUDY_SECTION: NANO

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


ED_INST_TYPE: SCHOOLS OF SOCIAL WELFARE/WORK

NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Injury;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Mental Illness;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Suicide;Suicide Prevention

ORG_CITY: CHARLOTTE

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF NORTH CAROLINA CHARLOTTE

ORG_STATE: NC

PHR: PROJECT NARRATIVE Current suicide prevention and interventions efforts are not sufficient to decrease suicide risk in Black youth and Black LGBTQ+SGL youth. The overarching goal of this mixed-methods study is to pilot test a novel care coordination intervention aimed to improve risk detection, service referrals, treatment, continuity of care, and service engagement among Black youth and Black LGBTQ+SGL youth ages 14-17. This study will inform feasibility of a scalable trial for a future R01 study, which will have the potential to improve suicide care practices, reduce disparities, and prevent suicide-related outcomes for diverse Black youth.

PI_NAMEs: GRYGLEWICZ, KIM ;KARVER, MARC STUART;RICHARDSON, SONYIA COPELAND (contact);VANCE, MICHELLE M

PROGRAM_OFFICER_NAME: MARRO, MARY ACRI

PROJECT_TERMS: access disparities;Address;Age;arm;Behavior;Black race;care coordination;care outcomes;Caregivers;Caring;Cause of Death;Clinical;Communities;community based participatory research;Continuity of Patient Care;County;culturally appropriate intervention;Detection;Development;disparity reduction;Elements;Eligibility Determination;empowerment;Ethnic Population;experience;Faith;Faith-based organization;Family;Family Relationship;Feasibility Studies;Feedback;Feeling suicidal;Focus Groups;follow-up;Future;Goals;Health;Health behavior;Health Services Accessibility;help-seeking behavior;high risk;implementation strategy;improved;Individual;Infrastructure;Intervention;Interview;Investigation;Lesbian Gay Bisexual Transgender Queer;Linguistics;Link;Location;Measures;Mental Health;Mental Health Services;Methods;minority communities;Modeling;Monitor;Motivation;National Institute of Mental Health;non-suicidal self injury;North Carolina;novel;Outcome;Outcome Assessment;Perception;Phase;phase 1 study;pilot test;Population;Predisposition;primary outcome;Problem Solving;Process;Protocols documentation;Provider;Psychiatric therapeutic procedure;Questionnaires;racial population;Randomized;Randomized, Controlled Trials;Recommendation;Recording of previous events;recruit;Reduce health disparities;reducing suicide;referral services;Resources;Risk;Risk Behaviors;Safety;screening;Screening procedure;Self-Injurious Behavior;service delivery;service engagement;service utilization;Services;Single-Blind Study;skills;suicidal behavior;suicidal risk;Suicide;Suicide attempt;Suicide prevention;suicide rate;Symptoms;system-level barriers;Teenagers;theories;Therapeutic;therapy design;treatment adherence;treatment as usual;uptake;usability;Youth

PROJECT_TITLE: CA-LINC: A Culturally Adapted Care Coordination Suicide Detection and Intervention Model for Black Youth


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Polymyxins are last-resort antibiotics that are used to treat multi-drug resistant infections, but incidence of resistance to polymyxins is growing, and the alterations that cause it are poorly understood in mechanistic terms. In many bacterial species, enzymatic modification of Lipid A, a common lipid that decorates their outer membrane, enables the development of resistance to polymyxins and other cationic antimicrobial peptides. The goal of this research program is to investigate the molecular mechanisms responsible for the development of polymyxin resistance in atomic detail, using advanced structural biology techniques, which will lead to a mechanistic understanding of the underlying enzymatic reactions and in the future inform the design of therapeutic compounds capable of preventing or reversing resistance to polymyxin antibiotics.

PI_NAMEs: PETROU, VASILEIOS I (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Anabolism;anti-microbial drug;anti-microbial peptide;Antibiotic Resistance;Antibiotics;Antimicrobial Cationic Peptides;Antimicrobial Resistance;Bacteria;bacterial genetics;Binding;Biochemical Reaction;Biological Assay;Catalysis;Chemicals;cofactor;Cryoelectron Microscopy;design;Development;Drug Design;Electrostatics;Endotoxins;enzyme pathway;enzyme structure;Enzymes;Escherichia coli;experience;Future;glycosyltransferase;Goals;Gram-Negative Bacteria;Gram-Negative Bacterial Infections;Growth;Health;Human;Incidence;Infection;Innate Immune System;inorganic phosphate;insight;Lipid A;Lipids;Lipopolysaccharides;Membrane;Membrane Proteins;Metals;Modification;Molecular;Multi-Drug Resistance;multidisciplinary;Mutagenesis;novel therapeutics;Pathway interactions;Polymyxin Resistance;Polymyxins;Predisposition;prevent;programs;Protein Biochemistry;Proteins;Pseudomonas aeruginosa;Research;Resistance;Resistance development;Salmonella enterica;structural biology;Structure;Techniques;Therapeutic;Training

PROJECT_TITLE: Structure and mechanism of membrane enzymes responsible for bacterial lipid modification and polymyxin resistance

STUDY_SECTION: MRAB

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurosciences;Opioid Misuse and Addiction;Opioids;Pediatric;Prevention;Social Determinants of Health;Substance Misuse

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: Project Narrative Various adverse and protective environments may affect child development. The Healthy Brain and Child Development National Consortium (HBCD-NC) will follow 7,500 mothers and their children from 24 locations across the U.S. from before birth to 10 years of age to better understand which harmful and protective environments exert the greatest impact on child development. This study will help to improve the health and development of children across the nation.

PI_NAMEs: DAPRETTO, MIRELLA ;GAO, WEI  (contact);GREGORY, KIMBERLY D;SMITH, LYNNE M.

PROGRAM_OFFICER_NAME: PRABHAKAR, JANANI

PROJECT_TERMS: 10 year old;Address;Adverse event;Affect;Alcohols;Behavioral;Biological;Birth;Brain;Caregivers;caregiving;Child;child bearing;Child Development;cohort;Communities;Conceptions;COVID-19;critical period;Data;Data Collection;Data Coordinating Center;data integrity;Data Set;data standards;design;Development;DNA;early experience;early life exposure;Electroencephalography;Enrollment;Environment;Environmental Exposure;Environmental Hazards;Epigenetic Process;Ethics;Ethnic Origin;Event;experience;Exposure to;Feedback;General Population;Genes;Goals;hazard;Health;Helping to End Addiction Long-term;Human;improved;Infant;Infection;innovation;insight;Life;Link;Location;Magnetic Resonance Imaging;Malnutrition;maltreatment;Marijuana;Maternal Health;maternal stress;Measures;Methods;Modality;Monitor;Mothers;multidimensional data;multimodality;neurodevelopment;neuroimaging;Newborn Infant;novel;Opiate Addiction;Opioid;opioid misuse;Outcome;Participant;Persons;Physiological;Population;postnatal;Pregnancy;pregnant;Pregnant Women;prenatal;prenatal exposure;Process;protective factors;Protocols documentation;psychologic;Psychopathology;Public Health;Public Policy;Race;recruit;remote assessment;Research;Research Design;Research Personnel;Sampling;Second Pregnancy Trimester;Severities;Shapes;Site;socioeconomics;sound;Speed;stem;Stress;Structural Racism;substance use;Time;Time Study;Tobacco;tool;Toxicant exposure;Training;United States;United States National Institutes of Health;Woman;Work

PROJECT_TITLE: 1/24 Healthy Brain and Child Development National Consortium

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-D(51)R]


ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE In addition to uncovering novel strategies to treat infections, studies of how cells defend against invading viruses can lead to the discovery of fundamental cellular mechanisms as well as new principles relevant to vaccine design and the treatment of autoimmune diseases. To identify new pages in the playbook of infection, we interrogate the biology of genes lacking known functions which have genetic signatures characteristic of factors that determine infection outcomes, such as key antiviral proteins. Our framework has already revealed an ancient cellular circuit, which is targeted by viruses, linked to the regulation and production of energy.

PI_NAMEs: HANCKS, DUSTIN  (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Autoimmune Diseases;Bioinformatics;Biological;biological adaptation to stress;Biological Assay;Biology;Cell Physiology;Cells;Characteristics;Cicatrix;Conflict (Psychology);Databases;Dimensions;Electron Transport;Evolution;experimental analysis;Gene Combinations;gene discovery;gene function;gene product;Genes;genetic signature;Genomics;Host Defense;Host Defense Mechanism;Hypoxia;Immune response;Infection;innovation;Invaded;Link;MicroRNAs;Mitochondria;Modeling;Molecular;Molecular Profiling;novel;novel strategies;Organelles;Outcome;Poxviridae;Production;programs;Recording of previous events;Regulation;Research;RNA Viruses;Signal Transduction;Stress;System;Textbooks;TP53 gene;Vaccine Design;Vaccinia;Vesicular stomatitis Indiana virus;Viral;Viral Proteins;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Evolution-guided Studies of Mitochondrial Functions

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


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Data Science;Gene Therapy;Genetics;Networking and Information Technology R&D (NITRD)

ORG_CITY: Columbus

ORG_NAME: MASSMATRIX, INC.

ORG_STATE: OH

PHR: PROJECT NARRATIVE Accelerating Gene Therapy and Editing with Advanced MS-Based Data Analysis for Nonstandard and Hybrid Nucleotide Sequences The project seeks to speed up and improve reliability in the development of life-saving and life-enhancing, precision, oligonucleotide (short RNA or DNA molecules) therapeutics and magnify the positive impact of biomedical research and life science education worldwide. Due to manual intervention in a critical, mass spectrometry data analysis pipeline, progress in the development, quality assurance and manufacturing of these therapeutics is bottlenecked and compromised. Through novel data analysis workflow methods and a modern cloud experience for analyzing and validating experimental data, the project is expected to improve the accuracy and reliability of results and alleviate the bottleneck, thereby deepening understanding of biological systems and improving resource allocation through better decision making, including saving lives via improved drug safety, efficacy and availability.

PI_NAMEs: JOHNSON, GEORGE HALL (contact)

PROGRAM_OFFICER_NAME: BILLINGSLEA, EDDIE

PROJECT_TERMS: Acceleration;Address;Adherence;Algorithms;application programming interface;base;Base Sequence;Biological Assay;Biological Sciences;biological systems;biomarker identification;Biomedical Research;blind;Client;cloud platform;Collaborations;commercialization;Communities;Computer software;Data;data access;Data Analyses;data analysis pipeline;Data Element;data integration;data management;data repository;Data Science;data sharing;data visualization;Decision Making;design;Development;Disease;Disparate;DNA;Drug Industry;Education;experience;Feedback;flexibility;Future;gene therapy;Genes;Grant;Growth;Hybrids;improved;Industry;Intervention;Ions;Knowledge;Life;Lipids;Machine Learning;Manuals;manufacture;Marketing;Mass Spectrum Analysis;medication safety;member;Methods;Modeling;Modernization;Modification;Molecular;Monitor;Mutation;Mutation Analysis;next generation sequencing;novel;Occupations;oligonucleotide therapeutics;Oligonucleotides;Pathway interactions;Peptides;Phase;Principal Component Analysis;Process;prototype;quality assurance;Quality Control;quantum;Reliability of Results;Reproducibility;Research;Resolution;Resource Allocation;Resources;RNA;science education;Scientist;Sequence Alignment;Specific qualifier value;Speed;Standardization;sugar;System;tandem mass spectrometry;Testing;Therapeutic;transcriptome sequencing;Update;Vendor;Visualization;web portal;web services


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

PHR: Project Narrative In high-risk industries, such as aviation, voluntary incident reporting is a widely used and effective technique through which frontline personnel describe events—particularly near misses—that serve as early warnings of safety problems. Incident reporting systems have existed in U.S. hospitals for over 50 years, but they have not been as effective at improving patient safety. This cluster randomized controlled trial will test whether a novel intervention, the Safety Action Feedback and Engagement (SAFE) Loop, enhances incident reporting practices, improves nurses’ perceptions of incident reporting, and lowers rates of high-priority medication events, as compared with using an existing incident reporting system.

PI_NAMEs: NUCKOLS, TERYL  (contact)

PROGRAM_OFFICER_NAME: HAUGSTETTER, MONIKA

PROJECT_TITLE: A Cluster Randomized Controlled Trial Comparing the Safety Action Feedback and Engagement (SAFE) Loop with an Established Incident Reporting System

STUDY_SECTION: HSQR

STUDY_SECTION_NAME: Healthcare Patient Safety and Quality Improvement Research[HSQR]


NIH_SPENDING_CATS: Aging;Genetics;Human Genome;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Project Narrative  Over an organism’s lifetime skin stem cells (SCs) lose their vigor or diminish in numbers which manifests into aging-related phenotypes that include epidermal atrophy, fragility, hair loss disorders, and delayed wound healing but the fundamental mechanisms driving SC aging in the adult skin remain largely unknown. In this project, I will investigate the functional role of age-dependent changes in transcriptional and chromatin landscape implicated in promoting SC aging. This work will pave the way for future line of research which will seek to address how epigenetic regulated processes impact epidermal aging, which in turn will provide new scientific avenues for translational research application in the treatment for aging-associated conditions and disorders.

PI_NAMEs: FLORA, POOJA  (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: Address;Adult;Age;age related;age related changes;age related decline;aged;Aging;aging process;aging related;Architecture;Atrophic;Automobile Driving;base;Biochemical;cell age;cell community;Cell Count;Cell model;cell type;Chromatin;Cleavage Under Targets and Release Using Nuclease;Code;Complex;Control Animal;Curiosities;Cutaneous;Disease;epidermal stem cell;Epidermis;Epigenetic Process;epigenetic regulation;Epithelium;Equilibrium;Failure;Foundations;Future;gene repression;Genetic Models;Genetic study;Genetic Transcription;genome-wide analysis;Goals;Growth;Hair;Hair follicle structure;histone methylation;histone modification;Homeostasis;Human;Immunofluorescence Immunologic;Impaired wound healing;In Vitro;in vivo;Injury;insight;Intrinsic factor;Invertebrates;Knowledge;Light;Longevity;loss of function;Malignant Neoplasms;Mediating;Methods;Methyltransferase;Molecular;multiple omics;novel;old mice;Organism;Phase;Phenotype;Polycomb;PRC1 Protein;premature;preservation;pro-aging;Process;programs;regeneration potential;Regenerative capacity;Regulation;Regulator Genes;Repression;Research;Research Personnel;Role;self-renewal;senescence;Skin;Skin Aging;stem cell aging;stem cell differentiation;stem cell exhaustion;stem cell self renewal;stem cells;Stratified Epithelium;Stratum Basale;Structure;Testing;Thinness;Tissues;Translational Research;Work;wound healing

PROJECT_TITLE: Identifying epigenetic factors in control of epidermal stem cell longevity in the adult skin

STUDY_SECTION: AMS

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


ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: Project narrative The number of follicular helper T cells (Tfh) correlates with disease severity in lupus patients, and reducing the number of Tfh cells in mouse models eliminates disease. This proposal investigates the factors that are responsible for the increased number of Tfh cells in lupus. We propose that a better understanding of these factors may identify targets that can be used for their elimination, and provide a safe therapeutic approach.

PI_NAMEs: MOREL, LAURENCE  (contact);ZADEH, MANSOUR M

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Affect;Affinity;Autoantibodies;Automobile Driving;autoreactivity;B-Lymphocyte Subsets;B-Lymphocytes;BLR1 gene;C57BL/6 Mouse;CD4 Positive T Lymphocytes;Cell Differentiation process;Cell Physiology;Cells;cohort;congenic;Congenic Mice;Cues;Data;Diet;dietary manipulation;Disease;Disease Outcome;Drug or chemical Tissue Distribution;Environmental Impact;Environmental Risk Factor;Exhibits;experimental study;fecal microbiota;follow-up;Frequencies;Genes;Genetic;Genetic Determinism;genetic signature;Genome;Germ-Free;Glucose;Glutamine;Glycolysis Inhibition;gut dysbiosis;gut microbiota;Health;Helper-Inducer T-Lymphocyte;Human;Immunoglobulin A;Immunoglobulin Class Switching;improved;in vitro Assay;in vivo;innovation;interleukin-21;Investigation;ITGAX gene;Knowledge;Lupus;lupus prone mice;Metabolic;Metabolic Pathway;Metabolism;metabolome;metabolomics;microbial;microbiome;Modeling;Molecular;mouse model;Mus;Norleucine;novel;Outcome;pathogenic autoantibodies;Pathway interactions;Patients;Peripheral;Production;programmed cell death protein 1;Reagent;response;Severities;Severity of illness;SLEB1 gene;SLEB3 gene;solute;Sorting;Spleen;Susceptibility Gene;synergism;Systemic Lupus Erythematosus;T-Lymphocyte Subsets;Testing;Therapeutic;transcriptome;transcriptome sequencing;transcriptomics;Tryptophan;Tryptophan Metabolism Pathway;Validation;Variant

PROJECT_TITLE: Determinants of follicular helper T cell expansion in lupus

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-T(02)]


NIH_SPENDING_CATS: Biomedical Imaging;Cardiovascular;Clinical Research;Heart Disease

PHR: Project Narrative: Atrial fibrillation (Afib) is a common arrhythmia that is currently difficult to manage. Afib ablation is more effective than medical therapy for keeping patients in normal rhythm, but failure is common due to an inability to create properly placed, permanent ablation lesions. This proposal translates an MRI method we have developed for seeing permanent ablation lesions to 1) detect sites of incomplete Afib ablation and 2) guide completed Afib ablation.

PI_NAMEs: KOLANDAIVELU, ARAVINDAN  (contact)

PROGRAM_OFFICER_NAME: DANTHI, NARASIMHAN

PROJECT_TERMS: 3-Dimensional;Ablation;Acute;Animal Model;Animals;Arrhythmia;Atrial Fibrillation;Atrial Flutter;Cardiac ablation;Chronic;Clinical;contrast enhanced;Contrast Media;cooking;Edema;effective therapy;Failure;Feedback;follow-up;healing;Health Care Costs;Heart;Heart Atrium;Histologic;Histology;Iatrogenesis;Image;imaging modality;improved;improved outcome;Injury;Intravenous;Lesion;Location;Magnetic Resonance Imaging;Measures;Medical;Methods;Morbidity - disease rate;Myocardium;Necrosis;necrotic tissue;Operative Surgical Procedures;Outcome;Patients;porcine model;Procedures;Pulmonary veins;Radiofrequency Interstitial Ablation;Recurrence;Reporting;Site;soft tissue;success;Symptoms;Techniques;Thinness;Time;tissue injury;Tissues;Translating;Treatment Efficacy;Treatment Failure;Ventricular Tachycardia;Visualization

PROJECT_TITLE: Atrial fibrillation ablation assessment and guidance using native-contrast T1 weighted MRI

STUDY_SECTION: IGIS

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


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Neurodegenerative

PHR: The Johns Hopkins University (JHU) Trial Innovation Center (TIC) represents an established, high functioning team of multisite trial PIs, experienced trial scientists, project managers, statisticians, and trial staff, including external trialist collaborators from 5 CTSA Hubs, that will leverage operational services and trial science in CTSA trials to develop and study novel operational innovations that improve participant engagement, protocol compliance and measurement of trial endpoints. The team will demonstrate that TIC innovations in trial design, execution, and evaluation can lead to better trial performance, including faster start-up, faster completion, greater intervention adherence and more precise endpoints leading to enhanced efficiency and impact. The JHU TIC will build capacity by disseminating results of valid CTSA-TIN innovations tested within consortium trials to CTSA clinical trial teams and research trainees.

PI_NAMEs: HANLEY, DANIEL F (contact)

PROGRAM_OFFICER_NAME: BURWEN, DALE R

PROJECT_TERMS: Adherence;Case Study;Clinical;Clinical and Translational Science Awards;Clinical Trials;Collaborations;Communities;Consensus;Consultations;Data;data quality;Dissemination and Implementation;Educational Curriculum;Effectiveness;effectiveness evaluation;Enrollment;Evaluation;evidence base;experience;follow-up;Funding;Goals;Human Resources;improved;Individual;Informatics;innovation;Intervention;Joints;Laboratories;Lead;Link;Measurement;Measures;Methods;Mission;Multi-Institutional Clinical Trial;multi-site trial;Multicenter Trials;Multiple Partners;National Center for Advancing Translational Sciences;Needs Assessment;novel;operation;Outcome;patient engagement;Patients;Performance;performance site;Preceptorship;Principal Investigator;Process;Production;program dissemination;programs;Protocol Compliance;Protocols documentation;randomized trial;randomized, clinical trials;Randomized, Controlled Trials;recruit;Research;Sampling;Science;Scientist;service delivery;Services;Site;Speed;Testing;Time;timeline;tool;Training;Translational Research;trial design;trial planning;Universities;uptake;Validation;Visit;Work

PROJECT_TITLE: Johns Hopkins University Trial Innovation Center


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);Bioengineering;Biomedical Imaging;Brain Disorders;Cerebrovascular;Data Science;Dementia;Machine Learning and Artificial Intelligence;Neurodegenerative;Neurosciences;Precision Medicine;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE: This application proposes to map cellular and molecular alterations associated with normal aging and Alzheimer’s disease in brain tissue using imaging mass spectrometry in tandem with various forms of microscopy, multiomic spatial profiling, and machine learning. We hypothesize that comprehensive multimodal molecular imaging and analysis of brain tissues will provide a deeper mechanistic understanding of understudied neuropathologies, contributing to the complexity and heterogeneity of Alzheimer’s disease, including cerebral amyloid angiopathy (CAA), dystrophic neurites, neuropil threads, granulovacuolar degenerating bodies, and gliosis . This work will generate high spatial resolution and comprehensive molecular atlases of normal aging and Alzheimer’s human brains and our advanced data analysis strategies will further reveal disease state/transition/class-specific molecular signatures, provide insight into key molecular pathways along with changes or disruption across tissue regions of interest, and identify potential disease subgroups.

PI_NAMEs: ROBINSON, RENA A. S.;SCHRAG, MATTHEW ;SPRAGGINS, JEFFREY M (contact)

PROGRAM_OFFICER_NAME: YANG, AUSTIN JYAN-YU

PROJECT_TERMS: Academic Medical Centers;Aging;Alzheimer's Disease;Alzheimer's disease brain;Amyloid beta-Protein;Analytical Chemistry;Anterior;Architecture;arteriole;Astrocytes;Atlases;Autophagosome;Axon;Biochemistry;biocomputing;Biogenesis;Biology;Blood capillaries;Brain;Brain Mapping;brain tissue;cell type;Cellular biology;Cerebral Amyloid Angiopathy;Cerebral hemisphere hemorrhage;Cerebrum;Clinical;comparative;Complement;Computer Analysis;Computer Vision Systems;Computers and Advanced Instrumentation;Data;Data Analyses;Data Science;Data Set;Deposition;Development;Disease;disease heterogeneity;Disease Marker;disorder subtype;drivers of aging;effective therapy;Environment;Epidemic;experience;Eye;Frustration;genetic architecture;Glean;Gliosis;Goals;Heterogeneity;Hippocampus;Histology;Human;human tissue;hyperphosphorylated tau;Image;image registration;imaging facilities;imaging modality;imaging platform;Impaired cognition;improved;Infrastructure;innovation;insight;interest;Investigational Therapies;Kidney;Laboratories;Lesion;Link;lipidome;lipidomics;Lipids;Lobe;Lysosomes;Machine Learning;Maps;mass spectrometric imaging;Mass Spectrum Analysis;Membrane;metabolome;meter;Methodological Studies;Methodology;Microanatomy;Microglia;Microscopy;Modality;Molecular;Molecular Analysis;molecular imaging;molecular marker;Molecular Profiling;mouse model;Multimodal Imaging;multimodality;Multiomic Data;multiple omics;Multivariate Analysis;Neurites;Neurofibrillary Tangles;Neurology;Neurons;neuropathology;Neuropil Threads;normal aging;novel therapeutic intervention;older patient;Organelles;Pancreas;Parietal Lobe;Pathologic;Pathology;Pathway interactions;patient population;Performance;Process;Proteins;Proteome;Proteomics;Protocols documentation;Regional Anatomy;Research;Research Personnel;Resolution;Resources;Senile Plaques;Source;Spatial Distribution;Superior temporal gyrus;supervised learning;Systems Biology;Technology;Tissues;tool;transcriptome;transcriptomics;Universities;Validation;Vascular Diseases;Work

PROJECT_TITLE: Elucidating Molecular Drivers of Aging and Alzheimer's Disease via Multimodal Imaging Mass Spectrometry


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

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: RELEVANCE Through an interdisciplinary team this proposal will generate single-cell type nomenclatures of brain regions of interest involved in persistent HIV and chronic opioid exposure. A combination of innovative single-cell RNA sequencing tools, proximity and spatial mapping studies and computational analysis will reveal cell-type specific molecular rearrangements and synergistic interactions of HIV and opioids.

PI_NAMEs: MILNER, TERESA A;NDHLOVU, LISHOMWA C;TILGNER, HAGEN ULRICH (contact)

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Affect;Animals;antiretroviral therapy;Area;Association Learning;Astrocytes;Autopsy;Behavior assessment;Biological Process;Brain;brain cell;brain health;Brain region;cell type;Cells;Characteristics;Chromatin;Chronic;Cognitive;Computer Analysis;Computing Methodologies;Data;Data Set;Detection;Dimensions;Drug Exposure;epigenome;epigenomics;Event;Exons;experimental study;Exposure to;Functional disorder;Future;Gene Expression;Generations;Genes;Genetic Transcription;genome-wide;Goals;Health;Hippocampus;HIV;HIV Infections;Human;Infection;innovation;interest;Knowledge;Learning;Literature;Maps;Methods;Microglia;Modality;Modeling;Molecular;molecular rearrangement;Monitor;Neuroglia;Neurons;neuropathology;Nomenclature;nonhuman primate;novel;Opioid;opioid exposure;Opioid Peptide;Opioid Receptor;opioid use disorder;Oxycodone;Persons;pharmacologic;Phenotype;Poly(A)+ RNA;Prefrontal Cortex;Process;programs;Protein Isoforms;Publishing;Regimen;Reporting;Resolution;response;Rodent;sequencing platform;sex;Signaling Molecule;simian human immunodeficiency virus;single cell ATAC-seq;single cell genomics;single cell sequencing;single-cell RNA sequencing;Site;Slice;Slide;Stress;Tissues;tool;transcriptome;transcriptome sequencing;transcriptomics;Viral;Work

PROJECT_TITLE: Integrative Single Cell isoform and chromatin accessibility Mapping of Chronic Opioid Exposure in Cognitive Brain Areas in HIV


NIH_SPENDING_CATS: Biotechnology;Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Gene Therapy;Genetics;Hepatitis;Liver Cancer;Liver Disease;Rare Diseases

ORG_DEPT: PEDIATRICS

PHR: The non-coding lnc122/miRNA122 gene locus is responsible for limiting some RNAi therapeutic approaches in the liver. We will further study the mechanism and how high concentrations of RNAi transcripts interfere with this gene locus as well as its molecular function.

PI_NAMEs: KAY, MARK A (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: 3' Untranslated Regions;Acute;acute toxicity;Address;adenovirus mediated delivery;Affect;Biological Assay;Biology;Cell Physiology;Cells;cellular targeting;Cessation of life;Chromatin;Chromatin Structure;Chronic;Clinical Trials;conditional knockout;design;differential expression;Disease;Enzymes;Epigenetic Process;Exclusion;FDA approved;Feedback;Gene Expression;Gene Expression Profiling;Gene Expression Regulation;Gene Transfer;Genes;Genetic;Genetic Diseases;Genetic Transcription;genomic locus;Germ Lines;Goals;Grant;Hepatitis B Virus;Hepatitis C virus;Hepatocyte;hepatoma cell;Hepatotoxicity;Homeostasis;Human;Implant;improved;in vivo;Individual;Infection;insight;knock-down;Knock-out;knockout animal;Knockout Mice;Learning;lipid metabolism;Liver;liver cancer model;Liver diseases;Liver Failure;Liver Fibrosis;Liver neoplasms;Liver Regeneration;Long-Term Effects;Mammals;Maps;Methods;MicroRNAs;Modeling;Molecular;Monitor;Morbidity - disease rate;mortality;Mus;Mutation;nonalcoholic steatohepatitis;novel;Nuclear;oligonucleotide therapeutics;Outcome;overexpression;Pathologic;Patients;permissiveness;Phenotype;Poly A;Primary carcinoma of the liver cells;Process;promoter;Protein Isoforms;Regenerative capacity;Regulation;response;RNA;RNA Interference;RNA Interference Therapy;RNA Precursors;RNA Splicing;Role;short hairpin RNA delivery;small hairpin RNA;Small RNA;Source;Testing;Therapeutic;Tissues;Toxic effect;Transcript;Transgenes;tumor;tumor growth;Tumor Suppressor Proteins;Untranslated RNA;Variant;vector;Viral hepatitis;Virus Diseases;virus genetics;Work;Xenograft Model

PROJECT_TITLE: Acute/chronic limitations to transcriptional RNAi therapies for infectious and other liver diseases

STUDY_SECTION: TAG

STUDY_SECTION_NAME: Therapeutic Approaches to Genetic Diseases Study Section[TAG]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Vector-Borne Diseases;West Nile Virus

PHR: NARRATIVE: This application seeks to identify the initial cellular targets for WNV infection in the periphery using a human lymphoid tissue explant system and an immunocompetent mouse model. Our studies will provide a comprehensive view of the landscape of cells that become initially infected in humans and how this may contribute to pathogenesis and neuroinvasion.

PI_NAMEs: LIM, JEAN KYOU (contact)

PROJECT_TERMS: Arbovirus Encephalitis;Architecture;Bite;Blood;CD4 Positive T Lymphocytes;Cell Lineage;Cell surface;cell type;Cells;cellular targeting;Central Nervous System;chemokine;Collecting Cell;Culicidae;cytokine;Data;Dendritic Cells;Deposition;Development;draining lymph node;Engineering;Enterobacteria phage P1 Cre recombinase;Event;Flow Cytometry;Gastrointestinal tract structure;Genome;Germ Cells;Hematopoietic;Human;human pathogen;Immune response;Immunocompetent;Immunophenotyping;In Situ Hybridization;In Vitro;in vivo;in vivo Model;Individual;Infection;Injections;keratinocyte;Label;lymph nodes;Lymphoid;Lymphoid Cell;Lymphoid Tissue;Macrophage;MicroRNAs;Modeling;monocyte;mouse model;Mus;mutant;Myelogenous;Myeloid Cells;Neurons;neutrophil;Organ;Pathogenesis;Peripheral;Phenotype;Physiological;Population;Primary Cell Cultures;Production;RNA;single-cell RNA sequencing;Site;Skin;Spleen;Stains;System;T-Lymphocyte Subsets;Target Populations;Testing;Time;Tissue Model;transmission process;United States;Vaccines;Viral;Viral Pathogenesis;Viremia;Virulent;Virus;Virus Replication;Visualization;West Nile viral infection;West Nile virus;Wild Type Mouse

PROJECT_TITLE: Identification of the initial cells infected by West Nile virus ex vivo and in vivo

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIA-S(02)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Digestive Diseases;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Inflammatory Bowel Disease;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: CORAL GABLES

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE Inflammatory bowel diseases (IBD) are immune-mediated diseases whose downstream consequences include surgery and cancer, leading to medical disability and a high economic and social burden in the US. Although traditionally thought of as a disease affecting Caucasians of European descent, a rising number of Hispanics, both foreign-born and first-generation Hispanic-Americans, are developing IBD. In this proposal, we will dramatically increase the breadth of the Hispanic genetic sample collection in the US paired with careful phenotyping to make discoveries on the pathogenesis of IBD through novel, high-resolution genetic and genomic approaches.

PI_NAMEs: ABREU, MARIA TERESA (contact);MCCAULEY, JACOB L

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Admixture;Affect;African American;Age;Age of Onset;Alleles;American;ATAC-seq;Biological;Black Populations;Caucasians;Cells;Characteristics;Chromatin;Chronic;Clinical;Clinical Trials;cohort;Collection;Colon;Communities;Country;County;Crohn's disease;Data;Databases;Dedications;Dendritic Cells;Development;Diet;disability;Disease;disease phenotype;Disparity;Economics;Environment;Environmental Exposure;Epigenetic Process;Europe;European;European ancestry;Florida;Functional disorder;gene environment interaction;Gene Expression;Generations;Genes;Genetic;genetic approach;genetic architecture;Genetic Diseases;Genetic Predisposition to Disease;Genetic Research;Genetic Risk;Genetic Structures;Genetic study;Genetic Variation;Genome;genome wide association study;Genomic approach;genomic locus;Genomics;Genotype;Goals;Grant;Hispanic;Hispanic Americans;hispanic community;Hispanic Populations;ileum;Immigrant;Immigration;Immune;Immune response;Immune System Diseases;Immunologics;improved;Incidence;Individual;Industrialization;Inflammation;Inflammatory Bowel Diseases;interest;intergenerational;Intestines;Knowledge;Latin America;Latin American;Latinx;Linkage Disequilibrium;Location;Macrophage;Malignant Neoplasms;Maps;Measures;Mediating;Medical;Methods;microbiome;Modification;Mucosal Immune System;Mucositis;Mucous Membrane;multiple omics;National Institute of Diabetes and Digestive and Kidney Diseases;neutrophil;North America;Not Hispanic or Latino;novel;Operative Surgical Procedures;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Pattern;Phagocytes;Pharmaceutical Preparations;Phenotype;Population;Prevention;Property;Publishing;recruit;Research;Resolution;response;Risk;risk variant;Role;sample collection;Sentinel;Severities;social;social health determinants;Susceptibility Gene;Texas;transcriptome sequencing;transcriptomics;Ulcerative Colitis;Universities;Work

PROJECT_TITLE: University of Miami IBD Genetic Research Center: Understanding the Genetic Architecture of IBD in the LatinX Community


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases;Kidney Disease;Rare Diseases

ORG_NAME: TUFTS UNIVERSITY BOSTON

PHR: Enterohemorrhagic E. coli (EHEC) causes ~265,000 cases of human intestinal and systemic illness in the U.S. annually, but there are no specific treatments for the deadly kidney disease caused by spread of a toxin from the gut to the bloodstream. We are studying how the toxin may move around the body in tiny sacs that 1) contain other substances that enhance the toxin’s effects on kidney cells, and 2) can hide the toxin hide from antibody treatments. Our long-term goal is to use knowledge gained to develop treatments to prevent potentially the fatal kidney disease resulting from EHEC infection.

PI_NAMEs: KAILASAN VANAJA, SIVAPRIYA ;LEONG, JOHN M (contact);RATHINAM, VIJAY ;THORPE, CHELESTE M

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: Affect;Animal Experiments;Animal Model;Animals;Antibiotics;Antibody Therapy;Apoptosis;Bacteriophages;beef;Binding;biological adaptation to stress;Blood;Blood Cells;Blood Circulation;Blood Platelets;Cell Communication;cell injury;Cell model;cell type;Cells;Childhood;Circulation;Coculture Techniques;Colon;Complement;cytokine;Cytosol;cytotoxicity;Data;Development;Diarrhea;diarrheal disease;Disease;Distal;druggable target;efficacy testing;Electron Microscopy;Endoplasmic Reticulum;endoplasmic reticulum stress;Epithelium;Erythrocytes;Escherichia coli EHEC;Escherichia coli Infections;Escherichia coli O157:H7;Event;Exposure to;extracellular vesicles;Fibrin;Flagellin;Flow Cytometry;foodborne;Future;Generations;globotriaosylceramide;glomerular endothelium;Glycolipids;Goals;gut colonization;gut inflammation;Hemolytic Anemia;Hemolytic-Uremic Syndrome;Hemorrhagic colitis;holotoxins;Human;Image;In Vitro;in vivo;Infection;Infiltration;Inflammasome;Inflammatory;Ingestion;Injury;Intestinal Absorption;intestinal epithelium;Intestines;Intoxication;intraperitoneal;Kidney;kidney cell;Kidney Diseases;Kidney Failure;Knowledge;Life;Macrophage;Mammalian Cell;MAP Kinase Kinase Kinase;Measures;Mediating;Mediator;Membrane;microvesicles;Modality;Modeling;Molecular;monocyte;mouse model;Mus;mutant;nanoparticle;neural;neutrophil;novel therapeutics;Organ;Oryctolagus cuniculus;particle;pathogen;Pathogenesis;Patients;Pattern;pharmacologic;Phase;podocyte;Predisposition;prevent;Production;Protein Synthesis Inhibitors;Publishing;renal damage;Renal Tissue;response;Ribosomes;Role;Serotyping;Shiga Toxin;Supportive care;synergism;Systemic disease;Thrombocytopenia;thrombotic;Thrombus;TLR4 gene;Toxin;transmission process;Tubular formation;uptake;Uremia;Vascular Endothelium;Vesicle;Virulence Factors;Western Blotting;Work

PROJECT_TITLE: Outer Membrane Vesicles in Shiga Toxin-Mediated Inflammatory and Thrombotic Responses Leading to Systemic Disease

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Bioengineering;Biomedical Imaging;Cancer;Lung;Rare Diseases

ORG_CITY: DENVER

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF DENVER (COLORADO SEMINARY)

ORG_STATE: CO

PHR: Narrative. Magnetic resonance imaging with nitroxide radicals will define the redox status of a tumor microenvironment and lung damage in a mouse, permit selection of individuals who would benefit from targeted cancer and respiratory therapies, and monitor treatment efficacy. The benchtop imager will make technology for measuring redox status and local oxygen concentration available to biotechnology companies and academic labs that are developing new frontiers in cancer therapies.

PI_NAMEs: EATON, GARETH R (contact)

PROGRAM_OFFICER_NAME: GRODZINSKI, PIOTR

PROJECT_TERMS: Acute Lung Injury;Acute Respiratory Distress Syndrome;Animals;Biology;Biomedical Research;Biotechnology;Bite;Bleomycin;Blood Vessels;Brain Injuries;Budgets;cancer therapy;carcinogenesis;Chemotherapy and/or radiation;Chicago;Code;commercialization;Computer software;Data;data acquisition;design;design and construction;Development;Disease;Disease Progression;Drug Industry;Electron Spin Resonance Spectroscopy;Engineering;Equilibrium;Evaluation;experience;experimental study;Feedback;Floor;Free Radicals;frontier;Functional disorder;Generations;Glutathione;Goals;Grant;high risk;Image;Image Enhancement;image reconstruction;imager;imaging modality;improved;in vivo;in vivo imaging;in vivo monitoring;Individual;Industrialization;Industry;Inflammation;Inflammatory;innovation;Kinetics;Knowledge;Laboratories;Link;Lung Diseases;lung injury;magnetic field;Magnetic Resonance Imaging;Malignant Neoplasms;manufacturability;Measurement;Measures;Mediating;Medical;Medical center;member;Methods;microwave electromagnetic radiation;Mitochondria;Modality;Modeling;Molecular;Monitor;Mus;Myocardial Infarction;Myopathy;Nerve Degeneration;nitroxyl;Noise;Oxidation-Reduction;Oxidative Stress;Oxygen;Oxygen saturation measurement;Pathology;Penetration;Performance;Peripheral;Persons;Physiologic pulse;Physiological;Power Sources;pre-clinical;preclinical imaging;Process;Property;prototype;Pulse Oximetry;Radiation therapy;Reaction;Reactive Oxygen Species;reconstruction;Relaxation;Reproducibility;Resolution;Respiratory Therapy;Role;Scanning;Severities;Signal Transduction;software systems;Source;Specific qualifier value;Spectrum Analysis;Speed;Spin Trapping;Stroke;Students;success;Superoxides;Surface;System;targeted cancer therapy;Techniques;Technology;Testing;Time;Tissues;Training;Trauma;Treatment Efficacy;treatment response;tumor;tumor microenvironment;Tumor Pathology;Universities;Viscosity;Work;wound healing;Writing

PROJECT_TITLE: Preclinical Electron Paramagnetic Resonance Tumor Imager


NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: Project Narrative Viruses continue to shape human history through disease, but modified viruses are used as vaccines. The study of viruses has become a source of knowledge: unifying scientific principles are discovered through virology. The Virology and Gene Therapy track forms trainees into rigorous scientists and innovators who further develop the science of virology while also leveraging it to prevent and treat cancer and genetic diseases.

PI_NAMEs: CATTANEO, ROBERTO B. (contact)

PROGRAM_OFFICER_NAME: SASTALLA, INKA I

PROJECT_TERMS: Doctor of Philosophy;gene therapy;Training Programs;virology

PROJECT_TITLE: PhD Training Program in Virology and Gene Therapy

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Advisory Committee[MID]


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: These experiments study V(D)J recombination, an essential genetic process that occasionally makes mistakes and generates aberrations in human chromosomes during the development of white blood cells known as lymphocytes. These aberrations contribute to the development blood cancers such as lymphoma and leukemia and it is hoped that this work will provide insights into how V(D)J recombination works and thereby into the causes of these mistakes and methods by which they could be prevented.

PI_NAMEs: SCHATZ, DAVID G. (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: Adaptive Immune System;Address;Alleles;antagonist;Antigen Receptors;B-Cell Development;Binding;Biochemical;Black Box;Cell Nucleolus;Cell Nucleus;Cell Physiology;Cellular biology;Chromatin;Chromosomal translocation;Chromosome Deletion;cohesin;Complex;Cryo-electron tomography;Cryoelectron Microscopy;Data;Development;Dissection;DNA;endonuclease;Enzymes;Equilibrium;Exclusion;experimental study;Funding;Genes;genetic approach;Genetic Processes;Genetic Recombination;Genome;Genome Stability;genomic locus;Goals;Hematopoietic Neoplasms;Histone Code;Histones;Human Chromosomes;Image;Immunoglobulins;In Situ;In Vitro;in vivo;insight;J segment gene;Knowledge;Label;leukemia/lymphoma;Leukocytes;Lymphocyte;Maps;Mediating;Methods;Modification;Molecular;Mus;Mutagenesis;Mutant Strains Mice;Mutate;Mutation Analysis;N-terminal;novel;Nuclear;Nucleosome Core Particle;Nucleosomes;particle;Peptide Signal Sequences;Peptides;Physiological;Play;Positioning Attribute;prevent;Proteomics;Rag1 Mouse;Reaction;Reader;Receptor Gene;recombinase;recruit;Regulation;Research Personnel;Rest;RNA Processing;Role;Scanning;Series;Signal Transduction;Structure;superresolution microscopy;T-Cell Lymphoma;T-Cell Receptor;Tail;Testing;trafficking;V(D)J Recombination;virtual;Work;X-Ray Crystallography

PROJECT_TITLE: Mechanism and Regulation of V(D)J Recombination

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_NAME: DANA-FARBER CANCER INST

PHR: Narrative Accurate identification of genes and transcripts in the human genome and their structural and functional annotation is a fundamental requirement for high quality analysis of data informing both genome biology and clinical genomics. Gene annotation accuracy is critical, as incorrect and incomplete information will impact downstream analyses and introduce potentially significant false positive and false negative errors; for example, despite significant advances in genetic testing, supported by improvements in DNA sequencing technologies, many patients do not receive a genetic diagnosis possibly due to the incompleteness of the ‘representation’ of these gene sequences (gene annotation). To overcome these obstacles, it is imperative that systematic efforts be undertaken to develop a comprehensive catalogue or reference set of fully experimentally verified human full- length protein-coding transcripts.

PI_NAMEs: HILL, DAVID E.;MARTIN, FERGAL JAMES;VIDAL, MARC  (contact)

PROGRAM_OFFICER_NAME: GILCHRIST, DANIEL A

PROJECT_TERMS: Alternative Splicing;analysis pipeline;Apoptotic;Automated Annotation;Base Sequence;BCL2L1 gene;Biology;biotypes;Catalogs;cell type;Cells;Clinical;Code;Collaborations;Collection;Complement;Complementary DNA;Complex;Computer software;Data;Data Analyses;data archive;Data Set;Databases;Deposition;Development;Dimensions;Disease;DNA sequencing;Exhibits;experimental study;Expressed Sequence Tags;follow-up;Genes;genetic disorder diagnosis;genetic testing;Genetic Transcription;Genome;genome-wide;Genomics;Goals;Human;Human Genome;improved;insight;International;Investigation;Knowledge;Length;Literature;Manuals;Messenger RNA;Methods;Modeling;molecular sequence database;Nature;Open Reading Frames;Paper;Patients;Post-Translational Protein Processing;Process;Protein Isoforms;Proteins;Proteome;Resources;response;RNA Splicing;Sensitivity and Specificity;Specificity;Stimulus;Structure;Technology;Time;Tissues;Transcript;transcriptome;transcriptome sequencing;Translations;whole genome

PROJECT_TITLE: Generating a full-length reference transcriptome for human protein-coding genes

STUDY_SECTION: GNOM

STUDY_SECTION_NAME: Genome Research Study Section[GNOM-G]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Depression;Machine Learning and Artificial Intelligence;Mental Health;Mental Illness;Pediatric;Prevention;Serious Mental Illness;Social Determinants of Health

ORG_CITY: ISLAMABAD

ORG_COUNTRY: PAKISTAN

ORG_FIPS: PK

ORG_NAME: SHIFA TAMEER-E-MILLAT UNIVERSITY

PHR: Project narrative The SMART-STEP study will use Sequential Multiple Assignment Randomized Trial (SMART) design as a practical way to evaluate the effectiveness of a stepped care package to treat the symptoms of CMDs in adolescents studying in low resource public school settings of Pakistan. SMART-STEP will drive forward the knowledge and understanding of teachers delivered Enhanced School Mental Health Program (eSMHP) and Cognitive Behavioral Therapy (CBT) based STARS (Sustainable Technology for Adolescent to Reduce Stress) self-help chat-bot by matching these intervention strategies with symptoms and functioning of the adolescents resulting in optimized treatment outcomes for adolescents with CMDs. This will allow optimized mental health care to be delivered to adolescents within the school settings that will not only improve their wellbeing and functioning but also result in their improved academic performance.

PI_NAMEs: HAMDANI, SYED USMAN  (contact)

PROGRAM_OFFICER_NAME: CAMPBELL-ROSEN, HOLLY RENEE

PROJECT_TERMS: Address;Adolescent;adolescent mental health;Adopted;adverse outcome;Advisory Committees;aged;Anxiety;anxiety management;behavior test;Behavioral;career development;Caring;chatbot;child depression;clinical outcome measures;cognitive testing;Cognitive Therapy;common symptom;Communities;Computers;cost;cost effective;cost-effectiveness evaluation;Counseling;Country;COVID-19 pandemic;Data;Decision Trees;depressive symptoms;design;Development;Development Plans;dosage;Early identification;Economics;effective intervention;Effectiveness;effectiveness evaluation;Effectiveness of Interventions;effectiveness testing;Emotional;Ensure;evidence base;experience;feasibility testing;Guidelines;Health;health literacy;Heterogeneity;Human;improved;Income;Intervention;Knowledge;Life;Lived experience;Low income;Measures;Mediator;Mediterranean Region;Mental Depression;Mental disorders;Mental Health;mental health policy;Mental health promotion;Mental Health Services;National Institute of Mental Health;optimal treatments;Pakistan;Parents;Patient Self-Report;Patients;Performance;Personal Satisfaction;Persons;Phase;Prevalence;Problem Solving;programs;psychoeducation;psychologic;psychological distress;Psychosocial Assessment and Care;Questionnaires;Recommendation;recruit;reduce symptoms;relapse prevention;Reporting;Research;Research Personnel;Resources;response;scale up;school health;Schools;self help;Sequential Multiple Assignment Randomized Trial;Site;skills;Specialist;Specific qualifier value;Stress;stress management;stress reduction;Subgroup;success;symptom treatment;symptomatic improvement;Symptoms;System;teacher;Teacher Professional Development;Technology;Therapeutic;Thinking;Time;Training;Training Programs;treatment as usual;treatment optimization;Treatment outcome;trial design;Well in self;Work;World Health Organization;Youth

PROJECT_TITLE: School based stepped care TrEatment for adolescent depression in Pakistan- a Sequential Multiple Assignment Randomized Trial (SMART-STEP)


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

ORG_CITY: DAVIS

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: Project narrative Fear and anxiety underlie the most common forms of mental illness in the United States, with more than 30% of Americans experiencing an emotional disorder at some point in their life. Consequently, a major goal of NIH is to understand the neural mechanisms that underlie adaptive and maladaptive threat processing. The hippocampus and locus coeruleus both contribute to fear and anxiety, but it is not known how they interact during these states to promote the encoding of aversive memories. This represents a major gap in our understanding of the neural systems that contribute to emotional disorders. Altered catecholamine release by the locus coeruleus accompanies schizophrenia, bipolar disorder, and ADHD, which are often comorbid with fear and anxiety disorders. Alzheimer’s disease also produces severe atrophy of the locus coeruleus, which reduces catecholamine release throughout the brain and is thought to exacerbate amnesia. To determine how altered catecholamine levels impact these disorders, it is essential to establish the basic mechanisms by which neuromodulatory inputs to the hippocampus regulate the formation of aversive memories.

PI_NAMEs: WILTGEN, BRIAN J (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Address;Alzheimer's Disease;American;Amnesia;Animals;Anxiety;Anxiety Disorders;Association Learning;Atrophic;Attention deficit hyperactivity disorder;Auditory;aversive conditioning;Aversive Stimulus;Bipolar Disorder;Brain;Catecholamines;comorbidity;conditioned fear;Cues;Data;Disease;Dopamine;Dopamine Antagonists;Dopamine Receptor;Dorsal;Electrophysiology (science);Emotional disorder;emotional experience;Environment;Event;experience;experimental study;Extinction;follow-up;Food;Fright;Future;Genetic;Goals;Hippocampus;Hour;Human;Impairment;in vivo;Learning;Life;locus ceruleus structure;long term memory;member;Memory;memory consolidation;Memory impairment;memory process;Mental disorders;Monitor;neural;neuromechanism;Neuromodulator Receptors;Neurons;neuroregulation;Norepinephrine;novel;optogenetics;Play;prevent;Procedures;Process;psychologic;Rattus;rehearsal;response;Role;Schizophrenia;sensor;Shock;Stimulus;Synaptic plasticity;System;Testing;Time;tool;Training;United States;United States National Institutes of Health

PROJECT_TITLE: The role of novelty and surprise in aversive conditioning

STUDY_SECTION: BRLE

STUDY_SECTION_NAME: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Autoimmune Disease;Genetics;Human Genome;Lupus;Women's Health Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Females are biased to develop the autoimmune disease lupus, suggesting a genetic basis in the X-chromosome, which is enriched for immunity-related genes. We will investigate the molecular mechanisms specific to female B cells that regulate gene expression on the inactive X chromosome, and how alterations with these pathways impair B cell function and increase lupus disease severity in mice. Our findings will reveal genes predisposed to epigenetic alterations and aberrant expression for female-biased lupus disease.

PI_NAMEs: ANGUERA, MONTSERRAT C (contact)

PROJECT_TERMS: Alleles;Antibody Formation;Autoantibodies;Autoantigens;Autoimmune;Autoimmune Diseases;Autoimmunity;autosome;B cell differentiation;B-Cell Activation;B-Lymphocyte Subsets;B-Lymphocytes;Binding;Binding Proteins;Biological Assay;biological sex;Biotinylation;bisulfite sequencing;Cell Physiology;cellular imaging;ChIP-seq;Chromatin;Chronic;cohesin;cohesion;Complex;Data;Disease;Disproportionately impacts women;DNA;DNA Methylation;Dosage Compensation (Genetics);ds-DNA;Epigenetic Process;Exhibits;Female;Functional disorder;Gene Dosage;Gene Expression;Gene Modified;gene repression;Gene Silencing;Genes;Genetic;Genetic Transcription;Goals;Hypermethylation;Immune;Immunity;Impairment;In Vitro;in vivo;Inflammation;innovation;insight;Interferon Type I;Interferons;Link;Lupus;Lupus erythematosus cell;lupus-like;Lymphocyte;Maintenance;male;Mediating;Methylation;Modification;Molecular;mouse model;Mus;novel;Nuclear Lamina;Nuclear Matrix-Associated Proteins;Oligonucleotides;overexpression;Pathway interactions;Patients;Predisposing Factor;preservation;Pristane;Process;Production;promoter;Protein Methylation;Proteins;Publishing;Regulator Genes;response;RNA;RNA Binding;Role;SAFB gene;Severity of illness;Signal Transduction;Somatic Cell;Susceptibility Gene;Systemic Lupus Erythematosus;Testing;Therapeutic Intervention;Transcript;whole genome;Work;X Chromosome;X Inactivation

PROJECT_TITLE: Role for nuclear matrix proteins and DNA methylation for XCI maintenance in female lymphocytes


NIH_SPENDING_CATS: Biotechnology;Cancer;Immunotherapy;Neuroblastoma;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Radiation Oncology;Rare Diseases;Skin Cancer

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative  To improve adoptive T cell therapy for patients with solid tumors, we propose to use targeted radionuclide therapy (TRT) to condition the patient prior to receiving T cells. Our TRT consists of 67Cu-LLP2A that can 1) selectively deplete the patient’s systemic lymphocytes and make space for adoptive T cells; 2) eliminate immune cells including suppressive cells within the tumor to ensure the better function of adoptive T cells; 3) target tumor cells and reduce overall tumor burden through direct cytotoxic effects. Altogether, with the benefit of more efficacy than conventional conditioning agents, 67Cu-LLP2A TRT has the potential to redefine current approaches for adoptive T cell therapy and improve the outcomes in patients with cancer.

PI_NAMEs: PATEL, RAVI BHASKER (contact)

PROGRAM_OFFICER_NAME: CAPALA, JACEK

PROJECT_TERMS: A/J Mouse;Adoptive Cell Transfers;Adoptive Immunotherapy;Adult;Affinity;Behavior Therapy;Binding;Biodistribution;Cell Death Induction;cell killing;Cell Lineage;Cells;Cellular immunotherapy;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;chemotherapy;Childhood;chimeric antigen receptor;chimeric antigen receptor T cells;conditioning;cost;CRISPR/Cas technology;Cyclophosphamide;cytotoxic;Disease remission;Dose;dosimetry;early phase clinical trial;Engraftment;Ensure;Failure;fludarabine;Future;Image;Immune;immune clearance;Immunotherapy;improved;improved outcome;In Vitro;in vivo;Infusion procedures;Integrin alpha4beta1;Label;leukemia;Lymphocyte;Malignant Neoplasms;Measures;Mediating;Melanoma;Modeling;Mus;Myelogenous;neoplastic cell;Neural Crest Cell;Neuroblastoma;novel;Organ;Patient-Focused Outcomes;Patients;Penetration;peptidomimetics;Phenotype;pre-clinical;preclinical study;preconditioning;Proliferating;Radiation;radiation risk;Radionuclide therapy;Refractory;Regimen;risk mitigation;single photon emission computed tomography;Site;small molecule;Solid Neoplasm;success;T cell therapy;T-Lymphocyte;Testing;Tissues;Toxic effect;transcriptome;Translations;tumor;Tumor Burden;tumor microenvironment;Validation;Whole-Body Irradiation;X-Ray Computed Tomography

PROJECT_TITLE: VLA-4–targeted 67Cu-LLP2A preconditioning enhances efficacy of T-cell-based adoptive immunotherapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CTH-S(02)M]


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);Biotechnology;Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetics;Neurodegenerative;Neurosciences

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: NARRATIVE Alzheimer's disease (AD) and tauopathies are the most common types of dementia in the elderly. Clinically they are characterized by memory loss and impairment of cognitive functions secondary to a progressive accumulation in the brain of toxic tau protein. Currently, because the mechanisms responsible for this accumulation remain unknown, no therapy is available against these devastating diseases. In recent years, small molecules called microRNAs have emerged as master regulators of brain health and disease. Although their levels are altered in AD and tauopathies, we still do not know whether they are responsible for them. Our research program will test the hypothesis that specific microRNAs participate directly to the onset of these diseases, and for this reason they represent a target that we can use to develop novel therapies against them.

PI_NAMEs: PRATICO, DOMENICO  (contact)

PROJECT_TERMS: abnormally phosphorylated tau;Address;Affect;Age;age related;Aging;Alzheimer's Disease;Astrocytes;Autophagocytosis;Autopsy;Behavioral;behavioral impairment;Biological;Brain;Brain Diseases;brain health;brain parenchyma;brain tissue;Cell Physiology;Cells;Central Nervous System;Clinical;clinical phenotype;cognitive function;Communities;corticobasal degeneration;Data;Dementia;Dependovirus;Development;Disease;disease phenotype;Disease Progression;effective therapy;Elderly;Etiology;Event;Evolution;Excision;Functional disorder;Gene Delivery;Goals;Hippocampus;hTau Mice;Human;Impairment;Individual;interest;Literature;Mediating;Memory impairment;Memory Loss;Metabolic Pathway;Metabolism;Microglia;MicroRNAs;Modeling;mouse model;Mus;Nerve Degeneration;Neurobiology;Neurodegenerative Disorders;neuroinflammation;Neurons;neuropathology;novel;novel therapeutic intervention;novel therapeutics;Onset of illness;Organ;organ growth;overexpression;Paper;Pathogenesis;Pathogenicity;Pathologic;Pathology;Phenotype;Phosphoric Monoester Hydrolases;Phosphotransferases;Pick Disease of the Brain;Play;posttranscriptional;prevent;Preventive measure;Process;programs;Progressive Supranuclear Palsy;Regulation;Research;Research Proposals;RNA Splicing;Role;Secondary to;small molecule;Source;Synapses;synaptic function;tau aggregation;tau Proteins;tau-1;Tauopathies;Testing;Therapeutic;therapeutically effective;Time;tool;Transgenic Mice;Untranslated RNA

PROJECT_TITLE: Alzheimer's tauopathy phenotype and the microRNA22-3p: implication for pathogenesis


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cerebrovascular;Neurosciences;Stroke

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROSURGERY

ORG_NAME: WASHINGTON UNIVERSITY

PHR: Project Narrative The largest treatable causes of poor outcome after brain aneurysm rupture (termed subarachnoid hemorrhage or SAH) are Early Brain Injury (EBI) and Delayed Cerebral Ischemia (DCI). In the present proposal, we plan to capitalize on the body's innate protective machinery to resist injury (a phenomenon called “conditioning”) to combat EBI and DCI. In particular, we will test two novel conditioning-based therapies (NAMPT activation and NAD+ augmentation), which if successful will establish drugs targeting NAMPT and NAD+ as new and promising treatment strategies for patients with ruptured brain aneurysms.

PI_NAMEs: ZIPFEL, GREGORY J (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: 3-Dimensional;Address;aged;Anabolism;Aneurysmal Subarachnoid Hemorrhages;Arteries;Automobile Driving;Blood - brain barrier anatomy;blood-brain barrier disruption;Brain;Brain Aneurysms;Brain Injuries;Cerebral Ischemia;cofactor;Cognitive deficits;combat;conditioning;Deacetylase;design;Drug Targeting;Edema;Elements;Endothelial Cells;Enzymes;Experimental Models;Exposure to;Female;Functional disorder;Genetic;Grant;Hypoxia;improved;Individual;inhibitor;Injections;Injury;knock-down;Knockout Mice;Life;male;Mediating;Mediator;Methods;Modeling;Molecular;mouse model;Mus;neurobehavioral;Neurocognitive Deficit;neurocognitive test;neuroinflammation;Neurologic Deficit;neuron loss;Neurons;neurovascular;new therapeutic target;Niacinamide;Nicotinamide Mononucleotide;nicotinamide phosphoribosyltransferase;novel;novel therapeutics;Outcome;overexpression;Pathway interactions;Patients;Perforation;pharmacologic;Play;pleiotropism;preconditioning;prevent;Process;Production;protective effect;Resistance;Role;Rupture;Ruptured Aneurysm;Secondary to;SIRT1 gene;Stimulus;Stress;Subarachnoid Hemorrhage;Survivors;Testing;Therapeutic;Thrombus;Transgenic Mice;translational potential;treatment strategy;Vasospasm;Wild Type Mouse;Work

PROJECT_TITLE: Roles of NAMPT and NAD+ in hypoxic conditioning-induced neurovascular protection in subarachnoid hemorrhage

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


NIH_SPENDING_CATS: Aging;Assistive Technology;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Neurosciences;Patient Safety;Rehabilitation

ORG_CITY: BALTIMORE

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative Severe bilateral loss of vestibular sensation – the inner ears’ sense of balance – causes chronic dizziness, blurry vision during head movement, a constant need to exert conscious effort to do things that are normally automatic (like walking without wobbling or falling), and inability to drive or swim safely. For older individuals who are already contending with decreases in vision and other senses that normally contribute to maintaining balance, loss of vestibular sensation may be even more impactful. In first-in-human trial already underway with patients ranging in age from 51-66 years, we found that a vestibular implant system that senses head motion and electrically stimulates the vestibular nerve (similar to how cochlear implants help people with severe hearing loss) can improve the signs and symptoms of bilateral vestibular loss. The project we now propose will extend this line of research to focus on older individuals, with the goal of determining whether the risks and degree of benefit they experience is similar to those already observed in younger adults.

PI_NAMEs: DELLA SANTINA, CHARLES C (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: 3-Dimensional;Adult;Adverse event;Affect;Age;age related;aged;Anatomy;arm;Auditory;Benefits and Risks;Bilateral;burden of illness;Chronic;Clinical;Clinical Research;Cochlear implant procedure;Cochlear Implants;Cognition;cognitive load;cognitive task;cohort;comorbidity;Compensation;Conscious;cost;Data;Databases;Decision Making;design;Devices;disability;disabled;Disabled Persons;Disabling;Dizziness;Ear;Effectiveness;effectiveness evaluation;efficacy evaluation;Electric Stimulation;Equilibrium;Esthesia;Exclusion;experience;Face;fall risk;falls;Feasibility Studies;first-in-human;follow-up;Funding;Gait;Goals;Grant;Head;Head Movements;health related quality of life;Hearing;hearing impairment;high risk;Home;human old age (65+);Hypesthesia;Impaired cognition;Implant;implantation;improved;Incidence;Individual;Intervention;Journals;Knowledge;Laboratories;Labyrinth;Life;Measurement;Measures;Medical;Medicine;middle age;Motion;Natural History;Nerve;New England;Observational Study;older adult;Older Population;open label;Operative Surgical Procedures;Organ;otoconia;Outcome;Participant;Patient Outcomes Assessments;Patients;Performance;Perioperative;Persons;Placebos;Policy Maker;Posture;posture instability;Proprioception;Prosthesis;Protocols documentation;Rehabilitation therapy;Relative Risks;Reporting;Research;Research Design;response;restoration;Risk;Rotation;Running;Safety;safety testing;Self-Help Devices;Semicircular canal structure;senescence;Sensory;Signs and Symptoms;standard of care;Stimulus;Swimming;System;Testing;Therapeutic;Third-Party Payer;Time;United States Food and Drug Administration;Vestibular function;Vestibular Labyrinth;Vestibular loss;Vestibular Nerve;vestibular prosthesis;vestibular system;vestibulo-ocular reflex;Vision;Walking;way finding;Work;young adult

PROJECT_TITLE: Vestibular implantation in older adults

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]