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

ORG_CITY: Los Angeles

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Project Narrative Gains in life expectancy and population aging are driving a sharp rise in Alzheimer's Disease and Related Dementias (ADRD), emphasizing the importance of identifying factors that can protect against ADRD risk and cognitive decline in older ages. We will study how education quantity and quality affect cognition and ADRD risk, and investigate the role of genetics in driving ADRD risk as well as in moderating the relationship between education and ADRD risk.

PI_NAMEs: BARCELLOS, SILVIA HELENA (contact)

PROGRAM_OFFICER_NAME: BRAUDT, DAVID BRUCE

PROJECT_TERMS: Affect;Age;Aging;aging population;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Automobile Driving;Behavioral;biobank;Body mass index;Cessation of life;Characteristics;Childhood;Clinical;Cognition;Cognitive;cognitive function;cognitive testing;cohort;Conceptions;conditioning;Data;Data Set;Dementia;dementia risk;design;Diagnosis;disparity reduction;Education;Educational Curriculum;Family;family genetics;Finland;Genes;Genetic;genetic analysis;Genetic Databases;Genetic Risk;Genotype;Geography;Health;health disparity;health record;higher education;Hospitalization;human old age (65+);Impaired cognition;improved;indexing;Individual;Intelligence;International;Intervention;Knowledge;late life;Life;Life Expectancy;Link;Liquid substance;Measures;Natural experiment;Netherlands;Outcome;Parents;Participant;Persons;Policies;Policy Maker;Prevalence;primary care visit;Process;processing speed;prospective memory;Pupil;Registries;Research;residence;Respondent;Risk Factors;Role;Running;Sampling;Schools;Smoking;Source;Student Selections;Students;Surveys;teacher;Variant;visual memory;Vocation

PROJECT_TITLE: Genetic Differences in the Causal Effect of Education Quantity and Quality on Cognitive Functioning and Dementia Diagnosis Later in Life


ADMINISTERING_IC: AG

ARRA_FUNDED: N

FUNDING_MECHANISM: SBIR-STTR RPGS

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);Assistive Technology;Behavioral and Social Science;Bioengineering;Brain Disorders;Burden of Illness;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Disability Research;Health Services;Mental Health;Neurodegenerative;Neurosciences;Palliative Care;Rehabilitation;Social Determinants of Health

ORG_CITY: Atlanta

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: MAPHABIT, INC.

ORG_STATE: GA

PHR: Caregiving is commonly acknowledged as one of the most stressful, under-recognized, under- paid, and under-supported jobs. The new MapHabit System Caregiver Training Program (CTP) will offer a technology-driven caregiver training platform that will train caregivers to be more knowledgeable about memory and dementia while also learning to better manage their own stress and their quality of life needs. In this way, caregivers can be more innovative in their care strategies using person-centered wellness plans and thoughtful decision processes. Informed patient care reinforces effective caregiving, reduces patient emergency visits, hospitalizations, caregiver dropout, and reduces overall burden on the healthcare system.

PI_NAMEs: GOLDEN, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: HARRELL, ERIN

PROJECT_TERMS: acceptability and feasibility;Activities of Daily Living;Address;Alzheimer's disease related dementia;Brain;Brain region;burnout;Businesses;Calendar;care coordination;Caregiver Burden;caregiver education;caregiver quality of life;Caregiver support;Caregiver well-being;Caregivers;caregiving;Caring;Categories;Client satisfaction;Cognition;cognitive testing;commercialization;Communication;Communities;community building;cost;Critical Thinking;dashboard;Data;Dementia;dementia care;design;Dropout;Education;Effectiveness;Emergency Situation;Emotional;experience;Family;family burden;Family Caregiver;family caregiving;functional status;Guidelines;Habits;Health;Health care facility;Healthcare Systems;Home;Hospitalization;Hospitals;Impaired cognition;improved;Individual;Information Networks;innovation;Knowledge;Learning;Legal patent;Libraries;Life Experience;Managed Care;Maps;Marketing;Measurable;Measures;Memory;memory care;Mental Health;mHealth;Mobile Health Application;Motivation;Neurosciences;Occupations;Outcome;Participant;Patient Care;Patient Self-Report;Patient-Focused Outcomes;Patients;Performance;person centered;Personal Satisfaction;Persons;Phase;physical conditioning;Process;programs;Progressive Disease;Provider;Publishing;Quality of Care;Quality of life;response;Risk;Role;Schedule;Self Care;Self Perception;Self-Help Devices;skills;Small Business Innovation Research Grant;smart device;social;Social Network;Social support;Standardization;Stress;Support System;System;Systems Integration;Technology;technology platform;Training;Training Programs;usability;Visit;visual map;Voice;Wellness Center;Work

PROJECT_TITLE: An assistive-technology based Caregiver Training Program (CTP) to enhance caregiver effectiveness, well-being, and quality of life, which will improve overall care for individuals living with AD/ADRD.


ADMINISTERING_IC: DK

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: The working hypothesis of this program is that RNA editing in mouse and human islets is an important determinant of islet cell function, and is essential for preventing islet inflammation due to endogenous double- stranded RNA. We propose experiments in mice and in human islets to determine the consequences of disrupted RNA editing in alpha and beta cells, including a potential contribution to autoimmunity. 1

PI_NAMEs: DOR, YUVAL ;LEVANON, EREZ ;POWERS, ALVIN C (contact)

PROGRAM_OFFICER_NAME: BASU, RAJATAVA

PROJECT_TERMS: Abbreviations;adaptive immunity;Adenosine;adenosine deaminase;Adult;Alpha Cell;anterior chamber;Anti-viral Response;Antibodies;Architecture;Autoantibodies;Autoimmunity;B-Lymphocytes;Beta Cell;Biology;Cell Physiology;Cell Separation;cell type;Cells;Cellular biology;Characteristics;Code;Collaborations;Computer Analysis;cytosolic receptor;D Cells;Dangerousness;Deamination;Dependence;Detection;Development;Diabetes autoantibodies;diabetes pathogenesis;Double-Stranded RNA;dsRNA adenosine deaminase;Elements;endocrine pancreas development;Enzymes;epitranscriptomics;experimental study;eye chamber;Functional disorder;Gene Expression;Genes;Genetic;Genetic Transcription;Genome;genome wide association study;Genomics;Goals;Health;Human;Human Genome;humoral immunity deficiency;IFIH1;Immune;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;Impairment;in vivo;indexing;Inflammation;Inflammatory;Inflammatory Response;Inosine;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;Interferons;islet;Islet Cell;knock-down;Knock-out;Malignant Neoplasms;Mature B-Lymphocyte;Mediating;Modification;Molecular;Molecular Biology;mouse model;multiplexed imaging;Mus;Organ;Pancreas;Pathogenicity;Phenotype;postnatal;pre-clinical;prevent;Prevention;programs;protective allele;Proteins;Rag1 Mouse;Research;Research Design;response;Retroelements;Risk;RNA;RNA Editing;Role;sensor;single-cell RNA sequencing;Structure;T-Cell Depletion;T-Lymphocyte;Testing;Tissue-Specific Gene Expression;transcriptome;Viral;Work

PROJECT_TITLE: RNA editing in islet function and inflammation

STUDY_SECTION: CSME

STUDY_SECTION_NAME: Cell Signaling and Molecular Endocrinology Study Section[CSME]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Aging;Biotechnology;Contraception/Reproduction;Genetics;Human Genome;Women's Health Research

ORG_CITY: BERKELEY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

ORG_STATE: CA

PHR: Project narrative Female reproductive aging in mammals is associated with altered retrotransposon expression, and altered retrotransposon-mediated gene regulation. Using genomics, mouse genetics, cell and molecular biology approaches, we propose to comprehensively catalog the expression of retrotransposons and retrotransposon:gene isoforms during female reproductive aging, and to investigate their functions in regulating the aging of oocyte and somatic granulosa cells.

PI_NAMEs: HE, LIN  (contact);WANG, TING

PROGRAM_OFFICER_NAME: GUO, MAX

PROJECT_TERMS: aged;Aging;Biology;blastocyst;Catalogs;Cell Aging;Cellular biology;Clustered Regularly Interspaced Short Palindromic Repeats;Code;CRISPR interference;Data;Development;differential expression;Dimensions;Disease;DNA Damage;Elements;Epigenetic Process;Event;Exhibits;Exons;Family;Female;Gene Expression;Gene Expression Regulation;Gene Silencing;Gene Structure;Genes;Genome;Genome engineering;Genomics;granulosa cell;Impairment;In Vitro;Innate Immune Response;insight;interdisciplinary approach;mammalian genome;Mammals;Maps;Mediating;Meiosis;Molecular;Molecular Biology;mouse genetics;Mouse Strains;Mus;N-terminal;nanopore;old mice;Oocytes;overexpression;Physiology;Play;Polyadenylation;posttranscriptional;Pre-implantation Embryo Development;pro-aging;Production;promoter;Protein Isoforms;Proteins;Repression;reproductive senescence;response;Retrotransposition;Retrotransposon;RNA;RNA Interference;Role;Signal Transduction;single-cell RNA sequencing;Small Interfering RNA;Somatic Cell;System;Technology;Tissues;Transcript;transcriptome sequencing

PROJECT_TITLE: The role of retrotransposons in female reproductive aging


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Genetics;Macular Degeneration;Neurodegenerative;Neurosciences

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: 8. PROJECT NARRATIVE This project aims to identify a pathogenic pathway mediating fibrosis in age-related macular degeneration (AMD). Since fibrosis is a major cause of blindness in AMD patients, the proposed studies will enhance our understanding of this blinding disorder. The information generated from this project will also reveal a new drug target for the treatment of subretinal fibrosis to prevent vision loss in AMD patients.

PI_NAMEs: TAKAHASHI, YUSUKE  (contact)

PROGRAM_OFFICER_NAME: SHEN, GRACE L

PROJECT_TERMS: Adenoviruses;Age related macular degeneration;Animal Model;Attenuated;beta catenin;Biological Assay;Blindness;Blocking Antibodies;Blood Vessels;Cell Line;cell type;Cells;Choroidal Neovascularization;conditional knockout;connective tissue growth factor;CRISPR/Cas technology;Crossbreeding;Disease;E-Cadherin;Enzyme-Linked Immunosorbent Assay;Epithelium;Extracellular Domain;Extravasation;Fibronectins;Fibrosis;Genes;Genetic Transcription;Human;Hypoxia;Inflammation;Intercellular adhesion molecule 1;Interruption;Knock-out;knockout gene;Knockout Mice;Lasers;Length;Leukostasis;Ligands;Luciferases;Mediating;Mesenchymal;Modeling;Molecular;Mus;N-terminal;neovascularization;new therapeutic target;Nonexudative age-related macular degeneration;overexpression;Pathogenicity;Pathology;Pathway interactions;Patients;Phenotype;Photoreceptors;Play;prevent;receptor;Regulation;Reporting;Retina;retinal rods;Rod;Role;slug;Snails;stressor;System;targeted treatment;TNF gene;Transforming Growth Factor Beta 2;Transgenic Mice;Vascular Endothelial Growth Factors;Vimentin;VLDL receptor;Wild Type Mouse;WNT Signaling Pathway

PROJECT_TITLE: Dysregulation of Wnt signaling in subretinal fibrosis in AMD

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


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

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Project Narrative (3 sentences). Advanced chronological age is the greatest risk factor for developing Alzheimer’s disease, the most common cause of dementia and the only top ten cause of death in America without an effective treatment. This research proposal will closely investigate an aging process that recently has been recognized for its role in Alzheimer’s disease, called cellular senescence. The results will reveal how cellular senescence changes in the brain throughout the adult human lifespan in health and during progressive stages of Alzheimer’s disease, which may unveil new targets for developing disease-modifying therapies.

PI_NAMEs: ORR, MIRANDA ETHEL (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: Adult;Age;age related changes;aging process;Alzheimer's Disease;Apoptosis;Automobile Driving;Autopsy;biobank;biological adaptation to stress;Biological Aging;Biology of Aging;Brain;Brain Diseases;brain health;brain tissue;Cause of Death;Cell Aging;Cell Cycle;Cell Cycle Arrest;Cell Death;Cell Differentiation process;cell injury;Cells;Cellular biology;Chronic;Chronology;Clinical;Color;Data;Dementia;Deposition;digital;Disease;Disease Progression;effective therapy;Elderly;entorhinal cortex;Environment;experimental study;Functional disorder;Gene Expression;Germ Cells;Health;Histologic;Human;Inflammation;Inflammatory;Intervention;laser capture microdissection;Lasers;Life;life span;Link;Mediating;Mediator;Methods;Molecular;Nerve Degeneration;Neurofibrillary Tangles;neuronal patterning;Neurons;Neurosciences;Neurosciences Research;new therapeutic target;novel;novel therapeutics;Oranges;Participant;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Pattern;pharmacologic;Phenotype;Population;postmitotic;Process;protein expression;Research;Research Proposals;Resolution;Risk Factors;Role;senescence;senescence associated secretory phenotype;senescent cell;single nucleus RNA-sequencing;Source;Stereotyping;tau aggregation;tau Proteins;Tauopathies;Testing;tissue degeneration;Tissues;Toxic effect;transcriptomics;Transgenic Mice;Translating;treatment strategy;Universities;Washington

PROJECT_TITLE: High Resolution Profiling of Senescent Neurons and Their Microenvironments in Postmortem Human Brain Tissue Spanning Eight Decades of Life

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-A(50)R]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences;Pediatric

ORG_CITY: DURHAM

ORG_DEPT: NEUROSCIENCES

ORG_NAME: DUKE UNIVERSITY

PHR: PROJECT NARRATIVE It remains considerably challenging to restore vision after retinal degeneration and developmental disturbances, including infantile nystagmus, as the mechanisms underlying functional connectivity between retinal ganglion cells and their downstream targets remain poorly understood. This project investigates how direction-selective retinal ganglion cells drive motion-sensitive neurons across the zebrafish brain over development to elicit the visually guided optomotor response. health and disease Insights into how entire visuomotor neural circuits assemble and function in are likely to be of critical importance for the development of regenerative treatment strategies.

PI_NAMEs: NAUMANN, EVA AIMABLE (contact)

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Affect;Algorithms;Area;Behavior;behavior test;Behavioral;behavioral response;Biological Models;Blindness;Brain;Calcium;Cells;Classification;Collaborations;Congenital Disorders;critical developmental period;Data;design;Development;developmental disease;Disease;Equilibrium;experimental study;Eye;fascinate;Fertilization;Genes;Goals;Health;high dimensionality;Holography;Image;Individual;infancy;Injury;insight;Knowledge;Life;Link;loss of function;Maintenance;Mammals;Maps;Measures;Modeling;monocular;Motion;Motor output;mutant;Natural regeneration;Nature;network models;neural;neural circuit;neural correlate;neurodevelopment;neurogenesis;Neurons;Newborn Infant;novel;Optics;optogenetics;Pathologic Nystagmus;Phase;Population Dynamics;predicting response;predictive modeling;preference;Process;Recurrence;recurrent neural network;regenerative treatment;Research Design;Resolution;response;Retina;Retinal Degeneration;Retinal Ganglion Cells;Role;sensory input;Shapes;sight restoration;Signal Transduction;stem;Stimulus;Study models;Swimming;Target Populations;Testing;Time;Training;treatment strategy;two photon microscopy;Vision;vision development;Visual;Visual Motion;visual motor;visual processing;Visual System;Zebrafish

PROJECT_TITLE: Development of brain-scale neural circuits underlying vertebrate visuomotor transformations

STUDY_SECTION: NBVP

STUDY_SECTION_NAME: Neuroscience of Basic Visual Processes Study Section[NBVP]


ORG_CITY: South San Francisco

ORG_NAME: ENABLE BIOSCIENCES, INC.

PHR: Testing for the presence of risk factors for type 1 diabetes in blood before symptoms arise helps reduce the occurrence of deadly complications, while also establishing eligibility for potential treatments that can delay or prevent the onset of diabetes. Enable Biosciences proposes to achieve FDA clearance and establish quality systems for an accurate test for diabetes risk that can use easy-to-collect dry blood spot samples. Such a test will allow more people to get conveniently tested for diabetes risk and determine their eligibility for potentially lifesaving treatments.

PI_NAMEs: SEFTEL, DAVID  (contact)

PROGRAM_OFFICER_NAME: ARREAZA-RUBIN, GUILLERMO

PROJECT_TERMS: Affect;Agglutination;American;antibody detection;Autoantibodies;Autoimmune Diseases;Award;Bilirubin;Biological Assay;Biological Markers;Biological Sciences;Blinded;Blood;Blood capillaries;Chronic;Clinical;Clinical Research;Collaborations;Collection;Data;Dependence;design;detection assay;detection limit;Devices;Diabetes autoantibodies;Diabetes Mellitus;diabetes risk;Diabetic Ketoacidosis;Diagnosis;Dryness;Eligibility Determination;Enrollment;hazard;Hemoglobin;Home;Hybridomas;IA-2 antibody;Individual;innovation;Insulin;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;Intervention;Islet Cell;islet cell antibody;Laboratories;Legal patent;Life;Lipids;manufacture;manufacturing quality;manufacturing test;Methods;National Institute of Diabetes and Digestive and Kidney Diseases;Organ;Pancreas;Pathway interactions;Performance;Persons;Phase;Plasma;prevent;Process;Production;Protocols documentation;Publishing Peer Reviews;Reagent;Regulation;Reporting;Reproducibility;Risk;Risk Factors;sample collection;Sampling;screening program;Serum;Signal Transduction;Site;Small Business Innovation Research Grant;Specific qualifier value;Speed;Spottings;success;Symptoms;System;Technology;Testing;usability;Validation;validation studies;Whole Blood

PROJECT_TITLE: Advancing an accessible, high-throughput and multiplex islet autoantibody test with self-collected capillary dried blood spots for regulatory clearance

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-EMS-K(10)B]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Health Services;Neurodegenerative;Palliative Care

ORG_CITY: NEW YORK

ORG_NAME: VISITING NURSE SERVICE OF NEW YORK

ORG_STATE: NY

PHR: PROJECT NARRATIVE Family caregivers often act as an extension of the care team during home health care for older adults, yet their capacity and needs are not systematically assessed which limits their access to necessary support. This proposal would develop, refine, and pilot test a self-assessment intervention for the home health setting to improve communication and support between the care team and family caregivers to patients with Alzheimer’s Disease and Related Dementias. Proposed research and training activities would support the career development of Dr. Julia Burgdorf, whose career goal is to improve home- and community-based care for older adults by developing pragmatic clinical interventions to advance provider-led engagement and support of family caregivers.

PI_NAMEs: BURGDORF, JULIA  (contact)

PROGRAM_OFFICER_NAME: FAZIO, ELENA

PROJECT_TERMS: Address;Admission activity;Adverse event;Advisory Committees;aging in place;Alzheimer's disease patient;Alzheimer's disease related dementia;Ambulatory Care;Area;Assessment tool;beneficiary;care outcomes;care recipients;career;career development;Caregiver support;Caregivers;caregiving;Caring;Clinical;clinical care;Collaborations;Communication;Communities;community based care;community living;cost;Data;Data Collection;Dementia caregivers;demographics;design;Deterioration;Discipline of Nursing;Doctor of Philosophy;effective intervention;Electronic Health Record;Electronics;Eligibility Determination;empowerment;Evaluation;experience;Face;Family;Family Caregiver;family support;Feedback;Focus Groups;Fostering;Funding;Future;Goals;Grant;Health;health care availability;health care quality;health care referral;health care settings;Health Personnel;Health system;Healthcare;Healthcare Industry;Home;Home Care Services;Hospitalization;Hour;human centered design;improved;Individual;informant;Infrastructure;innovation;Institutionalization;Intake;Intervention;intervention refinement;Intervention Studies;Interview;Lead;Learning;Letters;Link;Measures;Medical;Medicare;meetings;Mentors;Mentorship;Methods;Modality;multidisciplinary;Needs Assessment;nonalzheimer dementia;Notification;Nursing Services;nursing skill;older adult;Online Systems;Outcome;Pathway interactions;Patient Care;patient home care;Patient risk;Patients;Persons;Pilot Projects;pilot test;Policies;portability;Positioning Attribute;Pragmatic clinical trial;Process;prototype;Provider;Randomized;Reporting;Research;Research Activity;Research Personnel;Resources;Risk;Running;Sampling;satisfaction;Schedule;Scientist;Self Assessment;Self Efficacy;Services;skills;Source;stakeholder perspectives;Surveys;Technology;technology platform;Testing;therapy design;Time;Training;Training Activity;treatment as usual;Visiting Nurse;Work;Workload;Writing

PROJECT_TITLE: Supporting Dementia Caregivers During Medicare Home Health: Developing the DECLARE Needs Assessment Intervention

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics;Hematology;Infectious Diseases;Lymphatic Research;Lymphoma;Pediatric;Primary Immunodeficiencies;Rare Diseases

ORG_DEPT: PATHOLOGY

PHR: Project Narrative  V(D)J recombination and class switch recombination are two independent site-specific gene rearrangement processes that are essential for a healthy immune system, and when either of these gene rearrangement processes sporadically fail in humans, malignant tumors can develop. These account for the most common malignancies in young children, and account for most of those arising from the blood cells (leukemia and lymphoma); moreover, inherited defects in these processes also occur, accounting for the most common congenital immunodeficiencies. This proposal seeks to understand the mechanistic basis for these sporadic and inherited failures, knowledge of which is essential to predict clinical consequences and to genetically correct many of the defects.

PI_NAMEs: LIEBER, MICHAEL R (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Accounting;activation-induced cytidine deaminase;Antibodies;B lymphoid malignancy;B-Lymphocytes;Behavior;Biochemical;Biochemistry;Biological Assay;Blood Cells;Child;Chromosomal Breaks;Chromosome Pairing;Chromosomes;clinical predictors;Complex;congenital immunodeficiency;Cryoelectron Microscopy;Defect;Disease;DNA;Enzymes;Ephrin-A5;Failure;Funding;Gene Rearrangement;Genetic Recombination;Health;Human;Immune system;immunodeficiency;Immunoglobulin Class Switching;Immunoglobulin Switch Recombination;Immunoglobulins;improved;Inherited;Knowledge;Length;leukemia/lymphoma;Malignant Neoplasms;Nature;Neoplasms;neoplastic;Nonhomologous DNA End Joining;pathogenic bacteria;pathogenic virus;Pathway interactions;Phase;Polynucleosome;Positioning Attribute;premature;Process;protein purification;Proteins;Publishing;reconstitution;Resolution;single molecule;single-molecule FRET;Site;structural biology;Structure;System;Technology;V(D)J Recombination

PROJECT_TITLE: Site-Specific Recombination in Human Health & Disease

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


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

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

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: NARRATIVE: Reducing human immunodeficiency virus (HIV) infections in the US, which are increasingly concentrated in Southern states with a large rural HIV burden, will require interventions tailored to local-level epidemic dynamics that address racial and ethnic disparities and underlying drivers of transmission. We will partner with three state health departments where we have established relationships (Alabama, Louisiana, and Mississippi) to develop a suite of HIV transmission models that link rural and urban region and incorporate insurance, access to health care, housing instability, and the opioid epidemic. These models will project the likely impact of interventions that address HIV as well as social determinants of health and opioid misuse, to fill an urgent, unmet need for evidence-based guidance in prioritizing local interventions in the service of ending the HIV epidemic in states with a large rural burden of HIV.

PI_NAMEs: FOJO, ANTHONY TODD (contact)

PROGRAM_OFFICER_NAME: HUELSNITZ, CHLOE OLIVIA

PROJECT_TERMS: Address;Affect;AIDS prevention;Alabama;Behavior;Calibration;Caring;Censuses;Centers for Disease Control and Prevention (U.S.);Cities;Continuity of Patient Care;Data;design;Disease remission;Disparity;Drug usage;Economic Models;Education;Enrollment;Epidemic;epidemiological model;ethnic disparity;ethnic minority;Ethnic Origin;evidence base;Geographic Locations;Geography;Goals;Harm Reduction;Health;health care availability;health care service;Health Resources;Health Services Accessibility;Healthcare Systems;HIV;HIV Infections;Home;Housing;housing instability;Human immunodeficiency virus test;illicit opioid;improved;Incidence;Infection;Insurance;Insurance Coverage;Intervention;Link;literature survey;Louisiana;mathematical model;medication for opioid use disorder;Mississippi;Modeling;Opioid;opioid epidemic;opioid misuse;opioid use;opioid use disorder;Policies;Population;Poverty;pre-exposure prophylaxis;prescription opioid;Prevalence;Prevention;Preventive;programs;Public Health;Race;racial disparity;racial minority;Reporting;Resources;Rural;rural America;rural area;Rural Community;screening;Services;sexual minority;social determinants;social health determinants;Subgroup;surveillance data;Surveys;Taxes;Testing;tool;transmission process;U.S. Department of Housing and Urban Development;United States;uptake;urban area;Viral;Virus Diseases;Vulnerable Populations;web-based tool

PROJECT_TITLE: Ending the HIV Epidemic in Rural America (EHE-RA): Local Interventions, Co-Epidemics, and Social Determinants

STUDY_SECTION: PPAH

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


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Epilepsy;Genetics;Infectious Diseases;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health;Vector-Borne Diseases

ORG_CITY: LOS ANGELES

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative Despite the high burden of epilepsies in sub-Saharan Africa, many commonly occurring epilepsies remain understudied and poorly characterized. This proposal focuses on improving our understanding of the role of host genetics and its relationship to exposure to Onchocerca volvulus, a commonly occurring parasite, in the manifestation of epilepsy. Advances from these studies will provide mechanistic insights into epileptogenesis of acquired epilepsies and new targets for developing preventive measures.

PI_NAMEs: MAZUMDER, RAJARSHI  (contact)

PROGRAM_OFFICER_NAME: HAYES, UNJA

PROJECT_TERMS: acquired epilepsy;Affect;Africa South of the Sahara;African;aged;Antibodies;Antigens;Antiparasitic Agents;arthropod-borne;Autoimmunity;Blood;Board Certification;Brain Diseases;California;career;career development;Child;Clinical;clinical examination;Communities;Convulsions;Country;Data;design;Development Plans;Disease;DNA;Drops;early detection biomarkers;Early identification;Economic Burden;Electroencephalography;Electrophysiology (science);Environmental Risk Factor;epidemiology study;Epilepsy;Epileptogenesis;Etiology;Evaluation;exome sequencing;Exposure to;Family;Family member;Foundations;Funding;Future;Genes;Genetic;Genetic Polymorphism;genetic variant;Genetic Variation;global health;Goals;Grant;Head;High Prevalence;Household;Human;Immune response;Impaired cognition;improved;Incidence;Income;Individual;insight;Interview;Intestinal Volvulus;Lead;Los Angeles;member;Mentors;Modeling;Molecular Epidemiology;Molecular Mimicry;Muscle;neglected tropical diseases;Onchocerca volvulus;Onchocerciasis;Parasites;Parasitic Diseases;Parents;Participant;Pathogenesis;Persons;Phenotype;population health;Predisposition;Prevalence;prevent;Preventive measure;Primary Prevention;proband;Proteins;recruit;Research;Research Design;Research Personnel;Resource-limited setting;Resources;responsible research conduct;Risk;risk mitigation;Role;Second Degree Relative;segregation;Seizures;Serum;Siblings;socioeconomics;Standardization;Syndrome;Testing;Time;Training;trait;Tribes;Uganda;United States;Universities;Variant;Work;Writing

PROJECT_TITLE: Etiological Role of Parasitic Exposure and Familial Susceptibility in Nodding Syndrome-Related Epilepsies

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-ICP-G(55)R]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: SAINT LOUIS

ORG_DEPT: PSYCHIATRY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE There is a major unmet need for the treatment of depression because current pharmacotherapies for depression require prolonged administration for clinical improvement and they are often associated with high non-response rate. Recent clinical evidence has shown that a single sub-anesthetic dose of ketamine, a glutamate-NMDA receptor antagonist, induces a robust antidepressant effect within hours of treatment in 70% of treatment- resistant patients, however a circuit and synaptic-level dissection of ketamine’s mechanisms of action is lacking. Accordingly, the goal of this proposal is to identify circuits, cellular and molecular determinants responsible for the rapid antidepressant action of ketamine.

PI_NAMEs: PIGNATELLI, MARCO  (contact)

PROGRAM_OFFICER_NAME: HUPALO, SOFIYA

PROJECT_TERMS: Acute;Address;Affect;AMPA Receptors;Anesthetics;Anhedonia;antagonist;anti-depressive agents;antidepressant effect;Atrophic;Behavior;Behavioral;behavioral outcome;Brain;burden of illness;cell type;Cells;Chronic stress;Clinical;Consensus;Data;Dendritic Spines;depressive symptoms;design;disability;Dissection;Dose;DRD2 gene;Electrophysiology (science);Elements;experimental study;Exposure to;Functional disorder;Genetic;genetic approach;Glutamates;Goals;Guanosine Triphosphate Phosphohydrolases;Homosynaptic Depression;Hour;improved;in vivo;innovation;insight;interest;Ketamine;Knock-in Mouse;Laboratory Animals;Link;Literature;Major Depressive Disorder;Medial;Mediating;Mental Depression;Molecular;Molecular Target;Morbidity - disease rate;mortality;Motivation;Mus;Neurons;neurotransmission;new therapeutic target;NMDA receptor antagonist;novel;Nucleus Accumbens;optogenetics;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Physiology;pleasure;Population;pre-clinical;Prefrontal Cortex;prevent;promoter;Protein Biosynthesis;Protein Synthesis Inhibition;Proteins;public health priorities;rational design;Resistance;reward circuitry;Rewards;Slice;spatiotemporal;Specific qualifier value;Stress;Symptoms;Synapses;Synaptic plasticity;Synaptic Transmission;synaptogenesis;Technology;Testing;therapeutic target;Transgenic Mice;transmission process;Treatment Efficacy

PROJECT_TITLE: A synaptic substrate for ketamine-mediated amelioration of stress-induced anhedonia

STUDY_SECTION: PMDA

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


NIH_SPENDING_CATS: Genetics

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: BIOLOGY

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: PROJECT NARRATIVE Genetic variation can cause individuals to differ in how they respond to their environment, leaving some human individuals susceptible to particular complex diseases. By understanding the evolutionary forces causing genetic-environmental interactions we may better understand the genetic origins of complex disease. As technology advances, expanded personal environmental data will allow greater investigation of genetic-environmental interactions in human health, and the genetic signatures of environmental adaptation can be leveraged to make predictions and decisions for human health.

PI_NAMEs: LASKY, JESSE  (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TITLE: Evolutionary genetics of genotype-by-environment interactions for complex traits

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


ADMINISTERING_IC: HL

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Narrative Understanding the basic biology of viral vectors and how best to transduce stem cells and keep these cells in efficient gene-expressing and engrafting form is crucial to the future successes of gene therapy. This training will provide the next generation of scientists in this exciting, but still not fully-realized translational and clinical, discipline of gene regulation and therapy for the health benefit of our citizens.

PI_NAMEs: HERZOG, ROLAND W. (contact);KAPUR, REUBEN

PROGRAM_OFFICER_NAME: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN

PROJECT_TERMS: Basic Science;gene therapy;Hematological Disease

PROJECT_TITLE: Basic Sciences Studies on Gene Therapy of Blood Diseases

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM(JA)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Lung;Prevention;Rare Diseases;Tuberculosis

ORG_CITY: ALBANY

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: ALBANY MEDICAL COLLEGE

PHR: PROJECT NARRATIVE Pulmonary tuberculosis caused by Mycobacterium tuberculosis (TB) is one of the top causes of mortality and morbidity from infectious diseases. With the ongoing COVID19 pandemic, TB care has been severely compromised across the globe, resulting in a sharp increase in mortality and morbidity. The proposed research is relevant to public health as it seeks to understand how alveolar epithelial cells in the lung communicate with innate immune cells to mediate early protection from TB and identify mechanisms that compromises these protective immune responses resulting in disease progression. The knowledge to be gained will have direct implications in designing therapeutics or vaccines to target such mechanisms to boost TB immunity.

PI_NAMEs: MISHRA, BIBHUTI BHUSAN (contact)

PROGRAM_OFFICER_NAME: MONGODIN, EMMANUEL FRANCK

PROJECT_TERMS: Aerosols;Affect;airway epithelium;Alveolar;alveolar epithelium;Animals;Anti-Bacterial Agents;Antibiotic Therapy;Antibodies;antimicrobial;Antimycobacterial Agents;Bacteria;bacterial fitness;Body Weight decreased;Bone Marrow;Bone Marrow Cells;Caring;cell type;Cells;Chimera organism;Clinical;Communicable Diseases;Communication;COVID-19 pandemic;cytokine;design;Dinoprostone;Disease;Disease Progression;Dose;Endothelial Cells;Epithelial Cells;epithelial repair;Epithelium;epithelium regeneration;experimental study;Family;Genetic;Genetic Polymorphism;Grant;Granulocyte-Macrophage Colony-Stimulating Factor;Hematopoietic;Host Defense;Human;human disease;IL1R1 gene;Immune;Immune response;Immunity;immunopathology;Impairment;Inflammation;Inflammatory;innate immune mechanisms;Interferons;Interleukin-1;Interleukin-1 alpha;Interleukin-1 beta;Interleukin-1 Receptors;Knock-in;Knock-in Mouse;Knock-out;Knockout Mice;Knowledge;Laboratories;Lung;Lung infections;lung injury;Macrophage;Mediating;member;Morbidity - disease rate;mortality;Mouse Strains;Mus;Mycobacterium tuberculosis;Myeloid Cells;National Institute of Allergy and Infectious Disease;Natural regeneration;neutrophil;Neutrophil Infiltration;Pathogenicity;Pathologic;Patients;PECAM1 gene;pharmacologic;Phenocopy;Play;Predisposition;Preparation;preservation;prevent;Production;progenitor;Progressive Disease;PTPRC gene;Public Health;pulmonary function;Pulmonary Pathology;Pulmonary Tuberculosis;quantitative imaging;Radiation Tolerance;receptor;reconstitution;regeneration following injury;repaired;Reporter;Research;Resistance;Respiratory physiology;response;restraint;Risk;Role;Sampling;self-renewal;Severity of illness;Signal Transduction;single-cell RNA sequencing;stem cell function;Stromal Cells;TACSTD1 gene;Testing;Therapeutic;Tissues;Tuberculosis;tuberculosis immunity;Vaccines;Wasting Syndrome

PROJECT_TITLE: Type II alveolar epithelial cell-intrinsic IL-1 response in protective immunity against tuberculosis

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Clinical Research;Data Science;Eye Disease and Disorders of Vision;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Precision Medicine;Prevention

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS EYE AND EAR INFIRMARY

ORG_STATE: MA

PHR: PROJECT NARRATIVE Glaucoma is a progressive, irreversible optic neuropathy with variable presentation and clinical course and we currently lack the ability to pre-symptomatically distinguish patients at risk of severe and progressive disease from those individuals unlikely to develop glaucoma-related vision loss. Using existing data from two large biobanks, this project will use cutting edge machine learning approaches to define POAG phenotypes aligned with disease subtype and progression, use these to discover novel disease related genetic associations, and test their utility for identifying glaucoma cases in independent cohorts. Ultimately, we aim to develop a precision medicine approach using imaging and genetic features to improve our assessment of disease risk for any individual.

PI_NAMEs: ZEBARDAST, NAZLEE  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Attention;biobank;Blindness;career;career development;case control;Clinical;cohort;Computational Biology;Data;Data Set;Databases;Dedications;demographics;Detection;Development;Development Plans;Diagnosis;Diagnostic tests;Disease;Disease Progression;disorder risk;disorder subtype;DNA;Early treatment;endophenotype;Engineering;Etiology;Eye;Foundations;functional loss;Funding;Fundus;fundus imaging;Genetic;genetic association;Genetic Markers;Genetic Predisposition to Disease;Genetic Risk;genetic risk factor;genetic testing;genetic variant;genome wide association study;genome-wide;genome-wide analysis;genomic data;genomic locus;Genomics;Genotype;Glaucoma;Goals;Growth;Healthcare;Heritability;high intraocular pressure;high risk;Image;Image Analysis;improved;Individual;insight;interest;large-scale imaging data;Learning;learning strategy;Left;Linear Regressions;Logistic Regressions;Machine Learning;machine learning method;macula;Mentors;Meta-Analysis;Methods;multi-ethnic;multidisciplinary;multimodality;Multiomic Data;nerve damage;novel;Optic Nerve;optic nerve disorder;Optical Coherence Tomography;Pathogenesis;Pathway interactions;Patients;Pattern;Phenotype;Physiologic Intraocular Pressure;polygenic risk score;Positioning Attribute;precision medicine;predictive modeling;Primary Open Angle Glaucoma;progression risk;Progressive Disease;Records;Research;Research Personnel;Resources;Retina;Risk;risk prediction;risk variant;ROC Curve;Scanning;Science;Scientist;screening;serial imaging;Series;Severity of illness;statistical and machine learning;statistical learning;structural imaging;supervised learning;System;Techniques;Technology;Testing;Thick;Training;Training Programs;United States National Institutes of Health;unsupervised learning;Variant;Visual Fields;visual optics;Work

PROJECT_TITLE: Glaucoma Risk Prediction Using Machine Learning Integration of Image-Based Phenotypes and Genetic Associations


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

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

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: PROJECT NARRATIVE Alzheimer’s Disease and related dementias (ADRD) take an enormous toll on public health and are more prevalent in Black Americans than White Americans. Structural racism, and its lasting effect on the distribution of neighborhood factors, such as green space, may play a role in cognitive health disparities. The proposed project will investigate the relationships between structural racism, green space exposure, and cognitive health disparities, as well as whether these relationships differ in communities that have undergone gentrification compared to those that have not.

PI_NAMEs: MADRIGANO, JAIME  (contact)

PROGRAM_OFFICER_NAME: BANDIERA, FRANK

PROJECT_TERMS: Affect;Alzheimer's Disease;Alzheimer's disease related dementia;American;Area;Behavior;Black American;Black Populations;Black race;care giving burden;Caregivers;caucasian American;Characteristics;Cities;Clinical;Cognition;Cognitive;Cognitive aging;cognitive function;cognitive impairment no dementia;Color;Communities;contextual factors;Dementia;dementia risk;design;Diabetes Mellitus;Discrimination;Disease;disorder prevention;Disparity;Economics;Educational Status;Elements;Emotional Stress;environmental disparity;environmental justice;Epidemiology;Ethnic Origin;Ethnic Population;experience;Exposure disparity;Exposure to;Family Caregiver;Green space;Health;Health and Retirement Study;health disparity;health equity;Heart Diseases;Hispanic Populations;Impaired cognition;Impairment;improved;Individual;inequitable distribution;Inequity;Intention;Intervention;late life;Link;Literature;Longitudinal Studies;Malignant Neoplasms;Measures;Mediating;Mediator;Mental Health;migration;modifiable risk;Moods;Nature;neighborhood disadvantage;Neighborhoods;Not Hispanic or Latino;Pattern;Persons;Physical activity;physical inactivity;Plants;Policies;Population;Prevalence;prevent;Prevention;Process;psychosocial stressors;Public Health;Race;racial disparity;racial population;Racial Segregation;Regulation;Research;residential segregation;Resources;restoration;Risk;Risk Factors;Role;Sampling;social engagement;Socioeconomic Status;stress reduction;stressor;Structural Racism;Syndrome;Trees;Work

PROJECT_TITLE: Green space and cognitive health: the role of structural racism in environmental and health disparities.


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

ORG_DEPT: OTOLARYNGOLOGY

PHR: PROJECT NARRATIVE Thousands of people in the United States each year suffer permanent voice loss because their voice boxes (larynges) are damaged from nerve injury resulting in vocal fold paralysis and in these cases, we currently have no injectable or minimally invasive options to restore normal laryngeal function. In this application, we explore a novel injectable cellular therapy that promotes nerve recovery and restores function of the voice box (larynx) after laryngeal nerve injury. We believe our findings will completely transform current paradigms for voice restoration in patients who have suffered vocal fold paralysis.

PI_NAMEs: HALUM, STACEY L. (contact);VOYTIK-HARBIN, SHERRY L

PROGRAM_OFFICER_NAME: KOPF, LISA MARIE

PROJECT_TERMS: adduct;adult stem cell;Animal Model;Animals;Aphonia;Atrophic;Attenuated;Autologous;bench to bedside;Biocompatible Materials;biomaterial compatibility;Biomedical Engineering;Biopsy;Cell Therapy;Cells;Cicatrix;Clinic;Clinical;clinical translation;Collaborations;Collagen;collagen scaffold;Communication impairment;cost;Data;Deglutition;delivery vehicle;Denervation;Diameter;Disease;Dysphonia;Electromyography;Etiology;experimental study;Family suidae;FDA approved;Foreign-Body Reaction;functional restoration;Goals;Granulomatous;Human;iatrogenic injury;In Situ;Individual;Injectable;Injections;Injury;innovation;Intratracheal Intubation;Laboratories;Laryngeal muscle structure;Laryngeal neoplasm;Laryngeal Nerves;Laryngoscopy;Larynx;Left;Legal patent;Liquid substance;Medial;Methods;minimally invasive;Modeling;Motion;Motor Endplate;Muscle;Muscle Cells;muscle progenitor cell;muscle reinnervation;Nerve;nerve damage;nerve injury;nerve supply;nerve transection;Nervous System Disorder;neurotrophic factor;novel;novel strategies;Paralysed;Patients;Peripheral nerve injury;Persons;Physicians;Positioning Attribute;Preclinical Testing;pressure;Procedures;Reaction;Recovery of Function;Recurrent Laryngeal Nerve;reinnervation;repaired;restoration;Safety;Saline;Savings;scaffold;Scientist;stem cell therapy;symptomatic improvement;Symptoms;Therapeutic;therapy outcome;Thyroarytenoid Muscle;Time;Translating;Trauma;United States;vocal cord;Voice;Voice Quality

PROJECT_TITLE: Cellular Reinnervation Therapy for Vocal Fold Paralysis

STUDY_SECTION: MFSR

STUDY_SECTION_NAME: Motor Function, Speech and Rehabilitation Study Section[MFSR]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Candidate HIV vaccines for therapy of people who were already infected have met with limited success in clinical trials. One possible explanation for poor results is the tendency of a therapeutic vaccine to further expand anti-HIV immune cells that are already exhausted by chronic infection, rather than eliciting new and more effective immune responses. We want to understand what features of the vaccine and host allow therapeutic vaccination to elicit a superior immune response that may control the HIV virus after daily antiretroviral therapy is stopped.

PI_NAMEs: HARTIGAN-O'CONNOR, DENNIS J. (contact);RUTISHAUSER, RACHEL LENA

PROGRAM_OFFICER_NAME: CRAWFORD, KEITH W

PROJECT_TERMS: Activities of Daily Living;acute infection;Antigens;antiretroviral therapy;Cells;Chronic;chronic infection;Clinical;Clinical Trials;Clone Cells;Cytomegalovirus;DNA;effector T cell;exhaust;Exhibits;Exposure to;Fostering;Frequencies;Goals;HIV;HIV vaccine;Human;Immune;immune function;Immune response;Immune system;Immunodominant Epitopes;improved;Infection;Infection Control;Interruption;Intervention;Intuition;Learning;Link;Literature;Mediating;Memory;Metabolic;metabolomics;multiple omics;next generation;nonhuman primate;novel therapeutics;pathogen;Peptides;Persons;Poxviridae;programs;Property;recruit;Regimen;Research;Residual state;response;restoration;RNA;Sampling;Sampling Studies;Signal Transduction;SIV;Specificity;stem;stemness;success;T cell receptor repertoire sequencing;T cell response;T memory cell;T-Lymphocyte;Testing;Therapeutic;therapeutic vaccine;therapeutically effective;transcription factor;Vaccination;Vaccine Therapy;vaccine trial;Vaccines;vector;Viral;Viremia;Virus

PROJECT_TITLE: Multi-omic understanding of the transformed host T-cell response to HIV following therapeutic vaccination


PHR: The Administrative Core provides organizational structure for the OmiT-HIV program project grant, which seeks to understand and improve immune responses to therapeutic HIV vaccines. If the program is successful then it will lead to better treatments for HIV infection, possibly including treatments that do not require daily ingestion of antiretroviral drugs. Through its administrative and oversight functions, this core will ensure the scientific excellence of the project and its ability to fulfill its aims.

PI_NAMEs: HARTIGAN-O'CONNOR, DENNIS J. (contact)

PROJECT_TERMS: Address;Administrator;Anti-Retroviral Agents;Antigens;Award;Chronic;Clinical Trials;cohort;Collaborations;Communication;Data;Data Analyses;data management;data sharing;Decision Making;Disputes;Elements;Ensure;Environment;experience;Fostering;Funding;Future;Geography;Goals;Grant;HIV;HIV Infections;HIV vaccine;Human;Human Resources;Immune response;Immune system;improved;Ingestion;innovation;International;Medicine;mid-career faculty;multidisciplinary;multiple omics;National Institute of Allergy and Infectious Disease;nonhuman primate;novel strategies;Online Systems;organizational structure;Peer Review;Pharmaceutical Preparations;Process;Program Research Project Grants;programs;Publications;Reporting;Research;Resolution;Resource Sharing;Resources;Sampling;Scientist;somatic cell gene editing;Specialist;Structure;synergism;T cell response;Testing;Therapeutic;United States National Institutes of Health;Vaccine Therapy;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Data Science;Genetics;HIV/AIDS;Human Genome;Immunization;Immunotherapy;Infectious Diseases;Networking and Information Technology R&D (NITRD);Prevention;Vaccine Related

PHR: The Data Management and Analysis Core (DSC) will be part of a project to better understand and improve immune responses to therapeutic vaccines. We will perform and support the statistical analyses that allow meaningful conclusions to be drawn that can improve human health.

PROJECT_TERMS: Address;Affinity;Aftercare;Area;Binding;Bioinformatics;Biological Process;Biometry;Cellular biology;Clinical;Clinical Data;Complex;Custom;Data;Data Analyses;data harmonization;data ingestion;data library;data management;Data Management Resources;data modeling;Data Science;Data Set;data sharing;Data Storage and Retrieval;dimension reduction;Dimensions;Ensure;experience;Flow Cytometry;Goals;Health;HIV;Human;Human Resources;Immune;Immune response;improved;Infection Control;Infrastructure;Ingestion;insight;Interruption;Joints;Kinetics;Mediating;member;Metabolic;metabolomics;Metadata;Modality;Modeling;multidimensional data;multimodal data;multimodality;multiple omics;Nature;nonhuman primate;Online Systems;Outcome;Participant;pathogen;Phenotype;Process;programs;public database;Regimen;repository;Research;Research Personnel;Resolution;Secure;single-cell RNA sequencing;Specificity;Staging;Standardization;Statistical Data Interpretation;Structure;System;T cell receptor repertoire sequencing;T cell response;T-Lymphocyte;Techniques;Testing;therapeutic vaccine;therapy outcome;transcriptome sequencing;vaccine response;Vaccine Therapy;Vaccines;Viral;Viremia;Work

PROJECT_TITLE: Data Management and Analysis Core


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Genetics;HIV/AIDS;Human Genome;Immunization;Immunotherapy;Vaccine Related

PHR: HIV therapeutic vaccines seek to elicit new T cell responses that are long-lived and have the capacity to kill HIV-infected cells in the body. However, little is known about the quality of the T cell responses elicited by leading therapeutic vaccine candidates. In this Project, we will deeply characterize HIV-specific CD8+ T cells before and after vaccination in unique cohorts of people and macaques in order to better understand what kinds of T cells are elicited by the vaccines and how they can be harnessed to control HIV after antiretroviral therapy is stopped.

PROJECT_TERMS: Activities of Daily Living;Adenoviruses;Aftercare;Alleles;Anti-viral Response;Antigens;antiretroviral therapy;Binding;Blinded;Blood;Blood specimen;CD8-Positive T-Lymphocytes;Cells;Cellular Assay;Chad;Clinical Data;Clinical Trials;clinically relevant;Clone Cells;cohort;Data;DNA;efficacy evaluation;Elements;Enrollment;Epitopes;exhaustion;Exhibits;experience;Flow Cytometry;Genetic Transcription;high dimensionality;HIV;Home;Human;Immunity;Immunology;improved;Individual;Interferon Type II;Interruption;Kinetics;lymph nodes;Macaca;Measurable;Measurement;Memory;Modality;multimodality;multiple omics;Participant;peripheral blood;Persons;Phenotype;Placebos;Proliferating;Property;Randomized;Receptor Signaling;recruit;Regimen;Reporting;Residual state;response;Route;Sampling;Site;SIV;Specificity;Structure;System;T cell receptor repertoire sequencing;T cell response;T memory cell;T-Cell Receptor;T-Lymphocyte;Testing;therapeutic candidate;therapeutic vaccine;transcriptome sequencing;Vaccination;vaccine candidate;vaccine delivery;Vaccine Therapy;Vaccinee;Vaccines;Viral;Viral Load result;Virus

PROJECT_TITLE: Project 1


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Obesity;Prevention;Sleep Research

ORG_CITY: SALT LAKE CITY

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE Chronic sleep loss and short sleep duration are epidemic in modern society, representing an important public health issue. The goal of this project is to identify biomarkers that link adverse cardiometabolic risk with habitual short sleep duration and to determine if sleep extension reverses such risk. We expect these findings will help identify people with elevated cardiometabolic risk due to habitual short sleep duration and could improve our ability to quantify, track, and reduce an individual’s risk of type 2 diabetes over time.

PI_NAMEs: DEPNER, CHRISTOPHER MICHAEL (contact)

PROGRAM_OFFICER_NAME: TATAW-AYUKETAH, GLADYS OROCK

PROJECT_TERMS: Acute;adequate sleep;Adult;adult obesity;Aging;American;Area;Automobile Driving;Beds;Biological Assay;Biological Markers;biomarker identification;biomarker signature;candidate marker;candidate validation;Cardiometabolic Disease;cardiometabolic risk;Ceramides;Chronic;Clinic;Clinical;clinical risk;Controlled Study;Data;design;Development;Diabetes Mellitus;diabetes risk;Diet;Economic Burden;Effectiveness;emergency service responder;Epidemic;epidemiologic data;Epidemiology;epidemiology study;experimental study;Foundations;Future;Glucose Clamp;Goals;Health;Health Benefit;Health Personnel;Home;Hour;Hyperinsulinism;impaired glucose tolerance;Impairment;improved;Incidence;Individual;Insulin Resistance;insulin sensitivity;Intervention;Knowledge;Laboratories;Laboratory Study;Link;Lipids;Maintenance;Metabolism;metabolomics;Military Personnel;Modernization;molecular marker;Monitor;Non-Insulin-Dependent Diabetes Mellitus;novel;Overweight;Participant;Pathway Analysis;Pathway interactions;Persons;Physical activity;Plasma;Prediabetes syndrome;Prevention;primary outcome;Public Health;Quality of life;Randomized;Randomized, Controlled Trials;Recommendation;Reporting;Risk;Risk Factors;risk prediction;Risk Reduction;ROC Curve;Safety;Sleep;Sleep Deprivation;Societies;Sphingolipids;Students;Sum;Testing;Thinness;Time;Translating;United States;Visit;Work

PROJECT_TITLE: Biomarkers of Habitual Short Sleep and Related Cardiometabolic Risk

STUDY_SECTION: HSDO

STUDY_SECTION_NAME: Human Studies of Diabetes and Obesity Study Section[HSDO]


NIH_SPENDING_CATS: Biotechnology;Genetics;HIV/AIDS;Human Genome;Immunization;Immunotherapy;Infectious Diseases;Prevention;Vaccine Related

PHR: This project will examine how an HIV-infected person’s metabolism can affect their immune response to a therapeutic vaccine. We seek to develop techniques for altering metabolism either systemically or locally, at the site of therapeutic-vaccine administration, to make responses better. If successful then this project will explain why some individuals respond well to therapeutic vaccines and others do not.

PROJECT_TERMS: 2019-nCoV;Affect;Aftercare;Amino Acids;arginase;Arginine;Catabolism;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Physiology;Cells;Cellular Metabolic Process;Clinical Trials;Cohort Studies;Data;design;detection of nutrient;Energy-Generating Resources;Enzymes;exhaust;experimental study;Failure;FRAP1 gene;Generations;HIV;Human;human data;Immune response;Individual;Infection;inhibitor;Interruption;Jaw;Link;Literature;Macaca;Macaca mulatta;Measures;Mediating;Memory;Metabolic;Metabolic Control;Metabolic Pathway;metabolic profile;Metabolism;metabolomics;mTOR inhibition;multiple omics;nonhuman primate;Nucleocapsid;Nutrient;Pathway interactions;Pattern;Persons;Plasma;Population;Positioning Attribute;pre-clinical;Property;recruit;Regimen;Regulation;response;restraint;Route;Sampling;sensor;Sirolimus;Site;SIV;SIV Vaccines;stem;success;System;T cell differentiation;T cell response;T cell therapy;T memory cell;T-Cell Development;T-Lymphocyte;T-Lymphocyte Subsets;Techniques;Testing;Therapeutic;therapeutic vaccine;transcriptome sequencing;Vaccinated;Vaccination;Vaccine Therapy;vaccine trial;Vaccinee;Vaccines;Variant;vector vaccine;Viremia;Virus;Virus Replication

PROJECT_TITLE: Project 2


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

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: NARRATIVE This study is designed to help improve the care of SGM with AD/ADRD in LTSS by conducting a rigorous study of the policies of LTSS agencies in Minnesota and by training the state’s LTSS workforce in SGM culturally responsive care. The study of policy will inform whether LTSS agencies need regulation or have already adopted SGM appropriate policies. The randomized controlled trial will rigorously test the effects of an in- person versus an online training program on improving SGM culturally responsive care.

PI_NAMEs: ROSSER, B R SIMON  (contact);SHIPPEE, TETYANA P.

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: Address;Adopted;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Area;arm;Assisted Living Facilities;Attention;Attitude;Caring;Certification;cisgender;Client;comparative effectiveness study;Control Groups;Data Collection;dementia care;design;Discrimination;E-learning;Educational Curriculum;Educational Intervention;Effectiveness;efficacy evaluation;Environment;evidence base;Evidence based intervention;Family member;follow-up;Fright;Funding;Gender Identity;gender minority health disparity;Health;health care availability;health care service;health disparity;Heterosexuals;Hostility;human old age (65+);Human Resources;Impaired cognition;improved;Individual;Inferior;Instruction;Intake;Intervention;Knowledge;Lesbian Gay Bisexual;Licensing;Long-Term Care;Long-Term Effects;Marketing;Medicare/Medicaid;Methods;Minnesota;Minority;Modeling;Nursing Homes;older adult;online course;online intervention;online version;Outcome;Participant;peer;Persons;Policies;Policy Analysis;Population;Prevalence;Quality of life;Randomized, Controlled Trials;Regulation;Religion;Research;Risk;Rural;Safety;satisfaction;Service provision;Services;Sex Orientation;Sexual and Gender Minorities;skills;Social Work;sound;Statutes and Laws;Testing;Training;Training Programs;Training Support;transgender;United States National Institutes of Health;Violence;Waiting Lists

PROJECT_TITLE: Training the Long-Term Services and Supports Dementia Care Workforce in Provision of Care to Sexual and Gender Minority Residents

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HDM-V(02)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PHR: Alzheimer's disease (AD) and AD-related diseases such as Amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) are incurable. Proposed studies will test function of GDE2 as a new pathway that prevents neuronal cell-cycle re-entry and nuclear envelope/nuclear pore complex breakdown, two causal mechanisms of neurodegeneration important in AD and ALS-FTD. Discoveries made will generate new understanding of disease mechanisms and have potential to identify new targets for therapeutic intervention.

PI_NAMEs: LLOYD, THOMAS E.;SOCKANATHAN, SHANTHINI  (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Adult;Age;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Animals;Antimitotic Agents;Automobile Driving;Autopsy;Biological Assay;Biological Models;C9ORF72;Cell Cycle;Cell Cycle Inhibition;Cell membrane;Cells;cellular pathology;Cessation of life;Cyclin D1;design;Development;Disease;Drosophila cyclin D;Drosophila genus;effective therapy;Embryonic Development;Enzymes;Event;Excision;Exhibits;Failure;fly;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;G1/S Transition;Genes;Genetic;Genetic study;Genetic Suppression;glycerophosphodiester phosphodiesterase;Glycosylphosphatidylinositols;GPI Membrane Anchors;Human;human disease;human induced pluripotent stem cells;Huntington Disease;Impairment;Induced Neurons;Induced pluripotent stem cell derived neurons;insight;Knockout Mice;Lamin Type A;Life;Link;Maintenance;Mediating;Membrane;Mitosis;Mitotic;Mitotic Cell Cycle;Modeling;Molecular;Mus;Nerve Degeneration;Nervous System;Neurodegenerative Disorders;neuron loss;neuronal survival;Neurons;new therapeutic target;novel;Nuclear Envelope;Nuclear Pore Complex;Nuclear Pore Complex Proteins;nucleocytoplasmic transport;Outcome;Pathogenesis;Pathology;Pathway interactions;Patients;Peptide Initiation Factors;Physiological;postmitotic;preservation;prevent;Process;progenitor;progressive neurodegeneration;protein transport;Proteins;Regulatory Pathway;Reporter;segregation;Signal Transduction;Spatial Distribution;Specificity;stem cells;System;Testing;Therapeutic Intervention;Tissues;trafficking;transcriptome sequencing;Visualization;WNT Signaling Pathway;Work

PROJECT_TITLE: Neuronal cell-cycle re-entry and neurodegeneration

STUDY_SECTION: SYN

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


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Childhood Injury;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Pediatric;Physical Injury - Accidents and Adverse Effects;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Suicide;Violence Research;Youth Violence;Youth Violence Prevention

ORG_NAME: UNIVERSITY OF NEW HAMPSHIRE

ORG_STATE: NH

PHR: PROJECT NARRATIVE The proposed research is highly relevant to public health because it will provide critical data on the pathways to intent to act and leverage points for influencing actual bystander behavior among those who report knowing someone at risk for self-directed violence (SDV), including how youth perceive the outcomes of their actions. Importantly, this study will also identify how exposure to SDV may be differentially impacting the helping behaviors and the impact of such behaviors over time for sexual and gender minority as well as racial/ethnic minority populations, information key to designing more helpful suicide prevention strategies. As a result, we would expect decreased morbidity from SDV, improved quality of life for SDV youth and their friends and families, and a widespread reduction in medical costs associated with SDV.

PI_NAMEs: BANYARD, VICTORIA L;MITCHELL LEMA, KIMBERLY J (contact)

PROGRAM_OFFICER_NAME: ROONEY, MARY

PROJECT_TERMS: Address;Adolescent and Young Adult;Adult;Affect;Age;Attention;Attitude;Awareness;Behavior;behavior change;Black race;Cessation of life;Characteristics;Cognitive;cohort;contagion;Data;design;Development;Discrimination;Disparity;early adolescence;Ensure;Environment;ethnic minority;ethnic minority population;experience;Exposure to;Family;Feeling;Feeling suicidal;Friends;Future;Gatekeeping;gender minority group;gender minority youth;health disparity;Helping Behavior;improved;Inequality;Injury;innovation;Interpersonal Violence;Intervention;Knowledge;Longitudinal Studies;marginalization;Medical Care Costs;Mental Depression;Mental Health;minority children;Minority Groups;Modeling;Morbidity - disease rate;non-suicidal self injury;Outcome;Participant;Pathway interactions;peer;peer victimization;Persons;Play;Prevention strategy;programs;prospective;Public Health;Quality of life;racial minority;racial minority population;recruit;Reporting;Research;Risk;Risk Factors;Role;Sampling;Self Direction;Self-Injurious Behavior;Sexual and Gender Minorities;sexual minority group;sexual minority youth;social;social media;Subgroup;substance use;success;suicidal behavior;suicidal morbidity;Suicide;Suicide attempt;Suicide prevention;suicide rate;Surveys;Thinking;Time;Training;Training Programs;trauma symptom;trend;Violence;violence exposure;violence prevention;Work;young adult;Youth;youth violence

PROJECT_TITLE: Understanding Bystanders for Self-Directed Violence Prevention: A Prospective National Study Highlighting Marginalized Youth and Young Adults

STUDY_SECTION: CIHB

STUDY_SECTION_NAME: Community Influences on Health Behavior Study Section[CIHB]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Disability Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Mental Illness;Schizophrenia;Serious Mental Illness;Social Determinants of Health

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Mental disorders are among the leading causes of disability and morbidity worldwide, including Brazil, where despite having a comprehensive network of publicly-funded, free, community-based mental health treatment, it is estimated that only 26% of people with psychiatric conditions successfully connect to community-based care. We hypothesize that the successful adaptation and implementation of an evidence-based model of peer support to Brazilian culture, will contribute to enhanced levels of engagement, improved continuity of care, and improvements in quality of life and wellbeing among persons living with SMI in Brazil. After this study, we will have established the feasibility, acceptability, safety and tolerability, of adapting a low-cost, culturally-responsive, evidence-based intervention to improve post-acute supportsfor people with SMI who access community mental health treatment.

PI_NAMEs: BELLAMY, CHYRELL DENISE;O'CONNELL, MARIA J (contact);ONOCKO-CAMPOS, ROSANA TERESA

PROGRAM_OFFICER_NAME: CUBILLOS, LEONARDO

PROJECT_TERMS: Accident and Emergency department;Acute;Administrator;Affect;Beds;behavioral health;Brazil;Caring;Clinical Trials;Collaborations;Communities;community based care;Community Mental Health Services;Community Services;Continuity of Patient Care;cost;Country;COVID-19;Crowding;design;Development;disability;Discrimination;economic disparity;effectiveness trial;Emergency Situation;Environment;evidence base;Evidence based intervention;Family member;follow-up;Fostering;Funding;Goals;healing;Health Services;Healthcare;Hospitals;Implementation readiness;implementation science;implementation trial;improved;improved outcome;Income;innovation;innovative technologies;International;Intervention;Investigational Therapies;Life;Lived experience;low and middle-income countries;Mediator;Mental disorders;Mental Health;Mental Health Services;Methods;Modeling;Morbidity - disease rate;National Institute of Mental Health;Natural Source;Outcome;Pathway interactions;peer;peer support;Personal Satisfaction;Persons;physical conditioning;Political Factor;poor communities;Population;psychosocial;Public Health;Quality of Care;Quality of life;Recommendation;Recovery;Research;Research Priority;Research Support;Resource-limited setting;Safety;scale up;Service delivery model;Services;severe mental illness;social;social stigma;Societies;Structure;symptom management;System;Translating;Translations;Universities;Work

PROJECT_TITLE: Adaptation and Implementation of Peer Support to Optimize Engagement and Outcomes for People with Serious Mental Illness in Campinas, Brazil


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

ORG_CITY: BLOOMINGTON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

PHR: PROJECT NARRATIVE Social connectedness is a promising target for slowing the progression of Alzheimer’s disease (AD). The current proposal uses cutting-edge methods to determine how aging disrupts a key mechanism underlying social connectedness – social cognition. The project leverages the complementary expertise of an interdisciplinary research team to advance our understanding of healthy aging and AD.

PI_NAMEs: BETZEL, RICHARD F;KRENDL, ANNE CATHERINE (contact)

PROGRAM_OFFICER_NAME: STOECKEL, LUKE

PROJECT_TERMS: Address;Adult;Affect;Age;age difference;age related;age related changes;Aging;aging related;Alzheimer's Disease;Behavior;Brain;Brain region;Clinical;Cognitive;Cognitive aging;Cognitive deficits;cognitive function;cognitive task;Collection;Communication;Data;effective intervention;Functional Magnetic Resonance Imaging;Goals;healthy aging;improved;innovation;insight;Interdisciplinary Study;interest;Intervention;Knowledge;life span;Measures;mental state;Methods;Nature;neglect;neuroimaging;neuromechanism;Neurosciences;novel;older adult;pathological aging;Performance;Persons;Population;Poverty;Process;Research;Rest;Sampling;social;Social Behavior;social cognition;Social Controls;Social Interaction;Social Network;social neuroscience;social relationships;Stimulus;Structure;Task Performances;theory of mind;Weight;Work;young adult

PROJECT_TITLE: Dynamic approaches to understanding social cognitive aging: A social network neuroscience approach

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


NIH_SPENDING_CATS: Clinical Research;Kidney Disease;Machine Learning and Artificial Intelligence;Organ Transplantation;Patient Safety;Precision Medicine;Prevention;Transplantation

ORG_DEPT: SURGERY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE Immunosuppression is the key intervention that makes kidney transplantation possible, while it is also a significant risk factor for infection, cancer, and cardiovascular diseases, the top 3 causes of mortality among kidney transplant recipients. Immunosuppression individualization will improve the health and longevity of kidney transplant recipients by maximizing the protection against acute rejection while minimizing immunosuppression-related side effects; however, the scientific evidence to guide this practice is severely lacking. This grant will allow us to lay the groundwork for an evidence-based, patient-centered, and clinically relevant framework for immunosuppression individualization.

PI_NAMEs: BAE, SUNJAE  (contact)

PROGRAM_OFFICER_NAME: RANKIN, TRACY L

PROJECT_TERMS: Accounting;Acute;Address;American;analytical method;Antibodies;Benefits and Risks;Biometry;Cardiovascular Diseases;career development;Caring;Cessation of life;Clinical;clinical practice;clinically relevant;Cluster randomized trial;Communities;computerized tools;Consensus;Data;Data Set;Decision Analysis;design;disability weights;Doctor of Philosophy;efficacy outcomes;Epidemiology;Equilibrium;evidence base;experience;feasibility testing;Foundations;Future;Goals;gradient boosting;graft failure;Grant;Health;high risk;Immunosuppression;implementation science;improved;Individual;Infection;infection risk;insight;Intervention;Interview;Kidney Transplantation;Knowledge;Longevity;Machine Learning;machine learning prediction;Malignant Neoplasms;Measures;Medical Education;medical schools;Mentored Research Scientist Development Award;Mentors;Mentorship;Methodology;Methods;Modeling;mortality;multidisciplinary;Nephrology;Non-Insulin-Dependent Diabetes Mellitus;novel;Operative Surgical Procedures;Outcome;outcome prediction;Paired Comparison;Paper;participant interview;patient oriented;patient oriented research;Patient Recruitments;Patients;personalized predictions;personalized risk prediction;Population;population health;Positioning Attribute;predictive modeling;prevent;professor;Protocols documentation;Public Health Schools;Published Comment;Quality-Adjusted Life Years;Regimen;Research;Research Methodology;Research Training;Respondent;response;Risk;Risk Factors;risk prediction;risk prediction model;Risk-Benefit Assessment;safety outcomes;Scholarship;Science;side effect;skills;Societies;Statistical Computing;Steroids;Subgroup;Surveys;Techniques;tool;Training;Transplant Recipients;Transplant Surgeon;Transplantation;Universities;Variant;Withdrawal;Work

PROJECT_TITLE: Individualized Immunosuppression for Kidney Transplant Recipients

STUDY_SECTION: DDK

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


ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Impaired left ventricular relaxation or compliance, commonly referred to as diastolic dysfunction, is associated with the progression to heart failure with preserved ejection fraction, a devastating syndrome with poor prognosis for which limited therapeutic interventions currently exist. Pharmacological inhibition of histone deacetylases (HDACs), epigenetic enzymes that regulate chromatin-dependent signal transduction in the development of heart failure, have shown promise pre-clinically in the setting of diastolic dysfunction, however little is known regarding the HDAC isoform specificity and molecular mechanisms regulating this cardioprotection. The present proposal will leverage innovative small molecule inhibitors, genetics-based strategies for cell-specific gene ablation, and the integration of multifaceted state-of-the-art epigenomics and bioinformatics techniques to elucidate the cellular specificity and molecular mechanisms of HDAC inhibitor efficacy in diastolic dysfunction.

PI_NAMEs: TRAVERS, JOSHUA  (contact)

PROGRAM_OFFICER_NAME: WANG, WAYNE C

PROJECT_TERMS: Ablation;Animals;Architecture;Attenuated;Award;Binding Proteins;biobank;Bioinformatics;Biology;Cardiac;cardioprotection;Cardiovascular Diseases;cell type;Cells;Characteristics;Chromatin;Clinical;clinically relevant;Colorado;Complement;Complex;Core Facility;coronary fibrosis;Data;Death Rate;Deposition;Development;Dose Limiting;EFRAC;Environment;Enzymes;Epigenetic Process;epigenetic regulation;epigenomics;Extracellular Matrix;Family;Fibroblasts;Flow Cytometry;Foundations;Functional disorder;Future;Galectin 1;Genes;Genetic;genetic corepressor;Genetic Transcription;genome-wide;Genomics;Goals;HDAC1 gene;Heart;Heart failure;Hematology;Histone Acetylation;Histone Deacetylase;Histone Deacetylase Inhibitor;Human;Impairment;Inflammatory;inflammatory modulation;Inflammatory Response;Infrastructure;inhibitor;Injury;innovation;Institution;International;knock-down;Knowledge;Laboratories;Left;Macrophage;Mediating;Medical;Mentors;Mentorship;Molecular;mouse model;Mus;Myofibroblast;next generation sequencing;novel;novel therapeutic intervention;Pathogenesis;Pathway interactions;patient population;Patients;Pharmaceutical Preparations;pharmacologic;Phase;Polysaccharides;Population;pre-clinical;preservation;pressure;Process;Prognosis;Property;Protein Isoforms;Proteomics;recruit;Relaxation;Research;Research Personnel;Resolution;Risk;Role;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;skill acquisition;Small Interfering RNA;small molecule inhibitor;Solid;Specificity;standard of care;success;Syndrome;Techniques;Technology;Testing;Therapeutic;Therapeutic Intervention;Toxic effect;Training;transcriptome sequencing;transcriptomics;Treatment Efficacy;treatment strategy;Universities;Ventricular

PROJECT_TITLE: Elucidating the Molecular Mechanisms and Cellular Specificity of HDAC Inhibitor Efficacy in Diastolic Dysfunction

STUDY_SECTION: MTI

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


NIH_SPENDING_CATS: Complementary and Integrative Health;Dietary Supplements;Eye Disease and Disorders of Vision;Genetics;Natural Products;Neurodegenerative;Neurosciences;Nutrition;Rare Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: PHARMACOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: NARRATIVE Progressive degeneration of photoreceptors triggered by inherited destabilizing mutations in the rhodopsin (RHO) gene and consequently activated cellular stress response triggering apoptosis cause retinitis pigmentosa (RP), currently an incurable blinding disease. Therapeutic approaches to correct these impartments focus on the development of pharmacological chaperones that stabilize Rho to prevent this retinopathy. We propose here comprehensive biochemical, structural, and animal studies to develop a novel therapeutic remedy to counter RP pathology and prevent vision loss.

PI_NAMEs: JASTRZEBSKA, BEATA  (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: 11 cis Retinal;Adjuvant;analog;Animals;Apoproteins;Apoptosis;Architecture;BCL2 gene;Binding;Binding Sites;Biochemical;Biological Availability;biophysical analysis;Blindness;Cell Culture Techniques;Cell Death;Cell Physiology;Cells;Cellular Stress;Cessation of life;chromophore;Clinical Research;combat;Complex;Crystallography;Cytoprotection;Data;design;Development;Dietary Flavonoid;Disease;disease phenotype;effective therapy;effectiveness evaluation;Enhancers;Equilibrium;Eye diseases;fitness;Flavonoids;G-Protein-Coupled Receptors;Gene Expression;Genes;Genetic;Health;high throughput screening;Hybrids;Impairment;improved;In Vitro;in vivo;Inherited;Inhibition of Apoptosis;inhibitor;injured;invention;Knock-in;Knock-out;Knowledge;Learning;Libraries;Light;Link;Mass Spectrum Analysis;Mediating;Membrane;Modeling;Molecular;Molecular Chaperones;Molecular Target;Morphology;mouse model;Mus;mutant;Mutation;mutation screening;Natural regeneration;neuroprotection;novel;novel therapeutics;Opsin;Pathogenicity;Pathologic;Pathology;Patients;pharmacologic;Phenotype;photoreceptor degeneration;Photoreceptors;Phototransduction;prevent;Quercetin;Reporting;Research Personnel;response;Retina;Retinal Degeneration;Retinal Diseases;Retinitis Pigmentosa;Rhodopsin;Role;Signal Transduction;small molecule;small molecule inhibitor;Stress;Techniques;Testing;Therapeutic;Therapeutic Effect;therapeutically effective;trafficking;Transcriptional Regulation;treatment effect;Variant;Vertebral column;Vision;Visual System

PROJECT_TITLE: Novel neuroprotective activities of flavonoids against retinal degenerative diseases

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Vaccines;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Immunization;Infectious Diseases;Influenza;Mental Health;Pneumonia and Influenza;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Vaccine Related

ORG_CITY: SANTA MONICA

ORG_NAME: RAND CORPORATION

PHR: PROJECT NARRATIVE Vaccination rates vary considerably by race/ethnicity with rates for Whites at least six times higher than for any other group. Many factors contribute to these inequities in vaccination rates including differences in vaccine acceptance and intention, and related variability in social behavioral norms, knowledge, risk perception, trust, and structural barriers. This research will examine whether an intervention that is delivered by community health workers to provide education, help with behavior change, and assistance with navigating barriers to increase equal access to vaccination, is effective in increasing vaccination rates.

PI_NAMEs: LARA, MARIELENA  (contact);MEREDITH, LISA SEIDEL;TOBIN, JONATHAN N.

PROGRAM_OFFICER_NAME: JONES, NANCY LYNNE

PROJECT_TERMS: Address;Adult;Affect;Anxiety Disorders;Asthma;Attitude;Awareness;Behavior;behavior change;Behavior Therapy;Behavioral;Behavioral Model;bilingualism;Case Management;Characteristics;Chronic;Chronic Disease;Clinical;Color;Communicable Diseases;Communities;community advisory board;community based participatory research;community engagement;Community Health Aides;Community Healthcare;community organizations;comparison intervention;Conscious;contextual factors;COVID-19;COVID-19 vaccination;COVID-19 vaccine;Data;Decision Making;design;Diabetes Mellitus;Education;Educational Materials;effective intervention;Effectiveness of Interventions;efficacy evaluation;efficacy testing;Emotional;Equilibrium;Equity;ethnic minority;ethnic minority population;Ethnic Origin;Ethnic Population;evidence base;Exhibits;experience;Federally Qualified Health Center;follow-up;formative assessment;Goals;Habits;Health;health care service;Health Services Accessibility;Healthcare;Hypertension;improved;Individual;Inequity;Influenza;Influenza vaccination;Information Dissemination;Intention;Intervention;intervention effect;Interview;Knowledge;Language;Link;literacy;Measures;Mediating;Mediator;Medical;meetings;Mental Depression;Mental disorders;Methods;Modeling;Modification;Motivation;multi-component intervention;New Jersey;New York City;Not Hispanic or Latino;Obesity;Participant;Patient Outcomes Assessments;Patients;Physical Capacity;Physical environment;poor communities;Population;population based;Population Heterogeneity;Post-Traumatic Stress Disorders;Poverty;Primary Care;primary outcome;Psyche structure;psychoeducation;psychologic;Race;racial minority;racial minority population;racial population;Randomized;Randomized, Controlled Trials;Research;Resources;response;Risk;Risk Assessment;risk perception;Role;secondary outcome;skills;social;Social Environment;social health determinants;social norm;Spanish/English;structural determinants;Structural Racism;System;Techniques;Telephone;transmission process;treatment as usual;Treatment Efficacy;Treatment outcome;Trust;Uninsured;uptake;Vaccinated;Vaccination;vaccine acceptance;vaccine access;vaccine hesitancy;Vulnerable Populations;World Health Organization

PROJECT_TITLE: Impact of a Community Care Intervention to Address Inequities in COVID-19 and Influenza Vaccination Among Adults Suffering from Disproportionate Chronic Disease

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


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Microbiome;Substance Misuse

ORG_CITY: GREENSBORO

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF NORTH CAROLINA GREENSBORO

PHR: PROJECT NARRATIVE Alcohol abuse impairs the intestinal mucosal immune system which plays a critical role in maintaining the equilibrium of a highly complex gut ecosystem. This project is to investigate the mechanisms of how alcohol abuse impairs the intestinal mucosal immune function and induces dysbiosis in the development of alcoholic liver disease. The goal of this project is to explore molecular targets for developing therapeutic interventions.

PI_NAMEs: ZHOU, ZHANXIANG  (contact)

PROGRAM_OFFICER_NAME: WANG, JOE

PROJECT_TERMS: Acetaldehyde;Acute;Alcohol abuse;Alcohol consumption;alcohol exposure;Alcoholic Hepatitis;Alcoholic Liver Cirrhosis;Alcoholic Liver Diseases;Alcohols;Aldehydes;Antigens;Attenuated;Bacteria;Biological Assay;Caco-2 Cells;Cell Culture Techniques;Cell Differentiation process;Cell surface;Cells;Chronic;Cirrhosis;Complex;Consumption;Defect;Dendritic cell activation;Dendritic Cells;Development;Disease;Distal;dysbiosis;Ecosystem;Endotoxemia;Engineering;Equilibrium;FDA approved;feeding;Functional disorder;Funding;gastrointestinal epithelium;Goals;gut homeostasis;gut microbiota;gut-liver axis;Heavy Drinking;host microbiota;Hypoxia;IL17 gene;Immune;immune function;Immune response;Immunity;Impairment;improved;inhibitor;Interferon Type II;Interferons;Interleukin-12;interleukin-22;interleukin-23;intestinal epithelium;Intestinal Mucosa;Intestines;IRF4 gene;Knockout Mice;Lactobacillus reuteri;Lamina Propria;Lesion;Liver;liver inflammation;liver injury;Lymph;Mediating;microbial;microbiota;migration;Molecular;Molecular Target;mouse model;Mucosal Immune System;Mus;novel;Oral Administration;Organ;organ injury;oxidation;pathogen;Pathogenesis;Pathway interactions;Pattern;Pharmaceutical Preparations;Physiological;Play;Production;Proteomics;receptor;response;Role;Signal Pathway;Signal Transduction;simple steatosis;STAT1 gene;STAT3 gene;Succinates;T-Lymphocyte;Testing;Th1 Cells;Therapeutic;Therapeutic Intervention;Tissues

PROJECT_TITLE: Aldehydes in Alcohol-Induced Organ Injury

STUDY_SECTION: XNDA

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


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Genetics;Neurodegenerative;Neurosciences;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Schwann cells not only form myelin that is critical for nervous system development, but they also perform several pro-regenerative roles after peripheral nerve injury. This proposal will characterize transcriptional and epigenomic switches required for reprogramming Schwann cells after peripheral nerve injury, and will elucidate the role of hedgehog signaling in nerve injury.

PI_NAMEs: AWATRAMANI, RAJESHWAR B;SVAREN, JOHN P (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Acceleration;Action Potentials;Aging;Automobile Driving;Axon;axon regeneration;Binding;Cell Reprogramming;cell type;Central Nervous System;chemotherapy;Chronic;Communicable Diseases;Complex;Denervation;Deubiquitination;Development;Diabetic Neuropathies;Disease;Distal;Enhancers;Ensure;epigenomics;Gene Activation;Gene Expression;gene network;Genes;Genetic Diseases;Genetic Transcription;Goals;histone modification;Histones;Homeostasis;Impairment;Inflammation;Injury;insight;jun Oncogene;Knock-out;Laboratories;Mediating;Metabolic;Methylation;Modeling;Mus;Myelin;myelination;Natural regeneration;Nerve;Nerve compression syndrome;nerve damage;nerve injury;Nerve Regeneration;nerve repair;Nervous System;nervous system development;Nervous System Disorder;Neural Crest;neurodevelopment;neuronal survival;neurotrophic factor;novel;Pathway interactions;Peripheral nerve injury;peripheral nerve regeneration;Peripheral Nerves;Peripheral Nervous System;Play;Polycomb;PRC1 Protein;prevent;Process;programs;Proteins;regeneration potential;regenerative;Regulation;remyelination;repaired;Repression;Resources;response;response to injury;Role;Schwann Cells;severe injury;SHH gene;Signal Transduction;smoothened signaling pathway;stem cell niche;Techniques;Testing;Therapeutic;Time;tool;transcription factor;Transcription Factor AP-1;Trauma;ubiquitin isopeptidase;Ubiquitination;Work

PROJECT_TITLE: Schwann Cell Reprogramming after Nerve Injury

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Nanotechnology

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: Project Narrative Being able to see and measure enzyme activity in the complex context of live animals would enable entirely new investigations into the role these critical proteins play in health and disease. Seeing through the animal tissue requires using near infrared or, more recently, short-wave infrared wavelengths of light that penetrate tissues with minimal scattering, yielding very clear luminescent images. This project will use bioluminescent enzymes (luciferases) and semiconductor quantum dots to generate self-illuminating, enzyme-responsive, SWIR-emitting contrast agents optimized to non-invasively produce bright, clear images of enzyme activity in the context of the living animal.

PI_NAMEs: DENNIS, ALLISON MARIE (contact)

PROGRAM_OFFICER_NAME: ATANASIJEVIC, TATJANA

PROJECT_TERMS: absorption;animal tissue;Animals;attenuation;Biocompatible Materials;Biological Markers;Biological Process;Bioluminescence;bioluminescence imaging;Biosensor;Body System;Calibration;Cell Line;Cell surface;Cells;Characteristics;Cirrhosis;Communities;Complex;Contrast Media;design;Detection;Development;Disease;Disease Progression;Energy Transfer;enzyme activity;Enzymes;Fibrosis;Fluorescence;fluorophore;Functional disorder;hazard;Health;Hepatitis;high resolution imaging;Image;imager;Imaging Phantoms;imaging potential;imaging probe;improved;In Vitro;in vitro testing;in vivo;in vivo imaging;Investigation;Ionizing radiation;Light;Liver;Liver Cirrhosis;Liver diseases;Luciferases;Magnetic Resonance Imaging;Maps;Matrix Metalloproteinases;Measurement;Measures;Methods;Molecular;Morphology;mouse model;Noise;Optics;Organ;Organism;Penetration;Peptides;Physiological Processes;Physiology;Play;pre-clinical;Primary carcinoma of the liver cells;protein aminoacid sequence;Proteins;Quantum Dots;ratiometric;Reporting;Research;Resolution;Role;Semiconductors;sensor;Short Waves;Signal Transduction;Surface;System;Techniques;Testing;Tissue imaging;tissue phantom;Tissues;virtual;Visualization

PROJECT_TITLE: In Vivo Mapping of Enzyme Activity using SWIR-emitting, Self-illuminating Quantum Dot Sensors

STUDY_SECTION: NANO

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it could reveal strategies to target the combinatorial control of Notch-dependent promoter and enhancer elements in T-cell acute lymphoblastic leukemia, a cancer affecting both children and adults and in which Notch inhibitors have been proven to be too toxic in early clinical trials. We discovered that ETS1 promotes enucleation of many oncogenic transcription factor players at Notch-responsive elements. In this proposal, we will learn how these players cooperatively interact and find ways to disrupt these interactions to target oncogenic Notch transcriptional programs and circumvent the toxicity of pan-Notch inhibitors.

PI_NAMEs: CHIANG, MARK Y (contact)

PROGRAM_OFFICER_NAME: READ-CONNOLE, ELIZABETH LEE

PROJECT_TERMS: Acute T Cell Leukemia;acute T-cell lymphoblastic leukemia cell;Adult;Affect;Binding;Cell Proliferation;cell type;Cells;chemotherapy;Child;Childhood;Chromatin;Chromatin Remodeling Factor;Clinical Trials;cofactor;Collaborations;combat;combinatorial;Complex;Data;deprivation;Development;DNA amplification;DNA Repair;Dose Limiting;Drosophila genus;early phase clinical trial;Elements;Enhancers;ETS1 gene;Gene Expression;Genetic Enhancer Element;Genetic Transcription;genome-wide;Goals;Health;human model;Impairment;inhibitor;innovation;intestinal homeostasis;Intestines;Knowledge;Label;Learning;leukemia;leukemogenesis;Link;Maintenance;Malignant Neoplasms;Methods;Modeling;mouse model;Names;notch protein;NOTCH1 gene;Oncogenes;Oncogenic;Oxidative Phosphorylation;Pathway interactions;Patients;Polymerase;programs;Proliferating;promoter;Public Health;recruit;Regulatory Element;Repression;Research;Response Elements;Role;scaffold;Signal Transduction;Site;stem;stem cells;T-Cell Activation;T-Lymphocyte;targeted agent;targeted treatment;Testing;Therapeutic;therapeutic target;therapy development;time use;Tissues;Toxic effect;Trans-Activators;Transcription Coactivator;transcription factor;Transcriptional Regulation;Withdrawal;Work

PROJECT_TITLE: ETS1-dependent combinatorial control of oncogenic transcription in Notch-activated T-ALL

STUDY_SECTION: GRIC

STUDY_SECTION_NAME: Gene Regulation in Cancer Study Section[GRIC]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Fentanyl Misuse and Addiction;Genetics;Human Genome;Lung;Neurosciences;Opioid Misuse and Addiction;Opioids;Physical Injury - Accidents and Adverse Effects;Substance Misuse

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PROJECT NARRATIVE The weaponization of Ultrapotent synthetic opioids (UPS) has made finding a novel reversal agent a priority. The current opioid response agent, Naloxone, is not as effective against UPS opioids and does not reverse one of it’s know effects, wooden chest syndrome. Using an advanced mouse population, with genetic diversity comparable to a human population, we will identify novel targets for the development of UPS opioid reversal agents.

PI_NAMEs: BUBIER, JASON A (contact)

PROGRAM_OFFICER_NAME: VEMURI, KIRAN R V

PROJECT_TERMS: Acute;addiction;Address;aerosolized;Affect;African American population;analog;Apnea;Automobile Driving;behavioral phenotyping;Biological;Blood;Blood gas;Brain Stem;Candidate Disease Gene;Carbon Dioxide;Cardiovascular system;carfentanil;Cations;Cause of Death;cell type;Cells;Central Nervous System;Cessation of life;Chest wall structure;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Coupled;Data;detection platform;Development;differential expression;Dose;electric impedance;Epidemic;Exhibits;Fentanyl;Foundations;Gene Expression Profile;Genes;Genetic;Genetic study;Genetic Variation;genome wide association study;Genotype;Goals;hemodynamics;Human;Inbred Strains Mice;Individual Differences;individual variation;innovation;insight;Knock-out;Lethal Dose 50;Lung;Measures;Molecular;molecular phenotype;Monitor;Morphine;Moscow;Mouse Strains;Mus;Naloxone;neural;novel;Opioid;Opioid Analgesics;Opioid Antagonist;opioid overdose;Opioid Receptor;Overdose;overdose death;overdose risk;Oxygen;Pathway interactions;Patients;Peripheral Nervous System;Phenotype;Physiological;Plethysmography;Population;preBotzinger complex;prescription opioid;psychologic;Recovery;respiratory;Respiratory Mechanics;response;segregation;sex;Signal Transduction;single nucleus RNA-sequencing;Street Drugs;synthetic opioid;targeted treatment;Testing;Therapeutic;therapeutic development;Tidal Volume;Time;Tissue-Specific Gene Expression;Toxic effect;Toxicokinetics;translational impact;Variant;ventilation;Ventilatory Depression;weapons;Withdrawal;Wooden Chest Syndrome;Work

PROJECT_TITLE: Genetic Variation of Ultra-Potent Synthetic Opioid Sensitivity in Mice


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: HIV/AIDS remains an important health concern, despite significant progress in managing this chronic disease. Here we investigate one element of the viral life cycle, the translocation of the capsid across the nuclear envelope and into the nucleus of human cells, which is mechanistically poorly understood. The work in this project is designed to be translational in the long term and provide a basis to identify new molecular targets that might lead to specific treatments for patients in the future.

PI_NAMEs: SCHWARTZ, THOMAS  (contact)

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: Address;Anti-viral Therapy;Applications Grants;Avidity;Binding;Binding Sites;Biochemical;Biochemistry;Biological Assay;Biophysics;Buffers;Capsid;Capsid Proteins;Cell Nucleus;Cells;Characteristics;Chronic Disease;Collaborations;Complex;Cryo-electron tomography;Data;design;Diameter;Disease;driving force;Elements;Environment;Epidemic;Eukaryotic Cell;Foundations;Future;Glycine;Goals;Hand;Health;HIV;HIV-1;HIV/AIDS;Human;Hydrogels;In Vitro;in vivo;Individual;individualized medicine;Infection;interest;Kinetics;Knowledge;Life Cycle Stages;Liquid substance;Molecular;Molecular Target;mutant;novel;Nuclear;Nuclear Envelope;Nuclear Pore;Nuclear Pore Complex;Nuclear Pore Complex Proteins;nucleocytoplasmic transport;particle;Peptides;Phenylalanine;Physical condensation;Play;Positioning Attribute;Process;programs;Property;Proteins;Publications;receptor;Research;Reverse Transcription;Role;Series;Shapes;Side;Site;structural biology;System;Testing;Therapeutic;Thermodynamics;Translating;Viral;Virus;Work

PROJECT_TITLE: Mechanism of nuclear pore passage of the HIV-1 capsid

STUDY_SECTION: HVCD

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