ORG_CITY: BALTIMORE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PUBLIC HEALTH RELEVANCE Nearly 6 million Americans are living with Alzheimer’s Disease and Related Dementias (ADRD). The Hopkins’ Economics of Alzheimer’s Disease & Services (HEADS) Center draws on unique strengths at Johns Hopkins University (Hopkins) to advance population-based science relating to ADRD care and its consequences. The Center builds the field of ADRD-related economics and health services research and its impact through training emerging and established investigators, developing research infrastructure, and forging linkages with policy and practice communities to disseminate new knowledge.

PI_NAMEs: POLSKY, DANIEL E (contact);WOLFF, JENNIFER L.

PROGRAM_OFFICER_NAME: KIM, THERESA YOUNGJOO

PROJECT_TERMS: Address;Adult Children;advocacy organizations;Affect;Alzheimer's Disease;Alzheimer's disease related dementia;American;Area;Basic Science;care systems;career;Caregivers;caregiving;Caring;Clinical Research;collaborative environment;community building;Community Practice;Contracts;cost;Data;data enclave;Data Set;Data Sources;dementia care;Dementia caregivers;Diagnosis;Disabling;Disease;Disparity;Economics;end of life;Environment;Equity;ethnic minority;experience;Family;Family Caregiver;forging;Funding;Goals;Health;Health Promotion;Health Services Research;home based service;human very old age (85+);Infrastructure;innovation;Institution;Interdisciplinary Study;Intervention;Investigation;Knowledge;Mentorship;Methods;Mission;Monitor;novel;Personal Satisfaction;Persons;Pilot Projects;Policies;population based;Program Development;public health relevance;Quality of Care;racial minority;Request for Applications;Research;Research Infrastructure;Research Personnel;Research Support;Resource-limited setting;Resources;Role;Safety;Schools;Science;Scientist;Secure;Security;service delivery;Services;Spouses;Strategic vision;Subgroup;System;Teacher Professional Development;tool;Training;Translating;Universities

PROJECT_TITLE: Hopkins Economics of Alzheimer's Disease and Services (HEADS) Center


ADMINISTERING_IC: AG

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

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);Brain Disorders;Clinical Research;Dementia;Health Services;Neurodegenerative;Neurosciences

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_STATE: MD

PI_NAMEs: POLSKY, DANIEL E (contact)

PROJECT_TERMS: Address;Affect;Alzheimer's Disease;Alzheimer's disease related dementia;Area;Attention;Caregivers;caregiving;Caring;Collaborations;Communication;Community Practice;Community Services;Development;Disparity;Doctor of Philosophy;Economics;Ensure;Environment;Equity;Evaluation;Faculty;Family;flexibility;forging;Funding;Goals;Health Services Research;high risk;Individual;innovation;Institution;interdisciplinary collaboration;Knowledge;Leadership;meetings;member;Methodology;Monitor;Persons;Pilot Projects;Policies;Positioning Attribute;Process;Productivity;programs;Quality of Care;Reporting;Research;Research Infrastructure;Research Personnel;Resources;Schools;Science;service delivery;Services;Societies;Strategic Planning;synergism;Universities;Vision;Work

PROJECT_TITLE: Administrative (Admin) Core


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

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

ORG_CITY: DALLAS

ORG_DEPT: SURGERY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative Heterotopic ossification (HO) is the pathologic formation of extra-skeletal bone that forms almost exclusively at sites of mechanical stress. We purport that discoidin domain receptor 2 (DDR2) and injury site immobilization modify extra-cellular matrix alignment and thus changes cell fate through downstream mechanotransductive signaling. Determination of the underlying mechanisms responsible for HO will enable us to validate clinically relevant mobilization protocols and mechanotransductive therapies to combat this currently untreatable disease.

PI_NAMEs: LEVI, BENJAMIN  (contact)

PROGRAM_OFFICER_NAME: CHEN, FAYE H

PROJECT_TERMS: Anisotropy;Architecture;Automobile Driving;bone;Burn injury;cell fate specification;Cell Lineage;Cells;Chemicals;Clinical;clinical translation;clinically relevant;Collagen;Collagen Receptors;Collagen Type I;combat;Communication;Cre lox recombination system;Data;Data Set;Devices;discoidin domain receptor 2;discoidin receptor;Disease;Elements;Exposure to;Extracellular Matrix;fibula;Focal Adhesion Kinase 1;Gene Expression Profile;Genetic;Genetic Transcription;Heterotopic Ossification;hip replacement arthroplasty;Human;Immobilization;In Vitro;in vivo;in vivo Model;inducible Cre;inhibitor therapy;Injury;insight;Intervention;joint mobilization;Joints;Label;Lesion;Ligands;Limb structure;Link;lipid biosynthesis;Mechanical Stress;mechanotransduction;Mesenchymal Stem Cells;Modeling;Molecular;mouse model;Mus;musculoskeletal injury;novel;osteochondral tissue;Osteogenesis;Pathologic;Pathway interactions;Patients;Periodicity;Phase;Physical therapy;Physiologic Ossification;prevent;Process;progenitor;programs;Protein Tyrosine Kinase;Protocols documentation;PTK2 gene;Radial;Regulation;Role;Series;Signal Transduction;single-cell RNA sequencing;Site;stem cell fate;Stretching;System;targeted treatment;Therapeutic;Therapeutic Intervention;tibia;Traumatic injury;ulna;Work

PROJECT_TITLE: Impacts of mechanosensation and matrix architecture on cell fate specification in traumatic heterotopic ossification

STUDY_SECTION: SBDD

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


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;Health Services;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

PI_NAMEs: BOYD, CYNTHIA MELINDA (contact)

PROJECT_TERMS: Address;Affect;Alzheimer's Disease;Alzheimer's disease related dementia;Area;Budgets;career;Caregivers;caregiving;Caring;clinical care;Communities;community center;Community Practice;Data;data enclave;Data Security;Development;Disparity;Economics;Electronic Health Record;Enrollment;Ensure;Environment;Equity;Faculty;Family;Fee-for-Service Plans;forging;Funding;Future;Goals;Health Services Research;help-seeking behavior;innovation;Knowledge;Leadership;Managed Care;Medicare;Mentorship;Methods;Natural Language Processing;novel;older adult;Pattern;Persons;Pilot Projects;Policies;population based;Prevalence;Process;Program Development;programs;racial disparity;Research;Research Infrastructure;Research Personnel;Research Project Grants;Resources;senior faculty;Services;Structure;Teacher Professional Development;Testing;text searching;theories;Translating;United States National Institutes of Health;Work

PROJECT_TITLE: Program Development (Pilot) Core


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Asthma;Genetics;Lung

ORG_CITY: NEW YORK

ORG_DEPT: PHARMACOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE Lineage-specific cell differentiation is controlled by gene transcription in chromatin that is fundamental to human biology and diseases. While key transcriptional and chromatin regulators have been identified, it remains elusive as to how they work in concert to direct ordered gene expression in chromatin in response to physiological and environmental cues. In this study, we will investigate the fundamental transcriptional mechanisms required for specification of disease-causing cell types, and establish a new therapeutic strategy for future development of more effective and safer treatment of allergic inflammation such as asthma.

PI_NAMEs: CHEUNG, KALUNG ;ZHOU, MING-MING  (contact)

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: Acetylation;adaptive immunity;Affect;allergic airway inflammation;Allergic Disease;Allergic inflammation;Asthma;asthma model;Atopic Dermatitis;base;Binding;Bromodomain;CD4 Positive T Lymphocytes;Cell Differentiation process;Cell Lineage;cell type;Cells;Chemicals;Chromatin;Complex;Crohn's disease;Cues;cytokine;derepression;design;Development;Disease;Down-Regulation;effective therapy;Ensure;FOXP3 gene;Future;GATA3 gene;Gene Activation;Gene Expression;Gene Order;gene repression;genetic approach;Genetic Transcription;Genomics;histone acetyltransferase;Histone H3;Human Biology;human disease;Immunomodulators;immunoregulation;in vivo;Inflammatory;inhibitor;insight;Interleukin-4;Ligands;Ligase;Lysine;Mediating;member;Methods;Methylation;Molecular;mouse model;Mus;neutralizing antibody;next generation;novel;novel therapeutic intervention;Ovalbumin;Pathogenicity;Physiological;Polycomb;programs;protein degradation;Protein Family;Proteins;Pyroglyphidae;Regulation;Regulatory T-Lymphocyte;Repression;response;Role;Specific qualifier value;Therapeutic;Thymus Gland;Time;transcription factor;Transcriptional Activation;Transcriptional Regulation;transcriptomics;transdifferentiation;Treatment Efficacy;Treatment-related toxicity;Ubiquitination;Work;YY1 Transcription Factor

PROJECT_TITLE: Mechanism of Transcriptional Regulation of Th2 Cell Development

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


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;Caregiving Research;Clinical Research;Dementia;Health Services;Neurodegenerative;Neurosciences

PI_NAMEs: WOLFF, JENNIFER L. (contact)

PROJECT_TERMS: Academia;Address;Advocacy;Affect;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Area;Awareness;Behavioral Sciences;care delivery;career;caregiving;Caring;clinical practice;Communication;Communities;Community Practice;Community Services;Decision Making;Disparity;Economics;Educational workshop;Equity;Family;forging;Goals;Government;Health;health care delivery;health economics;health management;Health Policy;Health Services;Health Services Research;improved;Infrastructure;innovation;Institution;interest;Knowledge;Leadership;member;mid-career faculty;Online Systems;outreach;Peer Review;Persons;Policies;Policy Maker;Positioning Attribute;Printing;professor;Psychiatry;Publications;Research;research data dissemination;Research Infrastructure;Research Methodology;Research Personnel;Resources;service delivery;Services;skills;social media;Structure;Teaching Method;Techniques;Training;Translating;Translations;trend;webinar

PROJECT_TITLE: External Research Resources Support and Dissemination (R&D) Core


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Data Science;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

PROJECT_TERMS: Address;Affect;Aging;Agreement;Alzheimer's Disease;Alzheimer's disease related dementia;Area;care providers;Caregivers;caregiving;Caring;Community Practice;Computer software;Computerized Medical Record;Creativeness;Data;data access;Data Collection;data enclave;data infrastructure;data privacy;Data Protection;data reuse;Data Security;Data Set;Data Sources;data warehouse;Dementia;design;Development;Diagnosis;Disparity;Economics;Ensure;Environment;Equipment and supply inventories;Equity;evidence base;Family;forging;Foundations;Genetic;Geography;Health;Health Services Research;Healthcare;Home Care Services;Hospitals;Individual;innovation;insight;Investments;Knowledge;Licensing;Link;Maintenance;Marketing;Medicare/Medicaid;Outcome;Patients;payment;Persons;Pilot Projects;Policies;population survey;Privacy;privacy protection;Probability;Process;programs;Protocols documentation;Provider;Research;Research Infrastructure;Research Personnel;Resources;Secure;Security;service delivery;Services;Skilled Nursing Facilities;social media;Social support;System;Talents;Training;treatment and outcome;treatment disparity;trend;Update;Variant

PROJECT_TITLE: Remote Data Enclave Core (RDEC)


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;Biotechnology;Brain Disorders;Dementia;Genetics;Machine Learning and Artificial Intelligence;Neurodegenerative;Neurosciences;Physical Activity;Prevention

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: PROJECT NARRATIVE Physical activity has extensive and well-documented neuroprotective effects, benefitting cognitive function during healthy aging and reducing the risk of Alzheimer Disease (AD). However, the mechanisms responsible for these benefits remain largely unknown, making identification of the circulating signals that underlie the CNS-targeting benefits of exercise a major advance for developing CNS rejuvenating therapeutics against AD. The following studies address muscle proteostasis, a pathway highly activated during exercise, as a potential new regulator of the neurocognitive benefits of exercise, as well as new therapeutic intervention for preservation of CNS function in AD.

PI_NAMEs: CORTES, CONSTANZA JAVIERA (contact)

PROGRAM_OFFICER_NAME: PETANCESKA, SUZANA

PROJECT_TERMS: Address;Affect;age related;aged;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease risk;Automobile Driving;Autophagocytosis;Behavior Therapy;Bioinformatics;Brain;cell type;Cells;Central Nervous System;Circulation;clinical investigation;Cognition;cognitive benefits;cognitive function;Communication;Complement;Computer Models;Data;Data Science;Data Set;differential expression;Disease;disease prognosis;drug repurposing;Drug usage;Event;Exercise;FDA approved;Gene Expression Profile;gene therapy;Genetic Transcription;geroprotector;healthy aging;Hippocampus;Human;human data;improved;innovation;Intervention;Machine Learning;Maps;Memory;Metabolic;Metabolism;mimetics;Modeling;Molecular;Molecular Profiling;Molecular Target;mouse model;Mus;Muscle;Nerve Degeneration;Nervous System Physiology;Neurocognitive;Neurodegenerative Disorders;Neurofibrillary Tangles;neurogenesis;neuroinflammation;neuroprotection;neurotrophic factor;novel;novel therapeutic intervention;overexpression;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;Phenotype;Physical activity;Physical Exercise;Physiological;Plasma;Population;Positioning Attribute;pre-clinical;preservation;programs;Proteins;Proteomics;proteostasis;proteotoxicity;Rejuvenation;response;Risk;Risk Reduction;Running;Senile Plaques;Signal Transduction;Skeletal Muscle;Stimulus;Synaptic plasticity;systemic inflammatory response;tau Proteins;Testing;Therapeutic;therapeutic development;Therapeutic Intervention;Tissues;tool;transcription factor;transcriptome;transcriptome sequencing;transcriptomics;Transducers;transfer learning;Transgenic Mice;Transgenic Organisms;Translations

PROJECT_TITLE: Exercise-Associated Signaling Against CNS Aging and Alzheimer's Disease


ED_INST_TYPE: UNIVERSITY-WIDE

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;Prevention

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Narrative Early onset Alzheimer's Disease and Related Dementias (EOD) is a devastating but under-studied condition. We propose here to pool and rigorously harmonize data to create a cohort with a sizable number of EOD events to estimate EOD incidence in the general population, identify predisposing and/or protective physiologic and behavioral risk factors, and study whether a favorable midlife risk profile in the presence of genetic predisposition delays the occurrence of EOD. Findings will provide actionable insights regarding targets for delaying the onset of EOD.

PI_NAMEs: SEDAGHAT, SANAZ  (contact)

PROGRAM_OFFICER_NAME: ANDERSON, DALLAS

PROJECT_TERMS: Adult;Affect;Age;Age of Onset;Age Years;Alcohol consumption;Alzheimer's Disease;Alzheimer's disease related dementia;Behavioral;biobank;Blood Pressure;Blood Vessels;Body mass index;burden of illness;cardiovascular health;cardiovascular risk factor;Cardiovascular system;Characteristics;Clinical;Cognitive;cohort;Cohort Studies;Craniocerebral Trauma;Data;data harmonization;dementia risk;demographics;Development;Diabetes Mellitus;Diagnosis;Disease;Disease Progression;Distress;Early Diagnosis;early onset;Early Onset Alzheimer Disease;Education;Eligibility Determination;Epidemiology;Evaluation;Event;Frontotemporal Dementia;General Population;Genes;Genetic;Genetic Predisposition to Disease;Genetic Risk;genetic variant;Health behavior;Heart Diseases;High Prevalence;high risk;human old age (65+);Hypertension;Incidence;Individual;Infrastructure;insight;International;Intervention;Late Onset Alzheimer Disease;Lewy Body Dementia;Life Style;lifestyle factors;Light;Lipids;Measures;Medical;Mental Depression;middle age;multi-ethnic;Nature;non-genetic;Participant;Patients;Persons;Physical activity;Physiological;polygenic risk score;Population;population based;Population Study;Predisposing Factor;Predisposition;presenilin-1;presenilin-2;Prevalence;Prevention;Prevention strategy;Primary Prevention;Prospective Studies;protective factors;Quality of life;Race;rare variant;Renal function;Reporting;Risk;Risk Factors;Role;Sample Size;screening;Secondary Prevention;sex;Smoking;Social isolation;Stroke;stroke incidence;Symptoms;Syndrome;tertiary prevention;Testing;Time;trend;Variant;Vascular Dementia;Vulnerable Populations;Woman;young adult

PROJECT_TITLE: Early Onset Alzheimer's Disease and Related Dementias: A Population-Based Approach to Identify Characteristics and Risk Factors

STUDY_SECTION: AIMR

STUDY_SECTION_NAME:
Aging, Injury, Musculoskeletal, and Rheumatologic Disorders Study
Section[AIMR]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Colorectal Cancer;Digestive Diseases;Immunotherapy;Liver Disease;Radiation Oncology

ORG_CITY: BUFFALO

ORG_NAME: ROSWELL PARK CANCER INSTITUTE CORP

PHR: PROJECT NARRATIVE Liver metastasis are a common cause of cancer-related deaths and are associated with a poor response to immune checkpoint blockade (ICB) immunotherapy. Although liver-directed radiation improves the ability of ICB to control liver metastasis, response rates are often short-lived. Novel immunotherapeutic approaches that can stimulate antitumor immunity in the liver have the potential to boost liver-directed radiation plus ICB mediated control of liver metastasis. Towards this end, our research will advance our liver trophic immunotherapy drug called entolimod as a way to improve liver-directed radiotherapy and ICB response rates. The fact that entolimod, liver-directed radiotherapy, and ICB are in the cancer clinic ensures the feasibility of combining these therapies into a single novel and effective therapy to improve the dire survival outcomes in patients with liver metastasis.

PI_NAMEs: BRACKETT, CRAIG M. (contact)

PROGRAM_OFFICER_NAME: BUCHSBAUM, JEFFREY

PROJECT_TERMS: Abscopal effect;Address;Aftercare;Agonist;anti-CTLA4;anti-PD-1;Antibodies;Cancer Etiology;Cancer Patient;CD8-Positive T-Lymphocytes;Cell Death;Cell surface;Cessation of life;Clinic;Clinical;Clinical Data;Colon;colon cancer metastasis;Colorectal Cancer;Combined Modality Therapy;CT26;cytokine;Cytoplasm;Disease;effective therapy;Ensure;FDA approved;Flagellin;Gene Expression Profile;Genetic;genetic signature;Goals;healthy volunteer;Hepatocyte;Human;Immune;immune checkpoint blockade;immunomodulatory therapies;immunoregulation;Immunotherapeutic agent;Immunotherapy;improved;Inflammasome;Injections;innovation;Innovative Therapy;Interferon Type II;Interferons;Irradiated tumor;Letters;Link;Liver;Malignant Neoplasms;Measures;Mediating;Melanoma;Metastatic Neoplasm to the Liver;Modeling;Mus;neoantigens;Neoplasm Metastasis;neutrophil;nonhuman primate;Normal tissue morphology;novel;novel therapeutics;Operative Surgical Procedures;Outcome;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Phase;pre-clinical;Pre-Clinical Model;pre-clinical therapy;Publishing;Radiation;Radiation therapy;Radiation Toxicity;Radioimmunotherapy;Research;response;Rodent;Safety;Salmonella;Sampling;Shapes;Signal Transduction;Site;Source;survival outcome;T cell response;Testing;therapy outcome;Time;TLR5 gene;Translating;Treatment Efficacy;treatment response;tumor;Tumor Immunity;tumor-immune system interactions;Work

PROJECT_TITLE: TLR5 enhancement of liver-directed radiotherapy plus immune checkpoint blockade against irradiated liver metastasis and abscopal tumors

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TIR-W(01)Q]


ADMINISTERING_IC: GM

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: ATLANTA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: NARRATIVE The ability of bacteria to actively export antibiotics out of their cells through efflux pumps is a prominent mechanism contributing to the escalating global antibiotic resistance health crisis. My research will investigate how specific efflux systems belonging to a family of pumps found in many pathogenic bacteria accomplish the essential processes of antibiotic uptake and recognition for export out of the cell. In addition to providing me the interdisciplinary training necessary to become an independent researcher, my results will enhance our understanding of efflux pump activity/ function and could support development of new pump inhibitors or guide redesign of current therapeutics to reduce their export while retaining antibiotic efficacy.

PI_NAMEs: KAVANAUGH, LOGAN GLENN (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: Adaptor Signaling Protein;Affinity;Aminoglycoside resistance;Aminoglycosides;antibiotic efflux;Antibiotic Resistance;Antibiotics;Bacteria;beta-Lactams;Binding;Biological Assay;Calorimetry;cancer care;career;Carrier Proteins;Cells;Centers for Disease Control and Prevention (U.S.);Charge;Childbirth;Clinical;combat;Complement;Complex;Computer Models;Coupled;Cryoelectron Microscopy;Dangerousness;design;Development;Discrimination;Distal;Drug Efflux;efflux pump;Escherichia coli;Family;Health;in silico;In Vitro;in vivo;Infection;inhibitor;insight;Knock-out;Lactams;Lead;Membrane;Membrane Proteins;Membrane Transport Proteins;Minimum Inhibitory Concentration measurement;Modeling;Molecular;Mutagenesis;mutant;novel;novel strategies;Operative Surgical Procedures;pathogen;pathogenic bacteria;Pathway interactions;periplasm;Pharmaceutical Preparations;Pneumonia;preference;Procedures;Process;Property;protein folding;Proteins;Pseudomonas aeruginosa;Public Health;Publishing;Pump;Reporting;Research;Research Personnel;Resistance;resistance mechanism;Resolution;Sepsis;Shapes;Site-Directed Mutagenesis;skills;Structure;Substrate Specificity;System;Testing;Therapeutic;Titrations;Training;uptake;Variant;Vestibule;X-Ray Crystallography

PROJECT_TITLE: Molecular basis for substrate discrimination by transporter protein MexY of the MexXY-OprM efflux pump in Pseudomonas aeruginosa


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;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Discovery of Drugs that Modulate Neuroinflammation for the Treatment of Alzheimer's Disease Narrative We identified a drug that reduces inflammation and increases the synthesis of a protective neurosteroid in the brains of animal models of neurodegeneration, and believe an improved analog may have utility to treat Alzheimer’s Disease. We propose to further optimize the molecule’s structure and improve its activity and pharmacokinetics. Finally, we will test the best compounds in mouse models of Alzheimer’s Disease and identify a lead for further clinical development. 1

PI_NAMEs: HODGETTS, KEVIN  (contact)

PROGRAM_OFFICER_NAME: REFOLO, LORENZO

PROJECT_TERMS: Affinity;Aggressive behavior;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;analog;Animal Model;Anti-Anxiety Agents;Antiinflammatory Effect;Anxiety;APP-PS1;aqueous;Binding;Biological Assay;Brain;Clinical;clinical development;Cognitive deficits;cytokine;Data;Dementia;design;Development;disease model;Disease Progression;Dose;Drug Kinetics;Drug Modulation;efficacy evaluation;Elderly;enantiomer;FDA approved;Goals;Human;Impaired cognition;improved;In Vitro;in vivo;Industry Standard;Inflammation;Inflammatory;Lead;Learning;Link;Measures;Memory;mouse model;Mus;Nerve Degeneration;Neurodegenerative Disorders;Neuroglia;neuroinflammation;neuropathology;neurosteroids;novel;Pathogenesis;Pathology;Persons;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;pre-IND studies;Pregnenolone;Property;receptor;Research;Risk;Rodent;Safety;scale up;sedative;Senile Plaques;small molecule;Solubility;Structure;Symptoms;Synapses;tau Proteins;Testing;TNF gene;Toxic effect;Work

PROJECT_TITLE: Discovery of Drugs that Modulate Neuroinflammation for the treatment of Alzheimer's Disease


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: Chicago

ORG_NAME: NORTHWESTERN UNIVERSITY

ORG_STATE: IL

PHR: NARRATIVE The proposed institutional training program will support evidence-based cross-disciplinary education and training of a diverse cohort of chemistry and biology graduate students with the goal of providing them with the tools and perspectives needed to address the complex problems that are at the center of 21st century biomedical research.

PI_NAMEs: KELLEHER, NEIL L (contact)

PROGRAM_OFFICER_NAME: HARTON, MARIE DEBORAHGAYNELLE

PROJECT_TITLE: Chemistry of Life Processes Predoctoral Training Program

STUDY_SECTION: TWD

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


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: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Lipidomic studies have identified multiple dysregulated lipid metabolic pathways in aging brain and neruodegeneration, however, synthesis of these data sets, which are often incomplete, has not yet yielded a clear understanding of mechanisms of lipid dyshomeostasis in aging. Imaging Mass Spectrometry is an emerging technology that has not yet been applied exhaustively to aging and mouse models of neurodegeneration and has potential to furnish valuable spatial information in mouse brain. We will test the hypothesis that genetic manipulation of dysregulated lipid metabolic pathways in the brain can rescue cognitive, functional and pathological deficits associated with Alzheimer's disease.

PI_NAMEs: MCINTIRE, LAURA BETH JOHNSON (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: abeta accumulation;Acyl Coenzyme A;Age;age related;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease risk;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Animal Model;Animals;Apolipoprotein E;apolipoprotein E-4;Atlases;ATP binding cassette transporter 1;Autopsy;Behavioral;Biological Markers;Biology;biomarker discovery;Brain;brain cell;Brain region;brain tissue;cell type;Cerebrospinal Fluid;cholesterol transporters;Coenzyme A Ligases;Cognitive;Cognitive deficits;cognitive function;Data;Data Set;Disease;Docosahexaenoic Acids;Electrophysiology (science);Electrospray Ionization;Emerging Technologies;Enzymes;Etiology;Explosion;familial Alzheimer disease;Genes;Genetic;genetic manipulation;genetic risk factor;Genetic study;genetic variant;genome wide association study;Genotype;Head;high risk;Hippocampus;Homeostasis;Human;human data;human disease;Human Genetics;Inositol;Investigation;Knock-in;Knock-out;Knowledge;Late Onset Alzheimer Disease;Learning;lipid metabolism;lipid transport;lipidome;lipidomics;Lipids;liquid chromatography mass spectrometry;Liquid substance;Long-Term Potentiation;Maps;mass spectrometric imaging;Mass Spectrum Analysis;Mediator;Memory;Metabolic;Metabolic Pathway;metabolomics;Methods;Mouse Embryonic Stem Cells;mouse genetics;mouse model;Mus;Nature;Nerve Degeneration;Neurodegenerative Disorders;overexpression;Pathologic;Pathology;Pathway interactions;Performance;Phase;Phenocopy;Phosphatidylinositols;Phospholipase A2;phospholipase D2;Phospholipids;Phosphoric Monoester Hydrolases;Physiological;Plasma;Polyphosphates;Polyunsaturated Fatty Acids;Predisposition;Proliferating;Reporting;Resistance;Rodent;spatial memory;Support System;Synapses;SYNJ1 gene;synthetic enzyme;System;Testing;Tg2576;Therapeutic;therapeutic target;Transgenes;Variant;water maze;Wild Type Mouse;Work

PROJECT_TITLE: Acyl chain remodeling and regional lipid dysregulation in Alzheimer's disease


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);Biotechnology;Brain Disorders;Clinical Research;Dementia;Neurodegenerative;Neurosciences

ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE Alzheimer’s disease affects millions of people in the United States and worldwide, yet no effective treatments exist for this devastating neurodegenerative disease of aging. This research project aims to better understand the protein changes that occur in the brain during Alzheimer’s disease so that we can develop therapies to treat the disease. It also aims to use this improved understanding to develop better diagnostic tests for Alzheimer’s disease.

PI_NAMEs: JOHNSON, ERIK C.B. (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: AD transgenic mice;Affect;Age;age related neurodegeneration;aging related disease;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease test;Alzheimer's disease therapy;Alzheimer’s disease biomarker;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Animal Disease Models;Animal Model;Area;Astrocytes;autosomal dominant Alzheimer's disease;autosomal dominant mutation;autosome;Biochemistry;Bioinformatics;Biological;Biological Markers;Biology;biomarker discovery;Brain;Brain Diseases;Brain region;brain tissue;career development;case control;Central Nervous System;Cerebrospinal Fluid;Clinical;Comparative Study;data acquisition;Data Analyses;design;Diagnosis;Diagnostic tests;differential expression;Disease;disorder subtype;Doctor of Medicine;Doctor of Philosophy;early onset;Early Onset Alzheimer Disease;effective therapy;experimental study;frontal lobe;Future;Genetic;Goals;Hippocampus;Homeostasis;Human;human disease;improved;insight;Knowledge;Label;Late Onset Alzheimer Disease;Life Expectancy;Liquid substance;Mass Spectrum Analysis;Measures;medical specialties;Mentors;Metabolism;Modeling;Molecular;Molecular Biology;molecular marker;mouse model;Mouse Protein;multidisciplinary;Mus;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Neurology;neuropathology;novel strategies;Outcome;Pathologic;Pathway Analysis;Persons;Physicians;Population;preclinical study;Prefrontal Cortex;presenilin;preservation;Process;Prognosis;programs;protein aggregation;protein biomarkers;protein expression;Proteins;Proteome;Proteomics;Public Health;Research;Research Project Grants;Research Proposals;Research Technics;Scientist;Systems Biology;tau dysfunction;tau Proteins;Techniques;Testing;therapeutic target;therapy development;Training;translational potential;translational study;United States

PROJECT_TITLE: Brain Proteomic Network Analysis to Elucidate Mechanisms and Biomarkers for Alzheimer's Disease

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Basic Neuroscience of Aging Study Section[NIA-N]


NIH_SPENDING_CATS: Aging;Clinical Research;Patient Safety

ORG_CITY: Oakland

ORG_NAME: KAISER FOUNDATION RESEARCH INSTITUTE

PHR: NARRATIVE Patient frailty increases the risk for surgical complications, which are common, costly, and deadly, especially for older Americans. To improve surgical care for older adults, we will investigate whether electronic measures of frailty can help reduce complications by identifying which patients are likely to be readmitted to the hospital or die soon after surgery.

PI_NAMEs: FELICIANO, ELIZABETH MARJORIE CESPEDES (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Abdomen;Acute;Address;adverse outcome;Age;Aging;Algorithms;American;biological age;Caring;Chronic Disease;Chronology;Clinical;clinical care;Code;Complex;computer science;Computer software;Consumption;cost;Counseling;Data;Data Set;Decision Making;Diagnostic;digital data;electronic data;Electronic Health Record;Electronics;Exhibits;frailty;functional status;Future;Goals;high risk;Hospital Costs;Hospital Mortality;hospital readmission;Hospitals;improved;Infiltration;Informatics;innovation;inpatient surgery;Intervention;Laboratories;Length of Stay;Manuals;Measures;Methodology;Modeling;Morbidity - disease rate;mortality;Muscle;muscle form;Muscular Atrophy;National Institute on Aging;older adult;older patient;Operative Surgical Procedures;Pathway interactions;patient response;Patient-Focused Outcomes;Patients;Performance;performance tests;Perioperative;Perioperative Care;Physical Function;Physiological;Population;Population Heterogeneity;Postoperative Period;postoperative recovery;predictive modeling;Predictive Value;Process;profiles in patients;programs;prospective;Research;Risk;Risk Factors;risk stratification;sarcopenia;Scanning;secondary analysis;Severity of illness;shared decision making;Skeletal Muscle;Standardization;stressor;surgery outcome;Surgical complication;surgical risk;Technology;Time;tool;Validation;X-Ray Computed Tomography

PROJECT_TITLE: Informatics approaches to assessing patient frailty in surgical care

STUDY_SECTION: BCHI

STUDY_SECTION_NAME: Biomedical Computing and Health Informatics Study Section[BCHI]


ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Project Narrative Mitochondrial Ca2+ uptake plays an essential role in regulating ATP production, buffering cytosolic Ca2+, maintaining redox homeostasis and triggering cell death; dysregulation of these Ca2+ uptake mechanisms has been implicated in several neuromuscular, cardiac and metabolic diseases. The proposed work utilizes application of direct electrophysiological methods on the native mitochondrial membranes to study the gating of mitochondrial Ca2+ uniporter (MCU), the principal pathway for mitochondrial Ca2+ entry. This work will potentially identify novel molecular mechanisms that can be therapeutically targeted to modulate MCU activity in disease states.

PI_NAMEs: GARG, VIVEK  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Binding;Biochemical;Bioenergetics;Biological Assay;biophysical properties;Buffers;calcium uniporter;Cell Death;Cell Line;Cells;Complex;CRISPR/Cas technology;Cysteine;Cytoplasm;Data;density;Development;direct application;Disease;Dominant-Negative Mutation;drug development;EF-Hand Domain;Electrophysiology (science);Enzymes;Exercise;Fibroblasts;Functional disorder;Goals;Heart Diseases;Heart failure;Homeostasis;human disease;Immune System Diseases;Individual;Inner mitochondrial membrane;innovation;insight;Intervention;Kinetics;Knock-out;knockout gene;Knockout Mice;Learning;Location;loss of function mutation;Luminal region;Macromolecular Complexes;Malignant Neoplasms;Measures;Mediating;Membrane;Metabolic Diseases;Methodology;Methods;Mitochondria;mitochondrial dysfunction;Mitochondrial Matrix;mitochondrial membrane;mitochondrial permeability transition pore;Molecular;Molecular Structure;Movement Disorders;Mus;Muscular Dystrophies;Mutagenesis;mutant;Mutation;Myopathy;Nerve Degeneration;Nervous System Disorder;Neuromuscular Diseases;novel;overexpression;Oxidation-Reduction;paralogous gene;patch clamp;Patch-Clamp Techniques;Pathologic;Pathway interactions;Permeability;pharmacologic;physiologic model;Physiological;Physiology;Play;prevent;Probability;Production;Proteins;Publishing;Regulation;Reperfusion Injury;Resolution;response;Rest;Role;Side;Skeletal Muscle;stoichiometry;Stroke;Structure;success;System;targeted treatment;Techniques;Testing;Therapeutic;therapeutic target;Tissues;uptake;Work

PROJECT_TITLE: Molecular Physiology of Mitochondrial Calcium Uniporter

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


NIH_SPENDING_CATS: Aging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Neurodegenerative;Neurosciences;Osteoporosis;Parkinson's Disease;Physical Injury - Accidents and Adverse Effects;Prevention

ORG_CITY: SAN FRANCISCO

ORG_NAME: CALIFORNIA PACIFIC MED CTR RES INSTITUTE

PHR: Patients with Parkinson's disease have a high risk of falls and fractures but few receive treatment. In a nation- wide trial, we will test whether intravenous zoledronic acid given at home reduces that risk without burdensome clinic visits. If so, this home-based treatment could be widely use to reduce fractures in these patients.

PI_NAMEs: CUMMINGS, STEVEN RON (contact);TANNER, CAROLINE M.

PROGRAM_OFFICER_NAME: SAZONOVA, IRINA Y

PROJECT_TERMS: Acids;Address;Age;barrier to care;Binding;bisphosphonate;Blinded;bone;Bone Density;bone loss;Bone remodeling;Calcium;Cessation of life;Clinic Visits;Clinical;clinical diagnosis;Communities;Data;design;Diagnosis;diaries;Disabling;Documentation;economic evaluation;efficacy testing;efficacy trial;Enrollment;Evaluation;experience;fall risk;falls;follow-up;Foundations;Fracture;fracture risk;Guidelines;health economics;Health system;high risk;Hip Fractures;Home;human old age (65+);improved;Infusion procedures;Institutional Review Boards;Intravenous;Medical;men;Monitor;mortality;Movement Disorders;Neurologist;non-compliance;Nursing Research;older patient;Oral;Osteoporosis;Parkinson Disease;Patient Care;Patients;pelvis fracture;Pharmaceutical Preparations;pharmacologic;Placebo Control;Placebos;population based;preservation;prevent;Prevention;primary endpoint;randomized placebo controlled trial;randomized trial;Recovery of Function;recruit;Research Design;Risk;Risk Reduction;safety assessment;screening;secondary endpoint;Specialist;Subgroup;Surveys;Telemedicine;Testing;treatment response;Uncertainty;Visit;Vitamin D supplementation;Woman;Zoledronic Acid

PROJECT_TITLE: Prevention of Fractures in Patients with Parkinson's Disease

STUDY_SECTION_NAME: Clinical Aging Study Section[NIA-C]


ADMINISTERING_IC: DK

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Acylcarnitines are a lipid in the blood that are known to be elevated during obesity and are known to cause insulin resistance. In this proposal we describe the discovery and functional characterization of a novel transporter that shuttles acylcarnitines from the blood into cells. We will investigate the impact of the loss of this transporter on metabolic health allowing us to identify new physiological and molecular mechanisms that can be targeted for the treatment of type 2 diabetes and obesity related diseases.

PI_NAMEs: SIMCOX, JUDITH ANNE (contact)

PROGRAM_OFFICER_NAME: LYNCH, CHRISTOPHER

PROJECT_TERMS: acylcarnitine;Address;Adipocytes;Adipose tissue;Adult;Affect;American;Biological Assay;Biological Markers;Blood;blood glucose regulation;Brown Fat;Cardiovascular Diseases;Cardiovascular system;Carrier Proteins;Cell Culture Techniques;Cell membrane;Cell Physiology;Cells;Cessation of life;ChIP-seq;chromatin immunoprecipitation;CRISPR library;CRISPR screen;Development;Diabetes Mellitus;Disease;Energy Metabolism;experimental study;fatty acid oxidation;Gene Expression;Genomics;Glucose;glucose tolerance;glucose uptake;Health;Heart;Homeostasis;improved;In Vitro;in vivo;in vivo Model;Individual;insight;insulin regulation;Insulin Resistance;insulin sensitivity;insulin signaling;Knock-out;Knowledge;Link;Lipids;Liver;Luciferases;Mass Spectrum Analysis;Mediating;Membrane Transport Proteins;Metabolic;Metabolic Diseases;Metabolism;Modeling;Molecular;mouse model;Mus;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Obesity associated disease;obesity treatment;old mice;overexpression;Overweight;Pathway interactions;Pharmacological Treatment;Physiologic Thermoregulation;Physiological;Plasma;Population;PPAR gamma;prevent;Primary carcinoma of the liver cells;Process;Production;promoter;protein expression;Regulation;Reporter;resistance mechanism;Respiration;response;Signal Transduction;Skeletal Muscle;solute;Source;Supercritical Fluid Chromatography;targeted treatment;theories;therapeutic target;Thermogenesis;Time;Tissue Sample;tissue/cell culture;Tissues;Transcript;United States;uptake;Work

PROJECT_TITLE: Discovery and characterization of a novel acylcarnitine transporter in brown adipocytes

STUDY_SECTION: POMD

STUDY_SECTION_NAME: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Eye Disease and Disorders of Vision;Neurosciences;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: LOS ANGELES

ORG_NAME: CHILDREN'S HOSPITAL OF LOS ANGELES

PHR: Project Narrative The proper assembly and maintenance of neural circuits in the retina is essential to visual function and becomes deranged in the setting of inherited retinal disorders. The primary objective of this proposal is to investigate fundamental mechanisms of synapse formation, maintenance, and specificity between photoreceptors and bipolar cells in the human retina by using stem cell-derived human retinal organoids. The proposed studies will together determine the logic underlying human retinal synapse formation and identify potential therapeutic targets to preserve or regenerate synaptic connectivity in the disease state.

PI_NAMEs: NAGIEL, AARON  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Address;Age of Onset;Agonist;antagonist;Behavior;Biological Models;Calcium Channel;California;career;cell behavior;Cell Line;Cell Physiology;Cell Therapy;Cells;Characteristics;Childhood;Clustered Regularly Interspaced Short Palindromic Repeats;Cone;Dendrites;Development;Developmental Process;Disease;Engineering;Exhibits;experimental study;Exploratory Behavior;Foundations;Four-dimensional;Functional disorder;functional restoration;Funding;Genes;Germ Cells;Glutamate Receptor;glutamatergic signaling;Glutamates;Hour;Human;human disease;human embryonic stem cell;human induced pluripotent stem cells;human model;human stem cell-derived;Image;Immunofluorescence Microscopy;Impairment;in vitro Model;in vivo;induced pluripotent stem cell;Inherited;Institution;K-Series Research Career Programs;Laboratory Research;Link;live cell imaging;Logic;Los Angeles;Maintenance;Measures;Mediating;Membrane;Mentors;Methods;Modeling;Molecular;Molecular Target;Motility;Motivation;mouse model;mutant;Natural regeneration;neural circuit;Neurons;Neurophysiology - biologic function;Neurosciences;Night Blindness;Organoids;Pathologic;Pathology;Pathway interactions;Pediatric Hospitals;pharmacologic;Photoreceptors;Physicians;postsynaptic;Pregnancy;preservation;presynaptic;programs;Proteins;Publishing;Recovery of Function;Reporter;Research;Retina;Retinal Diseases;Retinal Dystrophy;retinal rods;Retinitis Pigmentosa;ribbon synapse;Rod;Role;Scientist;Site;skills;Specialist;Specificity;stem cell organoids;stem cells;Synapses;Synaptic Transmission;synaptogenesis;System;Techniques;Testing;therapeutic target;Time;Tissues;Universities;Vertebrate Photoreceptors;Vision;visual processing;Visual System;Work

PROJECT_TITLE: Development and Maintenance of the Human Photoreceptor-Bipolar Cell Synapse.


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Eye Disease and Disorders of Vision;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Rare Diseases

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Up to 10% of babies worldwide are born premature, and at risk for poor vision and neurologic impairments later in life. There remains an unmet need to understand how postnatal exposures change eye development in premature infants and whether the eye can provide a window to elucidate changes that are happening in the brain. Our study will utilize non-invasive eye imaging with optical coherence tomography and angiography in neonates requiring intensive care to: (1) help us understand how the retina and its blood supply are affected by oxygen use and retinopathy of prematurity treatment in the immediate postnatal period, and (2) inform about whether measurements taken from these postnatal non-invasive eye pictures can predict later retinopathy of prematurity, vision, and neurodevelopmental outcomes.

PI_NAMEs: CHU, ALISON ;TSUI, IRENA  (contact)

PROGRAM_OFFICER_NAME: COOK, TIFFANY

PROJECT_TERMS: 3 year old;5 year old;Adult;Affect;Age;Alzheimer's Disease;Anesthesia procedures;Angiography;arm;Biological Markers;Birth;Birth Weight;blood vessel development;Blood Vessels;Brain;Cause of Death;Child;Choroid;Cognitive;cohort;comorbidity;Counseling;critical period;Cystoid Macular Edema;Data;Development;Devices;Diabetic Retinopathy;Disease Progression;Early Intervention;Epidemic;Evaluation;Exposure to;Eye;Eye Development;Future;Ganglion Cell Layer;Germany;Gestational Age;Goals;Head;high risk;high risk infant;Image;Impairment;improved;indexing;individualized medicine;Infant;Inpatients;Intensive Care;intravitreal injection;Language;Lasers;Life;Lung;macula;Magnetic Resonance Imaging;Measurement;Measures;Microscopic;Motor;Neonatal;neonatal period;neonate;Nervous System Disorder;neurodevelopment;Neurodevelopmental Impairment;neuroimaging;Neurologic;Newborn Infant;Operative Surgical Procedures;Optical Coherence Tomography;Outcome;Oxygen;Patient Care;Patient-Focused Outcomes;Phase;Population;postnatal;postnatal period;Predictive Value;premature;Premature Birth;Premature Infant;preterm newborn;Reporting;response;Retina;retina blood vessel structure;retinal nerve fiber layer;Retinopathy of Prematurity;Risk;School-Age Population;Secondary to;Severities;supplemental oxygen;Testing;Thick;Thinness;tomography;treatment effect;Treatment Factor;treatment risk;ultrasound;Vascular blood supply;Vascular Endothelial Growth Factors;Vision;Visual;Visual Acuity;Visual impairment;Vulnerable Populations

PROJECT_TITLE: Neonatal Optical Coherence Tomography Angiography to Assess the Effects of Postnatal Exposures on Retinal Development and Predict Neurodevelopmental Outcomes

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 2 Study Section[PED2]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cannabinoid Research;Clinical Research;Drug Abuse (NIDA only);Endocannabinoid System Research;HIV/AIDS;Infectious Diseases;Mental Health;Natural Products;Neurosciences;Substance Misuse

ORG_CITY: LA JOLLA

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Despite advances in therapy, people with HIV (PWH) continue to experience adverse health consequences, which appear to be due in part to inflammation that persists even after viral replication is suppressed. Cannabis can reduce inflammation and PWH use it more frequently than people without HIV but little is known about its beneficial and detrimental effects in this population. The proposed translational, multimodal research project seeks to address key scientific gaps to identify the biological mechanisms underlying the effects of cannabis use on persistent inflammation in PWH and its corresponding impact on the medical, neuropsychiatric, and neurocognitive consequences of HIV disease.

PI_NAMEs: IUDICELLO, JENNIFER E (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: 2-arachidonylglycerol;Acquired Immunodeficiency Syndrome;Address;Adverse event;Affect;anandamide;Anti-Inflammatory Agents;Antiinflammatory Effect;antiretroviral therapy;Biological;Biological Markers;Blood;Blood specimen;Body Fluids;Brain;Brain imaging;Cannabidiol;cannabinoid receptor;Cannabinoids;Cannabis;Cell Culture Techniques;Cell surface;Central Nervous System;Cerebrospinal Fluid;Chronic;Clinical;CNR1 gene;CNR2 gene;cohort;Cohort Studies;Collection;comorbidity;Consequences of HIV;cytokine;Data;Disease;Dose;Emotions;Endocannabinoids;endogenous cannabinoid system;Enzymes;Etiology;Experimental Models;experimental study;Family;fatty acid amide hydrolase;Frequencies;Functional disorder;General Population;glial activation;Health;HIV;HIV Infections;HLA-DR Antigens;Immune;immune activation;Immune response;in vivo;Inflammasome;Inflammation;Inflammatory;inflammatory modulation;Inflammatory Response;insight;Interleukin-6;Knowledge;Label;Link;Macrophage Activation;marenostrin;marijuana use;marijuana user;Measurement;Measures;Mediating;Medical;Mental Depression;Methods;Microglia;Monoacylglycerol Lipases;monocyte;multimodality;Myelogenous;Nausea;Neurocognitive;Neurocognitive Deficit;Neurodegenerative Disorders;neuroinflammation;neuropsychiatry;Noise;novel;Organ;organ injury;Outcome;Pain;Participant;Pathway interactions;Persons;Pharmaceutical Preparations;Population;Positron-Emission Tomography;Prevalence;Primary Cell Cultures;Proteins;Psychological Stress;radiotracer;receptor;receptor expression;Research;Research Priority;Research Project Grants;response;Risk;RNA;Role;Sampling;sex;Signal Transduction;Source;Specimen;Standardization;Stress;Tetrahydrocannabinol;Therapeutic;treatment strategy;TREM2 gene;Variant;Virus Replication

PROJECT_TITLE: Cannabis, inflammation, and the brain in persons with HIV


NIH_SPENDING_CATS: Biotechnology;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Project Narrative The proposed research seeks knowledge that will inform effective strategies for a vaccine that protects against HIV-1 by inducing broadly active neutralizing antibodies, and for using such antibodies optimally to treat infection. The research is therefore relevant to public health because, according to UNAIDS, as of 2021 38 million people were living with HIV, of whom 10 million lacked access to antiretroviral therapy, while 1.5 million people became newly infected with the virus and 650,000 died from AIDS and related illnesses that year. The application focuses on the molecular basis of the binding by neutralizing antibodies in relation to their breadth and efficacy of action, aiming to inform not only vaccine development but also the use of neutralizing antibodies to treat or prevent infection.

PI_NAMEs: MOORE, JOHN P (contact)

PROGRAM_OFFICER_NAME: MALASPINA, ANGELA

PROJECT_TERMS: 2019-nCoV;Acquired Immunodeficiency Syndrome;Active Immunization;Affinity;Animal Model;Animals;Antibodies;Antibody Formation;Antibody Response;Antibody Therapy;antiretroviral therapy;Autologous;autoreactivity;B-Cell Activation;B-Cell Antigen Receptor;base;Binding;Biological Assay;C-terminal;Cell surface;central tolerance;Characteristics;Complement;Complementarity Determining Regions;COVID-19 mortality;cross reactivity;crosslink;Cytoplasmic Tail;Data;Databases;density;design;Development;Dimensions;Disease;Dissection;Docking;Endosomes;Entropy;Epithelial Cells;Epitopes;Fingerprint;fitness;Germ Lines;Glycoproteins;Goals;Growth;Heterogeneity;HIV;HIV resistance;HIV-1;HIV-1 vaccine;Human;Immunization;Immunize;Immunoglobulin Somatic Hypermutation;improved;in silico;In Vitro;Individual;Infection;Infection prevention;instrument;Kinetics;Knowledge;large datasets;Length;Link;Measures;Membrane;Methods;Molds;Molecular;Molecular Conformation;mosaic;mutant;nanoparticle;neglect;neoantigens;neutralizing antibody;pandemic disease;Passive Immunization;Passive Immunotherapy;Patients;Peptides;peripheral tolerance;Persons;Polysaccharides;prevent;Preventive;Property;Proteins;PTPRC gene;Public Health;receptor;Remission Induction;Research;Resistance;response;RNA vaccination;SARS-CoV-2 infection;stoichiometry;Surface;Surface Plasmon Resonance;T-Lymphocyte;Techniques;Therapeutic;usability;Vaccination;vaccination strategy;vaccine development;Vaccines;Variant;Viral;Viral Proteins;Viral reservoir;viral resistance;Virion;Virus;Virus-like particle

PROJECT_TITLE: Neutralization of primary HIV-1 viruses

STUDY_SECTION: HIVD

STUDY_SECTION_NAME: HIV Immunopathogenesis and Vaccine Development Study Section[HIVD]


ADMINISTERING_IC: OD

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cardiovascular;Diabetes;Mental Health;Neurosciences;Nutrition;Social Determinants of Health;Women's Health Research

ORG_CITY: FORT COLLINS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: Project Narrative Individuals suffering from metabolic dysfunction are at an increased risk of cardiovascular disease, diabetes, and depression, all of which correlate with increased mortality and years lived with disability and, importantly, are influenced by factors such as chronic stress. This proposal will determine whether activation of a specific frontal cortex to brainstem circuit mitigates the effects of chronic stress on glucose homeostasis and Hypothalamic-Pituitary-Adrenal axis activation. Determining the neurocircuitry that regulates blood glucose during prolonged stress is vital to advance our understanding and, potentially, address the increasingly prevalent stress-related metabolic disorders that burden our society.

PI_NAMEs: DEARING, CARLEY  (contact)

PROGRAM_OFFICER_NAME: TANDON, RITESH

PROJECT_TERMS: Acute;acute stress;Address;Angiotensin II;Animals;Bilateral;biological adaptation to stress;Blood Glucose;blood glucose regulation;Blood Pressure;Blood specimen;Body Temperature;Body Weight;Brain Stem;Cannulas;cardiometabolic risk;Cardiovascular Diseases;cardiovascular disorder risk;career;Cause of Death;Chronic;Chronic stress;Code;cognitive process;Corticosterone;Corticotropin-Releasing Hormone;Data;Diabetes Mellitus;disability;Disease;Doctor of Philosophy;Eating;economic impact;Endocrine;Environment;Epidemic;Epidemiology;Exposure to;Fellowship;Female;Fiber Optics;frontal lobe;Future;Glucagon;Glucocorticoids;Glucose;Glucose Intolerance;Glucose tolerance test;Glutamates;Goals;Health;Heart Rate;hemodynamics;Homeostasis;Hormones;Hypothalamic structure;hypothalamic-pituitary-adrenal axis;Immunohistochemistry;Impairment;Individual;insight;Insulin;Knowledge acquisition;knowledge base;Link;male;Measures;Mental Depression;Messenger RNA;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolic hormone;Metabolism;mortality;neural;neural circuit;Neuroendocrinology;neuromechanism;novel;optogenetics;Pathogenesis;Personal Satisfaction;Physiological;Physiology;Positioning Attribute;Predisposition;Prefrontal Cortex;Preparation;Process;programs;psychologic;Psychological Stress;psychological stressor;Quality of life;Randomized;Rattus;Research;Research Personnel;response;restraint;Role;Science;Scientist;sex;Sex Differences;Signal Transduction;skills;Societies;socioeconomics;Stress;stress reactivity;stress reduction;stressor;Students;Synapses;Testing;Time;Training;Viral Packaging;years lived with disability

PROJECT_TITLE: Sex differences and metabolic responses to chronic stress

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F06-V(20)L]


ADMINISTERING_IC: HL

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: American Indian or Alaska Native;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Sleep Research

ORG_CITY: BOZEMAN

ORG_NAME: MONTANA STATE UNIVERSITY - BOZEMAN

ORG_STATE: MT

PHR: This project will investigate traditional sleep routines and the current sleep environment in American Indian children to develop a culturally appropriate and novel sleep intervention to increase total sleep time for families with K-1st grade children. The outcomes of this study will provide a comprehensive understanding of a relatively unknown behavior (sleep) in American Indians, show results from a novel sleep intervention in a high risk and underserved population, and will also contribute to the research and training development of an American Indian investigator, all defined missions of NHLBI.

PI_NAMEs: GRANT, VERNON MATTHEW (contact)

PROGRAM_OFFICER_NAME: DIXIT, SHILPY

PROJECT_TERMS: Accelerometer;Address;adequate sleep;Adherence;Adult;Age;Alaska Native;American Indian community;American Indian Population;American Indian Tribe;American Indians;Area;Beds;Behavior;Biomedical Research;Blackfeet;Body mass index;Businesses;career;career development;Cellular Phone;Child;Child Development;Child Health;Childhood;Chronic Disease;Clinical Research;Communities;community advisory board;community based participatory approach;community based participatory research;community college;Coupled;cultural values;Data;Dedications;design;Development;diaries;Diet;Disparity;Elderly;Ensure;Environment;evidence base;experience;Facebook;Faculty;Family;family structure;Family Study;Feasibility Studies;feasibility testing;first grade;Focus Groups;follow-up;Fostering;Funding;Goals;Health;Health Disparities Research;health disparity;high risk;Home;Hour;Human Resources;improved;improvement on sleep;Indian reservation;Individual;Intervention;intervention delivery;Intervention Studies;Interview;Laboratories;Language;Learning;Link;Literature;Measures;Mediator;meetings;member;Mentored Research Scientist Development Award;Mentors;Mission;Montana;National Heart, Lung, and Blood Institute;novel;nutrition;obesity risk;Outcome;Outcome Study;Participant;Physical activity;pilot test;Pittsburgh Sleep Quality Index;Play;poor sleep;Population;Positioning Attribute;post intervention;Prevalence;primary outcome;Privatization;Public Health;Randomized, Controlled Trials;Recommendation;Records;recruit;Reporting;Research;Research Methodology;Research Personnel;Reservations;Resources;Risk Factors;Role;Rural health equity;school district;Schools;Scientist;secondary outcome;Shapes;Sleep;sleep behavior;Sleep Deprivation;Sleep Disorders;sleep pattern;social media;Stress;Structure;Surveys;teacher;Testing;Text;Text Messaging;Time;Training;translational research program;Trauma;trend;tribal community;Tribes;tv watching;Underserved Population;United States National Institutes of Health;Universities;urban Native American;Work

PROJECT_TITLE: Developing, implementing, and evaluating a mixed-methods community-based participatory research sleep intervention in families with K-1st grade children living on the Blackfeet Indian Reservation

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(OA)]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Cardiovascular;Digestive Diseases;Genetics;Heart Disease;Liver Disease;Substance Misuse

ORG_CITY: NEW ORLEANS

ORG_NAME: LSU HEALTH SCIENCES CENTER

ORG_STATE: LA

PHR: The chronic abuse of alcohol causes alcoholic cardiomyopathy, which is characterized by cardiac fibrosis and heart failure. Treatment and prevention strategies are limited, as the damaging cardiac effects of chronic alcohol abuse are poorly understood. Our studies will identify key mechanisms of alcohol-induced fibrosis and cardiac dysfunction, which can then be targeted for therapeutic benefit.

PI_NAMEs: BYSANI, CHANDRASEKAR ;GARDNER, JASON DAVIN (contact)

PROGRAM_OFFICER_NAME: PERRUCCIO, ELIZABETH M

PROJECT_TERMS: 5' Untranslated Regions;Adrenergic Agents;Adrenergic beta-Agonists;Alcohol abuse;Alcoholic Cardiomyopathy;Alcohols;Animal Model;Apoptosis;Attenuated;bile duct;Binding;Cardiac;Cardiac Myocytes;Cardiomyopathies;cardioprotection;Chronic;Clinical;Clinical Treatment;Collagen;coronary fibrosis;crosslink;Data;Deposition;Development;Dilated Cardiomyopathy;Dimensions;drug-like compound;Ethanol;Fibrillar Collagen;Fibroblasts;Fibrosis;Functional disorder;Genetic;Genetic Models;Genetic study;Goals;heart damage;Heart failure;Heart Injuries;Heavy Drinking;Hepatic Stellate Cell;high throughput screening;Hypertension;Hypertrophy;Impairment;In Vitro;in vivo;Inflammation;Infusion procedures;interstitial;Intervention;Intervention Studies;Isoproterenol;Knock-in;Knock-in Mouse;Left;Left Ventricular Ejection Fraction;Ligation;Liver Fibrosis;Messenger RNA;Modeling;mouse model;Mus;Mutant Strains Mice;Mutate;Myocardial dysfunction;National Institute on Alcohol Abuse and Alcoholism;new therapeutic target;novel;Outcome Measure;Oxidative Stress;pharmacologic;posttranscriptional;Pre-Clinical Model;prevent;Prevention strategy;prophylactic;protein expression;Publishing;Rattus;Regulation;Resistance;response;Ribonucleoproteins;Risk;RNA-Binding Proteins;Role;small molecule inhibitor;stem;Stress;Structure;targeted treatment;Testing;Therapeutic;Therapeutic Uses;treatment strategy;vapor;Ventricular;Wild Type Mouse

PROJECT_TITLE: Role of novel RNA binding protein LARP6 in alcoholic cardiomyopathy

STUDY_SECTION: AA

STUDY_SECTION_NAME: Biomedical Research Study Section[AA-1]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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;Biodefense and Related Countermeasures;Biomedical Imaging;Biotechnology;Brain Disorders;Dementia;Emerging Infectious Diseases;Genetics;Infectious Diseases;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Vector-Borne Diseases;Zika Virus

ORG_CITY: SAINT LOUIS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: NARRATIVE Neurotropic RNA viruses continue to emerge at an increasing rate, causing severe acute neuroinvasive syndromes with majority of survivors exhibiting significant neurocognitive deficits that persist for years after clearance of virus. Most of these are vector-borne infections, however, the most recently emerged RNA viruses, Zika virus and severe acute respiratory syndrome coronavirus (SARS-CoV)-2, can be transmitted person-to-person. In addition, evidence that viruses trigger the development of neurodegenerative diseases, such as Alzheimer's disease and other dementias, is mounting. There are limited studies of the mechanisms of post-infectious, progressive pathological forgetting, which are poorly understood. There are also currently no diagnostic or treatment modalities for cognitive sequelae in patients that recover from viral infections of the central nervous system,.

PI_NAMEs: CAIN, MATTHEW D (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: 2019-nCoV;Acute;adult neurogenesis;Alzheimer's Disease;Area;Astrocytes;Award;Binding;Biological Markers;Bone Marrow;Calcium;Cell Communication;cell type;Cells;Central Nervous System Viral Diseases;chemokine receptor;Chimera organism;Clinical Trials;Cognitive;Complement;cytokine;Cytokine Receptors;Dementia;Detection;Development;Diagnostic;diagnostic tool;Disease;Exhibits;Flavivirus;forgetting;Gene Targeting;Generations;Genes;Genetic;genetic approach;Hemoglobin;Image;Immune;Immunology;Impaired cognition;in vivo;Infiltration;Inflammasome;innate immune mechanisms;Laboratories;Learning;Magnetic Resonance Imaging;Maintenance;Maps;Mediating;Mediator;Memory;Memory Disorders;Methods;Microglia;Modality;Modeling;Molecular;Mononuclear;mouse model;multidisciplinary;Mus;Myeloid Cells;National Institute of Neurological Disorders and Stroke;Nerve Degeneration;nerve stem cell;Nervous System;Neurocognitive Deficit;Neurodegenerative Disorders;neuroimaging;Neuroimmune;neuroimmunology;Neurons;Neurosciences;neurotoxic;neurotropic;novel;Optics;pathogen;Pathologic;Pathway interactions;Patient Monitoring;Patients;Persons;pharmacologic;Positron-Emission Tomography;Process;programs;Progressive Disease;Receptor Signaling;Recovery;Regulation;repaired;Reporter;Research;response;Risk;Risk Factors;RNA Viruses;Role;Signal Transduction;single-cell RNA sequencing;stem cell fate;Structure;Survivors;Synapses;Syndrome;T-Lymphocyte;Therapeutic;tissue resident memory T cell;tool;transmission process;vector-borne infection;virology;Virus;Virus Diseases;West Nile virus;Zika Virus

PROJECT_TITLE: Research Program Award (R35 Clinical Trial Optional) - Dr. Robyn Klein NINDS


ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Relevance The proposed research will elucidate mechanisms by which atherosclerosis can be regulated by small nucleolar RNAs that affect cellular levels of reactive oxygen species. Understanding the function of small nucleolar RNAs in vascular smooth muscle cells and in macrophages may lead to new therapeutic interventions to treat atherosclerosis, which is the leading cause of heart attack and stroke. Thus, the proposed research is relevant to NIH’s mission of developing fundamental knowledge that will help reduce the burdens of illness and disability.

PI_NAMEs: FREEDMAN, NEIL J. (contact);HOLLEY, CHRISTOPHER LEE

PROGRAM_OFFICER_NAME: PLAYFORD, MARTIN P

PROJECT_TERMS: Adverse effects;Affect;Age;Antiatherogenic;Antioxidants;Antisense Oligonucleotides;Aorta;Apolipoprotein E;Arteries;atherogenesis;Atherosclerosis;Binding;Bone Marrow;Bone Marrow Cells;Bone Marrow Transplantation;burden of illness;Carotid Arteries;catalase;cell motility;Cell Proliferation;Cells;Clinical Trials;cohort;congenic;Congenic Mice;crosslink;cytochrome c oxidase;disability;Embryo;Enzymes;fibrillarin;Foam Cells;Genetic;Genetic Complementation Test;Goals;Guide RNA;Hepatic;Human;Hybrids;Immunity;In Vitro;in vivo;Infection;Inflammation;Inflammatory;Insulin Resistance;Introns;Knowledge;Lecithin;Ligation;Listeriosis;Macrophage;Maps;Mediating;Messenger RNA;Methods;Methylation;Methyltransferase;Mission;Mitochondria;Molecular Chaperones;mRNA Precursor;Mus;Mutagenesis;Myocardial Infarction;NADPH Oxidase;new therapeutic target;novel;novel therapeutic intervention;Oxidases;Oxidative Stress;oxidized low density lipoprotein;Predisposition;Process;Production;protein expression;Protein Isoforms;Proteins;Reactive Oxygen Species;recruit;Research;Ribosomal Proteins;Ribosomal RNA;RNA;Role;Signal Transduction;Site;Small Interfering RNA;Small Nucleolar RNA;Smooth Muscle Myocytes;Stroke;Superoxides;Testing;Tissues;TNF gene;transcriptome;transdifferentiation;Transgenes;Translations;Transplantation;United States National Institutes of Health;Untranslated RNA;Vascular Smooth Muscle;western diet

PROJECT_TITLE: Mechanisms by which Small Nucleolar RNAs Exacerbate Atherosclerosis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


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

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE CAR T cell therapy has revolutionized the treatment of relapsed/refractory B cell malignancies, but most people treated with CAR T cells don’t have durable responses, indicating that to improve CAR T cell therapy, we need better tools to measure how patients are responding. Existing tools to monitor a patient's cellular and molecular immune response to CAR T cell therapy are limited, so we developed antigen-multimer technology, which outperforms most available reagents in CAR T-cell labeling, and is useful in CAR T-cell detection, isolation, and downstream phenotypic and functional analyses. In this application, we propose to demonstrate the flexibility and broad applicability of antigen-multimer technology in labeling four different CARs, and by applying these reagents to analyze patient biospecimens using single-cell multicolor flow cytometry and multi-omics analyses.

PI_NAMEs: HUANG, JUN  (contact);KLINE, JUSTIN P.

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: Affinity;antigen detection;Antigens;Autologous;Avidity;B lymphoid malignancy;B-Cell Acute Lymphoblastic Leukemia;B-Cell Lymphomas;Binding;biobank;Biological Assay;Biopsy;Biopsy Specimen;Blood;Blood specimen;cancer cell;CAR T cell therapy;CD19 gene;Cell Count;Cell Physiology;Cell Separation;Cell Therapy;Cells;Cellular biology;chimeric antigen receptor;chimeric antigen receptor T cells;Clinic;Clinical;clinical application;Color;cost;cytokine;Cytolysis;Data;Detection;Development;Drug Industry;Engineering;Epidermal Growth Factor Receptor;epigenome;ERBB2 gene;experience;experimental study;flexibility;Flow Cytometry;Formulation;Glycosides;Immune response;immunoengineering;improved;In complete remission;in vivo;Industry;Infusion procedures;Knowledge;Label;large cell Diffuse non-Hodgkin's lymphoma;Lymphoma;Malignant Neoplasms;Mantle Cell Lymphoma;Measures;Mediating;mesothelin;Molecular;Monitor;Monoclonal Antibodies;monomer;Multiomic Data;Multiple Myeloma;multiple omics;Nature;patient population;Patients;peripheral blood;Persons;Phenotype;preclinical study;profiles in patients;Property;Proteome;Reagent;receptor expression;Refractory;Relapse;Research;Research Personnel;Resolution;responders and non-responders;response;Sampling;Scientist;single cell analysis;Solid Neoplasm;Sorting;Specificity;Stains;success;Surface Antigens;T cell differentiation;Technology;Testing;Therapeutic Studies;Time;tool;transcriptome;Treatment Efficacy;treatment response;tumor;Tumor Antigens;Variant;War;weapons

PROJECT_TITLE: Development of antigen multimers for CAR T cell detection and functional profiling

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Emerging Infectious Diseases;Infectious Diseases;Prevention;Rare Diseases;Tuberculosis

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE Tuberculosis is a leading infectious killer worldwide. TB preventive therapy (TPT) is highly efficacious but poorly implemented. New shorter regimens that have better adherence and safety are now available and can contribute to epidemic control. We plan to conduct a randomized trial of one-month of daily rifapentine and isoniazid compared with three months of the same drugs given weekly in people without HIV infection to determine adherence to and safety of these regimens. We will also assess the cost-effectiveness of these two regimens.

PI_NAMEs: CHAISSON, RICHARD E. (contact)

PROGRAM_OFFICER_NAME: LAUGHON, BARBARA E

PROJECT_TERMS: Adherence;Adolescent;Adult;Adverse event;Biological;Cause of Death;Child;clinical practice;Clinical Trials;comparative cost effectiveness;Consumption;cost;Cost Analysis;cost effectiveness;Cost Savings;Data;Development;discontinuation study;Disease;Dose;efficacy study;Epidemic;epidemic response;Event;Exanthema;experience;Fever;Goals;Guidelines;Hepatotoxicity;high risk;high risk population;HIV;HIV Infections;HIV Seronegativity;HIV Seropositivity;Hypersensitivity;Immunosuppression;Incidence;incremental cost-effectiveness;Individual;innovation;Intervention;isoniazid;Meta-Analysis;Modeling;Monitor;mortality risk;mouse model;National Institute of Allergy and Infectious Disease;Nausea and Vomiting;novel;pathogen;patient population;Patient Self-Report;Patients;Peripheral Nervous System Diseases;Persons;Pharmaceutical Preparations;pharmacologic;pill;Population;Populations at Risk;prevent;Prevention;Preventive therapy;Pyrazinamide;Randomized;randomized trial;Recommendation;Regimen;Research;Research Personnel;Rifampin;Rifamycins;rifapentine;Risk;Safety;side effect;Study models;success;Syndrome;Therapy trial;Time;Toxic effect;treatment comparison;trial comparing;Tuberculosis;United States National Institutes of Health;uptake;Work;World Health Organization

PROJECT_TITLE: Safety and Tolerability of Ultra-short Course Rifapentine and Isoniazid (1HP) for Prevention of Tuberculosis in HIV-Uninfected Individuals


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Chronic Pain;Clinical Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pain Research;Telehealth

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE This proposal investigates statistical models to inform the design, development, and evaluation of mobile health (mHealth) measures using patient generated health data with high complexity and temporality. We ground our investigation in chronic pelvic pain as the disease model, a complex disorder with high societal burden and impact on Quality of Life. We will investigate models that can handle the inherent challenges in self-tracking data to derive ecologically valid and actionable patient outcome measures.

PI_NAMEs: ENSARI, IPEK  (contact)

PROGRAM_OFFICER_NAME: AHN, HELENA HYESOOK

PROJECT_TERMS: Abdominal Pain;Address;analytical method;Benchmarking;Biological Markers;Chronic;chronic pelvic pain;Clinical;clinical decision-making;Complex;computerized tools;Control Groups;daily functioning;Data;Data Analyses;Data Analytics;data modeling;data streams;design;Development;Dimensions;Disease;Disease Management;disease model;Disease Outcome;endometriosis;Enrollment;Evaluation;evidence base;Fibroid Tumor;flexibility;Generations;Health;health assessment;Health behavior;health data;Heterogeneity;improved;improved outcome;Individual;Inflammatory;interest;Investigation;Investments;Length;Location;Measures;Methods;mHealth;Mobile Health Application;Modeling;Monitor;Nature;novel;novel strategies;Outcome;Outcome Measure;outcome prediction;Output;Pain;Pain Disorder;Pain Measurement;pain patient;pain symptom;Participant;Pathology;patient engagement;Patient Self-Report;Patient-Focused Outcomes;Patients;Pelvic Pain;Persons;Pharmaceutical Preparations;Physical therapy;Prediction of Response to Therapy;predictive modeling;Prevalence;Productivity;Quality of life;Research;response;Sampling;Self Management;Series;Severities;Sleep;Specificity;Statistical Models;Strategic Planning;Structure;supervised learning;Symptoms;Techniques;Technology;Testing;Time;tool;Translations;Treatment outcome;treatment response;United States National Library of Medicine;unsupervised learning;Variant;Work

PROJECT_TITLE: Evaluation techniques for mHealth outcome measures using patient generated health data

STUDY_SECTION: CIDH

STUDY_SECTION_NAME: Clinical Informatics and Digital Health Study Section[CIDH]


NIH_SPENDING_CATS: Asthma;Infectious Diseases;Lung

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative: Rhinovirus-induced exacerbations of asthma represent a significant health burden to children and adults, and pose a significant challenge in controlling and preventing asthma-related deaths. The molecular mechanisms by which rhinovirus decreases efficacy of current therapeutics used to treat asthma and exacerbations of the disease are unclear. Current asthma therapies dampen inflammation, and/or promote opening and reduce bronchoconstriction of airway smooth muscle that modulates tone of the airway. Our preliminary data suggests that rhinovirus exposure of epithelial cells that line the airways results in decreased bronchodilator responses in airway smooth muscle. Our proposal aims to identify novel therapeutic targets to reverse rhinovirus-induced hyposensitivity to bronchodilators, that when given with current bronchodilators would thereby allow these therapeutics to work more effectively in treatment of virus-induced asthma exacerbations.

PI_NAMEs: KOZIOL-WHITE, CYNTHIA  (contact)

PROGRAM_OFFICER_NAME: LIU, QIAN

PROJECT_TERMS: Actins;Acute;Adenosine Diphosphate;ADRBK1 gene;Adult;Affect;Agonist;Air;Airway Disease;airway epithelium;airway hyperresponsiveness;airway inflammation;airway obstruction;Arrestin Beta 1;Asthma;asthma exacerbation;Attenuated;attenuation;beta-2 Adrenergic Receptors;Bronchoconstriction;Bronchodilation;Bronchodilator Agents;Calcium;Cell Line;Cell Physiology;Cells;Cessation of life;Child;Clinical;Coculture Techniques;constriction;Coupled;CXCR4 gene;CXCR4 Receptors;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Data;Development;Disease;Effector Cell;Epithelial Cells;Epithelium;exposed human population;Exposure to;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;gastrointestinal epithelium;GTP-Binding Protein alpha Subunits, Gs;GTP-Binding Proteins;Health;Host Defense;Human;Immunity;Impairment;Infection;Inflammation;Inflammation Mediators;inhibitor;knock-down;Liquid substance;loss of function;Lung;Mediating;Mediator;MMP9 gene;Modeling;Molecular;Morbidity - disease rate;mortality;Muscle Contraction;Muscle relaxation phase;Myosin Light Chains;Natural regeneration;new therapeutic target;novel;PAR-2 Receptor;Pathway interactions;Patients;Phenotype;phosphoric diester hydrolase;Phosphorylation;Phosphotransferases;Pre-Clinical Model;prevent;Production;Productivity;Prostaglandins;Proteinase-Activated Receptors;Proteins;Publishing;receptor;receptor coupling;receptor function;reduce symptoms;Relaxation;release factor 3;repaired;Research;respiratory smooth muscle;response;Rhinovirus;Rhinovirus infection;Rho-associated kinase;Role;Signal Induction;Signal Pathway;Signal Transduction;Signaling Molecule;Slice;Small Interfering RNA;Smooth Muscle;Smooth Muscle Myocytes;Symptoms;System;Therapeutic;therapeutic target;Therapeutic Uses;trefoil factor;Up-Regulation;VEGF165;Viral;Viral Respiratory Tract Infection;Virus;Work

PROJECT_TITLE: Rhinovirus, airway smooth muscle, and mechanisms of irreversible airflow obstruction

STUDY_SECTION: LCMI

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


NIH_SPENDING_CATS: Clinical Research;Kidney Disease;Pediatric;Urologic Diseases

ORG_CITY: Columbus

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE This proposal seeks to provide a transformative 12-week summer research program for medical and graduate students that will encourage them to pursue careers in kidney and urinary tract related research and clinical programs. This program is also designed to attract minorities and students from underserved and disadvantaged communities with the long-term goal of increasing and diversifying the number of physician-scientists and basic- scientists submitting grant applications to the NIDDK in the fields of nephrology and urology.

PI_NAMEs: MCHUGH, KIRK M. (contact);SPENCER, JOHN DAVID

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Address;American;Applications Grants;career;career development;Caring;Childhood;Chronic Kidney Failure;Clinical Research;Data;Development;Disease;doctoral student;Education;education research;End stage renal failure;experience;Goals;graduate student;Grant;innovation;interest;Kidney;Kidney Diseases;Medical Students;National Institute of Diabetes and Digestive and Kidney Diseases;Nephrology;next generation;Ohio;Pediatric Hospitals;Persons;Physicians;Population;pre-doctoral;programs;Research;Resources;Scientist;Structure;Students;summer research;Training Programs;Translational Research;trend;United States National Institutes of Health;Universities;Urinary tract;Urologic Diseases;Urology

PROJECT_TITLE: Student Urinary Tract Program in Education and Research (SUPER) Summer Training Program

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK(M1)-1-B]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Networking and Information Technology R&D (NITRD)

ORG_CITY: PROVO

ORG_DEPT: BIOLOGY

ORG_NAME: BRIGHAM YOUNG UNIVERSITY

ORG_STATE: UT

PHR: Single-cell proteomics (SCP) has potential to revolutionize biologist’s understanding of how individual cells function in complex systems. SCP in its current state provides a shallow profile of cellular proteins and quantitative values with high variance. This proposal describes the first ever dedicated software for SCP analysis and should greatly improve sensitivity for peptide detection and improve accuracy for quantification.

PI_NAMEs: PAYNE, SAMUEL H (contact);SHORTREED, MICHAEL R

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Algorithms;Atlases;Benchmarking;Biological Process;Categories;Cell Physiology;cell type;Cells;Characteristics;Complex;computational atlas;Computer software;computerized tools;cost;Coupled;Data;data acquisition;data archive;Dedications;design;Detection;Environment;expectation;Feedback;Goals;Heterogeneity;improved;Individual;instrumentation;Ions;Label;Laboratories;Libraries;Life;Link;mass spectrometer;Mass Spectrum Analysis;Metabolic;Nature;Neurons;Noise;novel;Peptides;Performance;Preparation;Proteins;Proteome;Proteomics;Proxy;Research;RNA;Sampling;Signal Transduction;single cell analysis;single-cell RNA sequencing;software development;Software Tools;Spinal Cord;supervised learning;System;Technology;Tissues;Transcript;transfer learning;Work

PROJECT_TITLE: Enhanced Sensitivity and Quantitative Precision for Single Cell Proteomics

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Immunotherapy;Skin Cancer

PHR: PROJECT NARRATIVE Cancer remains the second leading cause of mortality in the United States. While immunotherapies, including checkpoint inhibitors hold great promise, most patients do not respond to immunotherapy and resistance mechanisms are incompletely defined. This proposal will use genetic murine tumor models to determine the mechanistic role of tumor cell-intrinsic hypoxia inducible factor (HIF)-1α and HIF-2α activation in impairing the anti-tumor T cell response within the tumor microenvironment and promoting immunotherapy resistance.

PI_NAMEs: TRUJILLO, JONATHAN A (contact)

PROGRAM_OFFICER_NAME: BOULANGER-ESPEUT, CORINNE A

PROJECT_TERMS: Ablation;Adoptive Transfer;anti-CTLA-4 therapy;anti-CTLA4 antibodies;anti-PD-L1;anti-tumor immune response;Antibody Therapy;Antigen Presentation;antigen-specific T cells;Apoptosis;Award;Bioinformatics;cancer cell;cancer genomics;cancer infiltrating T cells;cancer type;career;career development;Cell Physiology;Cell Survival;chemokine;Chicago;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Coupled;CTLA4 blockade;Data;Defect;Dendritic Cells;Development Plans;Doctor of Philosophy;draining lymph node;effector T cell;engineered T cells;Exclusion;experimental study;Failure;Flow Cytometry;Gene Expression Profiling;Genes;Genetic;Genetic Transcription;Genetically Engineered Mouse;Genomics;Goals;Hematology;Human;Hypoxia;Hypoxia Inducible Factor;immune activation;immune cell infiltrate;immune checkpoint blockade;Immune checkpoint inhibitor;Immune Evasion;Immunofluorescence Immunologic;Immunologics;Immunotherapeutic agent;Immunotherapy;Impairment;improved outcome;in vivo;Infiltration;Inflammation;inhibitor;instructor;International;Invaded;K-Series Research Career Programs;Knowledge;Link;loss of function;Malignant Neoplasms;Mediating;Melanoma;Melanoma Cell;Mentors;Metabolic;migration;Modeling;mortality;mouse model;Mus;Neoplasm Metastasis;neoplastic cell;novel;Oncogenes;Oncogenic;Oncology;Pathway interactions;Patient-Focused Outcomes;Patients;PD-1 blockade;Physicians;Play;programmed cell death protein 1;programs;Proliferating;PTEN gene;recruit;Renal Cell Carcinoma;Research;Resistance;resistance mechanism;response;restraint;Role;Scientist;Series;Signal Induction;single-cell RNA sequencing;success;System;T cell infiltration;T cell response;T-Cell Receptor;T-Lymphocyte;Techniques;Testing;Therapeutic;trafficking;Training;transcription factor;transcriptome sequencing;transcriptomics;Transplantation;tumor;Tumor Escape;Tumor Expansion;Tumor Immunity;tumor immunology;tumor microenvironment;Tumor Promotion;Tumor Tissue;United States;Universities;Variant

PROJECT_TITLE: Elucidating the role of tumor cell-intrinsic hypoxia inducible factor (HIF)-1α and HIF-2α pathway activation in tumor immune evasion

STUDY_SECTION: NCI

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


NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Mental Health;Neurosciences;Post-Traumatic Stress Disorder (PTSD);Stimulant Use and Misuse;Substance Misuse

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

PHR: Project Narrative Important discoveries showed that a single traumatic event induces enduring cortico-striatal synaptic plasticity. The proposed experiments will provide insight into how stress disorders permanently alter brain structure and function, and how these changes increase vulnerability to drug use and relapse.

PI_NAMEs: GARCIA KELLER, CONSTANZA  (contact)

PROJECT_TERMS: Acute;acute stress;addiction;Animal Model;Animals;Appointment;avoidance behavior;Behavior;Biological;Brain;cell type;Cells;Characteristics;Chemicals;Chemosensitization;Cocaine;cocaine cue;cocaine seeking;cocaine use;Code;comorbidity;coping;Coping Behavior;Corpus striatum structure;Cues;designer receptors exclusively activated by designer drugs;Diagnosis;Dopamine D2 Receptor;Drug Design;drug relapse;Drug usage;drug use vulnerability;Environment;epidemiology study;Event;Excitatory Synapse;experience;experimental study;Exposure to;Faculty;Glutamates;Goals;Grant;Image;in vivo;Incidence;Individual;insight;Institution;Intake;Integrins;ITGB3 gene;knock-down;Life;Link;LoxP-flanked allele;Mediating;Mentors;Metalloproteases;Molecular;neuroadaptation;neurobiological mechanism;neuromechanism;Neurons;Neurosciences;neurotransmission;novel;Nucleus Accumbens;Odors;Pattern;Pharmaceutical Preparations;Phase;Play;Positioning Attribute;Post-Traumatic Stress Disorders;Postdoctoral Fellow;Predisposition;Prevalence;prevent;programs;Proteins;Publications;Qualifying;Rattus;Recording of previous events;Regulation;Research;response;restraint stress;Role;selective expression;Signal Transduction;small hairpin RNA;Stress;stress disorder;Stressful Event;Structure;Substance Use Disorder;success;Synapses;Synaptic plasticity;Technology;tenure track;Testing;Time;Training;transmission process;Trauma;traumatic event;Treatment outcome

PROJECT_TITLE: Circuit Mechanisms for Conditioned Stress Regulation of Addiction


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

ORG_STATE: MD

PHR: Project Narrative Age-related cognitive deficits are a growing public health problem for our aging society, especially in the Information Age when higher cognitive functions are required to manage finances and medical care and allow people to live independently. The goal of the proposal is to develop brain-penetrant glutamate carboxypeptidase II (GCPII) inhibitors for the treatment of age-related cognitive disorders through novel actions in the association cortex. The successful execution of this project will lead to a novel therapeutic strategy with greater feasibility for clinical translation to address the main healthcare needs of the growing elderly population.

PI_NAMEs: ARNSTEN, AMY F.T.;SLUSHER, BARBARA STAUCH;TSUKAMOTO, TAKASHI  (contact)

PROGRAM_OFFICER_NAME: GROTHAUS, PAUL G

PROJECT_TERMS: Address;Age;age related cognitive disorder;Age-associated memory impairment;aged;Aging;aging brain;Agonist;Agreement;Alzheimer's disease risk;analog;analog L;association cortex;Binding;Brain;Brain Diseases;Brain region;C-terminal;Calcium;Calcium Signaling;Caring;Charge;Chemistry;Clinical;clinical candidate;Clinical Research;clinical translation;Cognition;Cognitive;Cognitive deficits;cognitive enhancement;cognitive function;cognitive testing;Computer Assisted;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Data;design;Development;Dose;Drug Design;drug discovery;Drug Kinetics;efficacy study;efficacy testing;Elderly;Exhibits;extracellular;FOLH1 gene;Glutamates;Goals;Healthcare;Human;immunogenicity;Impaired cognition;improved;In Vitro;in vivo;Inflammation;inhibitor;Late Onset Alzheimer Disease;manufacture;Maryland;Mediating;Medical;Membrane;Memory;metabotropic glutamate receptors type 3;Metalloproteases;Monkeys;N-acetylaspartate;N-acetylaspartylglutamate;Nervous System Disorder;Neurobiology;Neurons;neuroprotection;novel;novel strategies;novel therapeutic intervention;Oral;Oral Administration;Permeability;Persons;pharmacologic;Physiological;Play;Population;positive allosteric modulator;postsynaptic;Potassium Channel;pre-clinical;Prefrontal Cortex;Probability;Prodrugs;Public Health;Rattus;Regimen;Regulation;Research Personnel;Research Proposals;response;Risk Reduction;Role;screening;side effect;Signal Transduction;Societies;success;Sulfhydryl Compounds;tau-1;Testing;Therapeutic;Translating;translation to humans;Zinc

PROJECT_TITLE: Development of GCPII inhibitors for the treatment of age-related cognitive disorders

STUDY_SECTION: DDNS

STUDY_SECTION_NAME: Drug Discovery for the Nervous System Study Section[DDNS-R]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE. Role of XPD in DNA Damage Response Pathway Choice We have discovered that the nucleotide excision repair factor (NER), XPD occupies a pivotal role in mediating survival/death decisions following DNA damage. We will elucidate the mechanism by which XPD influences cellular fate outcomes and determine the role of XPD-mediated pathway choice in maintaining genomic integrity. We expect that this work will provide insight into the regulatory mechanisms that facilitate crosstalk within the DNA damage response network.

PI_NAMEs: ROGERS, FAYE A (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Apoptosis;Apoptotic;cancer risk;Cell Cycle Arrest;Cell Death;Cell Survival;Cells;Cessation of life;Chemicals;chemotherapeutic agent;Complex;crosslink;Data;design;Disease;DNA Damage;DNA lesion;DNA Repair;driving force;Equilibrium;Etiology;experimental study;Exposure to;Funding;Genetic Diseases;Genetic Transcription;Genome;genome integrity;Genome Stability;Genomic Instability;Genotoxic Stress;genotoxicity;Goals;helicase;human disease;Human Genetics;Human Genome;insight;Lesion;Link;Location;Maintenance;Malignant Neoplasms;Mediating;Molecular;mouse model;Mutagenesis;Mutagens;Mutation;novel;Nucleotide Excision Repair;Outcome;Pathway interactions;Phenotype;Phosphorylation;Positioning Attribute;preservation;prevent;Process;programs;Property;Protein Tyrosine Kinase;Proteins;Reaction;recruit;Regulation;repair function;repaired;Research;Research Project Grants;response;Role;Series;Signal Pathway;Signal Transduction;Site;Structure;System;tool;TP53 gene;transcription factor TFIIH;Tyrosine;Tyrosine Phosphorylation;Work

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: RICHMOND

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: NLRP3 inflammasome has recently been suggested to play important roles in multiple human diseases including Alzheimer’s disease (AD). The research proposed in this application will conduct structural optimization of our newly identified lead NLRP3 inflammasome inhibitors to develop a candidate to accomplish IND-enabling studies as potential AD therapeutic agent; therefore it is relevant to public health.

PI_NAMEs: ZHANG, SHIJUN  (contact)

PROGRAM_OFFICER_NAME: REFOLO, LORENZO

PROJECT_TERMS: 3xTg-AD mouse;AD transgenic mice;Adaptor Signaling Protein;Address;Affinity;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease therapeutic;Ames Assay;analog;Animal Disease Models;Animal Model;Binding;Binding Proteins;Binding Sites;Biologic Characteristic;Biological Availability;Biological Products;Biophysics;blood-brain barrier penetration;candidate identification;candidate selection;Canis familiaris;CASP1 gene;Cell Death;cell injury;Cellular Assay;Cellular Stress;chemical synthesis;Chemicals;Clinical;clinical candidate;Clinical Research;Clinical Trials;cognitive function;compound 30;cytokine;Dementia;Dependence;design;Development;Disease;Dose;drug development;drug discovery;Drug Kinetics;Drug Targeting;Evaluation;Family;flexibility;Formulation;Future;Generations;Goals;human disease;IL18 gene;Immunology;improved;in silico;In Vitro;in vivo;Inflammasome;Inflammatory;Inflammatory Response;inhibitor;Innate Immune Response;Interleukin-1 beta;Investigational Drugs;Lead;manufacture;marenostrin;meetings;Metabolic;Methods;microbial products;mouse model;multidisciplinary;Mus;Natural Immunity;Neurodegenerative Disorders;neuroinflammation;Neurology;novel;Oral;Oral Administration;Pathogenesis;patient response;Permeability;Pharmaceutical Chemistry;pharmacologic;Phosphotransferases;Plasma Proteins;Play;pre-clinical;Preventive;Production;Property;protein complex;Proteins;Public Health;Publishing;Rattus;receptor;Regimen;Reporting;Research;Rodent;Role;scaffold;scale up;sensor;small molecule;small molecule libraries;Specificity;Structure-Activity Relationship;Sulfonamides;Testing;Therapeutic;Therapeutic Agents;therapeutic candidate;therapeutically effective;Toxic effect;Toxicology;Validation

PROJECT_TITLE: Development of novel NLRP3 inflammasome inhibitors for intervening in Alzheimer's disease


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Clinical Research;Data Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Social Determinants of Health

ORG_STATE: NY

PI_NAMEs: GABRILOVE, JANICE L (contact);WRIGHT, ROBERT O

PROGRAM_OFFICER_NAME: MERCHANT, CAROL

PROJECT_TERMS: Address;Alzheimer's Disease;anti-racism;Artificial Intelligence;Ascorbic Acid;Big Data;Biochemical;Bioethics;Bioinformatics;Biology;biomedical data science;Biometry;career;career development;Career Mobility;Citric Acid Cycle;Clinical;Clinical Informatics;Clinical Research;Clinical Sciences;Clinical Trials Design;clinically relevant;Collaborations;Communities;Competence;Competency-Based Education;Complex;Computational Biology;COVID-19;Data;Data Science;data science education;Data Scientist;design;Development;Diabetes Mellitus;digital health;Discipline;Disease;Disparity;Doctor of Philosophy;doctoral student;Ecosystem;Education;Educational Curriculum;empowerment;Engineering;Entrepreneurship;Enzymes;Epidemiology;Epigenetic Process;equity, diversity, and inclusion;Ethics;Fellowship;forging;Funding;Genetic;genome sciences;Genomics;Goals;Government;Health;health disparity;health equity;Health Sciences;Health system;Healthcare;Human;implementation science;Individual;individualized prevention;Inequity;innovation;Institution;Interdisciplinary Communication;Justice;Knowledge;Language;Leadership;Learning;life span;Malignant Neoplasms;Medical;Medical Students;Medicine;member;Mentors;Mentorship;Methods;Modeling;Modernization;multidisciplinary;National Center for Advancing Translational Sciences;National Research Service Awards;next generation;novel;patient oriented research;patient population;pedagogy;peer;Phenotype;Physicians;Physiology;post-doctoral training;Postdoctoral Fellow;pre-doctoral;precision medicine;Productivity;programs;recruit;Research;Research Design;Research Personnel;Research Training;resilience;Science;Scientist;skills;Social Responsibility;Statistical Computing;Technology;TNFSF15 gene;tool;Training;Training Activity;Training Programs;Translational Research;translational scientist;Underrepresented Populations;United States National Institutes of Health;Vocabulary;Work

PROJECT_TITLE: J: NRSA Training Core