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

ORG_CITY: MADISON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: NARRATIVE Alzheimer’s disease (AD) biomarkers can convey important temporal information about disease progression. This longitudinal observational study is identifying the earliest detectible signs of this dual proteinopathy and improving the prognostic capability of researchers to predict cognitive decline based on these markers.

PI_NAMEs: JOHNSON, STERLING C (contact)

PROGRAM_OFFICER_NAME: HSIAO, JOHN

PROJECT_TERMS: 4D MRI;Address;Age of Onset;alpha synuclein;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid;Amyloidosis;Atlases;Biological Markers;Blood Vessels;Brain;burden of illness;Characteristics;Chronic;Chronology;Clinical Trials;Cognitive;cohort;Collection;Computational algorithm;Computing Methodologies;Data;Data Sources;Dementia;Dimensions;Disease;Disease Progression;Disease Resistance;dynamic system;Exhibits;follow-up;Funding;Genetic;genome-wide;Genotype;glial activation;Glial Fibrillary Acidic Protein;Goals;Health;Heterogeneity;heuristics;Image;imaging biomarker;Impaired cognition;improved;Individual;insight;Joints;Knowledge;learning strategy;Liquid substance;longitudinal course;Longitudinal, observational study;Magnetic Resonance Imaging;Measures;middle age;Nerve Degeneration;neurogranin;neuronal pentraxin;non-demented;novel;Outcome;Participant;Pathology;Pattern;Persons;Phenotype;Plasma;Populations at Risk;Positron-Emission Tomography;pre-clinical;Prevention Research;Prevention strategy;Process;prognostic;progression marker;Protein Isoforms;rate of change;Recording of previous events;Registries;Research Personnel;Risk;Secondary Prevention;Serial Learning;spatiotemporal;Standardization;Symptoms;tau aggregation;tau Proteins;Time;timeline;tool;Vascular Diseases;willingness;Wisconsin;Work;β-amyloid burden

PROJECT_TITLE: The Longitudinal Course of Imaging Biomarkers in People At Risk for Alzheimer’s Disease

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: EUGENE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: CHEMISTRY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: Project Narrative We propose studying the evolution of innate immune proteins that are key players in healthy and harmful inflammation. Understanding how these proteins evolved will provide insight into how the proteins function, and thus help us better target these proteins for treatment. The proposed work will also provide important insight into how natural proteins evolve new functions.

PI_NAMEs: HARMS, MICHAEL JONATHAN (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TITLE: Evolution of new protein function in the multi-protein, multi-functional Toll-like receptor 4 complex

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: CHICAGO

ORG_DEPT: NEUROLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE: Primary Progressive Aphasia (PPA) is a dementia that undermines word finding and the ability to communicate through the asymmetric degeneration of the language-dominant (usually left) hemisphere of the brain. It can be caused by multiple entities, including Alzheimer's disease (AD) and several forms of frontotemporal lobar degeneration (FTLD). This project, based on a unique group of longitudinally evaluated PPA participants, will explore disease-specific anatomic, cellular and molecular aspects of PPA so that each patient can be approached through principles of personalized medicine that address not only symptoms but also underlying disease types.

PI_NAMEs: MESULAM, MAREK-MARSEL M (contact);ROGALSKI, EMILY J

PROGRAM_OFFICER_NAME: SUTTERER, MATTHEW

PROJECT_TERMS: Address;Affect;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease related dementia;Anatomy;Architecture;Autopsy;Award;Brain;brain dysfunction;brain tissue;Cerebral hemisphere;Characteristics;Clinical;clinical subtypes;Cognitive;cohort;Communication;Dedications;Dementia;Development;Disease;Enrollment;Episodic memory;Evaluation;experience;Family;Fingerprint;Foundations;Frontotemporal Lobar Degenerations;Gene Expression;Genetic;genetic analysis;genome analysis;Goals;graph theory;Heterogeneity;human subject;Image;imaging approach;Individual;Individual Differences;inflammatory marker;innovation;Knowledge;Language;Lead;Left;Magnetic Resonance Imaging;Maps;Mediating;Memory;Molecular;molecular pathology;Molecular Profiling;Multimodal Imaging;National Institute on Deafness and Other Communication Disorders;National Research Service Awards;Nerve Degeneration;network architecture;Neurobiology;Neurodegenerative Disorders;Neurofibrillary Tangles;neuropathology;Participant;participant enrollment;Patients;Pattern;personalized medicine;Phenotype;Predisposition;preservation;Primary Progressive Aphasia;programs;Progressive Aphasias;prospective;Registries;repository;Research;Research Methodology;Research Project Grants;resilience;Resources;Route;Scientist;Speech Therapy;Structure;Symptoms;Syndrome;Therapeutic;Thinness;tissue resource;Tissues;Training;Tropism;Variant;Visit;whole genome;Work

PROJECT_TITLE: ASYMMETRIC NEURODEGENERATION AND LANGUAGE IN PRIMARY PROGRESSIVE APHASIA


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Kidney Disease

ORG_CITY: BOSTON

ORG_NAME: BOSTON MEDICAL CENTER

ORG_STATE: MA

PHR: Project Narrative Ischemic acute kidney injury (AKI) is a common and often a life-threatening consequence of reduced kidney blood flow during cardiac surgery caused by NPM, a key protein that promotes regulated cell death and tissue injury in the human kidney. We will use an integrated approach to characterize the structure-function relationship (SAR) of human NPM and Bax to identify novel targets for drug interventions with non-toxic, injectable peptides. Our goal is to prevent and treat regulated cell death that causes AKI during cardiac surgery, an insult that resembles experimental ischemia-reperfusion injury in which NPM and Bax are lethal co- toxins.

PI_NAMEs: BORKAN, STEVEN C. (contact)

PROGRAM_OFFICER_NAME: SCHULMAN, IVONNE HERNANDEZ

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Address;ADME Study;Amino Acid Sequence;Amino Acids;Animals;Bilateral;Binding;Biological Assay;Blood flow;Brain;Cardiac Surgery procedures;Cause of Death;Cell Death;Cells;Cellular biology;Clinic;Clinical;Complex;Consensus;Coupled;crosslink;Crystallography;delayed graft function;design;Development;Diagnostic;Drug Design;Drug Kinetics;Drug Stability;Drug Targeting;drug testing;Epithelial Cells;Escherichia coli;Event;Exposure to;Financial cost;Generations;Goals;Heart;high risk;Histologic;Human;improved;In Vitro;in vivo;Inflammation;inhibitor;Injectable;Injury;Intervention;Ischemia;ischemic injury;Isotopes;Kidney;kidney cell;Kidney Failure;kidney preservation;Kidney Transplantation;Length;Life;Ligand Binding;Liver;Mass Spectrum Analysis;Measures;Mediating;Medicine;Metabolic;Mitochondria;Molecular Chaperones;Molecular Target;monomer;mortality;Mus;new therapeutic target;novel;novel therapeutics;NPM1 gene;Nuclear;nucleophosmin;Patients;peptide drug;Peptides;Pharmaceutical Chemistry;Pharmaceutical Preparations;Phosphorylation;Photoaffinity Labels;Plasma;post gamma-globulins;pre-clinical;preclinical study;predictive modeling;Predisposition;prevent;Property;protein protein interaction;Proteins;prototype;Public Health;Regulation;Renal function;renal ischemia;Reperfusion Injury;Role;Sepsis;Serum;Severities;Site;standard of care;Stress;structural biology;Structural Chemistry;Structure;Structure-Activity Relationship;Techniques;Testing;Therapeutic;therapeutically effective;tissue injury;Tissues;Toxic effect;Toxin;Translating;Uncertainty;urinary tract obstruction;Urine;Validation;virtual;X-Ray Crystallography

PROJECT_TITLE: Nucleophosmin Centered Diagnostics and Treatment of Ischemic Acute Kidney Injury

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


FUNDING_MECHANISM: RESEARCH CENTERS

NIH_SPENDING_CATS: Diabetes;Nutrition

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PI_NAMEs: ZELTSER, LORI M (contact)

PROJECT_TERMS: 3-Dimensional;analytical tool;Antibodies;base;Biological Assay;blood glucose regulation;bone;Brain;Cell surface;Cells;cellular pathology;Complement;Computer software;Confocal Microscopy;Consultations;cost;cost effective;cryostat;Cryoultramicrotomy;Custom;Data;Diabetes Mellitus;Diabetic mouse;Effectiveness;Electrons;Elements;energy balance;Equipment;equipment acquisition;Equity;Experimental Designs;Fatty acid glycerol esters;Formalin;Frozen Sections;Funding;Genetic;Heart;Hematopoietic System;Histologic;histological stains;Histology;Histopathology;human tissue;Image;image processing;Imaging technology;Immunologics;improved;In Situ Hybridization;Individual;induced pluripotent stem cell;instrumentation;Investments;Label;Light;live cell imaging;Liver;Maintenance;Mediation;member;Metabolic;Metabolic Diseases;metabolic phenotype;Methods;Microscope;Microscopy;Mission;Molecular;Monitor;Mus;Muscle;Nature;new technology;Oils;Organ;Organoids;Pancreas;Paraffin;Pathogenesis;Pathology;Peripheral;Phenotype;Procedures;Productivity;Protocols documentation;Quality Control;Reagent;Recommendation;Reproducibility;Research;Research Personnel;Resources;response;Running;sample fixation;Sampling;Services;single molecule;Stains;Surveys;System;Technical Expertise;Techniques;Tissue Fixation;tissue processing;Tissue Sample;Tissues;Training;two-photon;ultra high resolution;Universities;Visualization

PROJECT_TITLE: Advanced Tissue Pathology and Imaging


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Clinical Research;Congenital Structural Anomalies;Genetics;Networking and Information Technology R&D (NITRD);Pediatric

ORG_CITY: SAN ANTONIO

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: Project Narrative The goal of this project is to enhance the value to the research community of the structural birth defect data on the Kids First cohort with chromosome 18 deletions. We propose to review and abstract the existing repository of scanned medical records and survey data and recontact the participating families to acquire any additional or more recent information. These data will then be mapped to Human Phenotype Ontology to ensure harmonization with the larger database. The added precision, detail and interoperability of these data will help advance the discovery of the genetic causes of these structural birth defects.

PI_NAMEs: CODY, JANNINE DE MARS (contact)

PROGRAM_OFFICER_NAME: STEIN, KATHRYN K

PROJECT_TERMS: Address;cancer diagnosis;Categories;Child;Chromosome 18;Chromosome Deletion;clinical research site;cohort;Communities;Complement;Congenital Abnormality;Data;Data Element;data exchange;data harmonization;data integration;data interoperability;data resource;Data Set;data sharing;data submission;Databases;disease classification;endophenotype;Ensure;Evaluation;Family;Feedback;follow-up;Genes;Genetic;genomic data;Goals;Human;Individual;Inherited;interoperability;Knowledge;Malignant Neoplasms;Maps;Medical;Medical Records;Molecular;Monitor;Mutation;Natural History;Ontology;Other Genetics;Outcome;Parents;Participant;Pediatric Hospitals;Pediatric Research;Penetrance;Periodicals;Persons;Pharmaceutical Preparations;Phenotype;phenotypic data;Philadelphia;programs;Questionnaires;Recontacts;Recording of previous events;Records;Reporting;repository;Research;research clinical testing;Research Personnel;Scanning;Site;Source;Standardization;Structural Congenital Anomalies;Surveys;System;Terminology;Treatment outcome;Update;Work

PROJECT_TITLE: Chromosome 18 Cohort Phenotype Enrichment to Strengthen the Gabriella Miller Kids First Program


ADMINISTERING_IC: DP

IC_NAME: NATIONAL CENTER FOR CHRONIC DISEASE PREVENTION AND HEALTH PROMOTION

ORG_CITY: HONOLULU

ORG_NAME: HAWAII STATE DEPARTMENT OF HEALTH

ORG_STATE: HI

PHR: 2021-2026 PRAMS Application Identifier: 801548 Hawaii (July 2020) Hawaii PRAMS Project Narrative  The mission of the Hawaii State Department of Health is to protect and improve the health and environment for all people in Hawaii .The Hawaii Pregnancy Risk Assessment Monitoring System (PRAMS) Program fulfills this mission through collecting and analyzing both quantitative and qualitative data on maternal behaviors before, during, and immediately after pregnancy. The information from Hawaii PRAMS is invaluable to providers, policy makers, and program managers who use it to design prevention, treatment, and education programs and policies to increase the health of women and infants in Hawaii.

PI_NAMEs: SHIM, MATTHEW J (contact)

PROJECT_TITLE: DP21-001 Hawaii Pregnancy Risk Assessment Monitoring System (PRAMS)


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

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

ORG_CITY: IOWA CITY

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative: The proposed project evaluates the effectiveness of the National Background Check Program in lowering resident abuse, neglect, and exploitation and improving patient safety outcomes in nursing homes. It is relevant to public health because it will provide empirical evidence for state and national policymakers on whether National Background Check Program has had the intended effect of improving nursing home quality for a vulnerable population.

PI_NAMEs: SHARMA, HARI  (contact)

PROGRAM_OFFICER_NAME: KELLER, CHANDRA

PROJECT_TERMS: abuse neglect;adverse outcome;Affect;Affordable Care Act;Age;Alzheimer's Disease;Alzheimer's disease related dementia;Antipsychotic Agents;care providers;Caregivers;Censuses;Cessation of life;cognitive function;Communication;convict;cost;Coupled;Data;decubitus ulcer;Dehydration;Dementia;design;econometrics;Effectiveness;effectiveness evaluation;Elder Abuse;elder neglect;Elderly;Employee;Employment;Evaluation;experience;Face;Failure;falls;financial exploitation;Fingerprint;Fracture;functional status;Funding;Goals;Grant;Healthcare;Heterogeneity;human old age (65+);Impaired cognition;improved;improved outcome;Incidence;Individual;Infection;Injury;Investments;Knowledge;Life;Link;Long-Term Care;Malnutrition;maltreatment;Mental Depression;mortality;neglect;Nursing Homes;Occupations;Older Population;Outcome;Pain;patient safety;Patients;perpetrators;Personal Satisfaction;Persons;physical abuse;Physical Function;Policies;Policy Maker;Population;Predisposition;programs;prospective;psychologic;Public Health;Quality of Care;Quality of life;Quasi-experiment;Recording of previous events;Records;Registries;Reporting;Research Personnel;Resource Allocation;Resources;safety outcomes;Savings;Services;sexual assault;Statutes and Laws;Stress;Surveys;treatment effect;Variant;Voluntary Programs;Vulnerable Populations

PROJECT_TITLE: Improving Quality of Care for Persons with Dementia in Nursing Homes – Evaluation of the National Background Check Program

STUDY_SECTION: ODHS

STUDY_SECTION_NAME: Organization and Delivery of Health Services Study Section[ODHS]


ORG_CITY: SAN JUAN

ORG_NAME: PUERTO RICO DEPARTMENT OF HEALTH

ORG_STATE: PR

PHR: Puerto Rico Pregnancy Risk Assessment Monitoring System: Core Component A Project Narrative The accurate and continuous data obtained from PR-PRAMS will fill in information gaps. The data gathered on the morbidity of women before and during pregnancy is important to ascertain the factors influencing positive and/or adverse pregnancy outcomes. This will allow for informed decision making, resource allocation, policies, and systems changes that support effective programming of services for women and infants, resulting in public health impact and improvements in population health.

PI_NAMEs: VARGAS, MANUEL I. (contact)

PROJECT_TITLE: RFA-DP-21-001 DP006602 PUERTO RICO PREGNANCY RISK ASSESSMENT MONITORING SYSTEM COMPONENT A: CORE SURVEILLANCE


NIH_SPENDING_CATS: Clinical Research;Diabetes

PI_NAMEs: LEIBEL, RUDOLPH L (contact)

PROJECT_TERMS: Advertising;Applications Grants;Area;Award;career;Communities;Data;Diabetes Mellitus;Direct Costs;Disease remission;effectiveness measure;Ensure;experience;Extramural Activities;Faculty;Foundations;frontier;Funding;Grant;Individual;Industry;Institution;interest;Leadership;Letters;medical schools;Metabolism;Monitor;New York;Obesity;Outcome;Peer Review;Postdoctoral Fellow;Productivity;Program Effectiveness;Program Reviews;programs;Recommendation;Records;Reporting;Research;Research Personnel;Research Project Grants;Research Support;Resources;retention rate;Scientist;Talents;technology development;Underrepresented Minority;United States National Institutes of Health;Universities;Woman;Work

PROJECT_TITLE: Pilot and Feasibility Program


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

ORG_STATE: WA

PHR: PROJECT NARRATIVE: Sarah Leary is an extremely qualified and experienced Clinical Scientist whose goal is to improve survival for children with brain tumors. This award would support her work nationally to maximize the impact of the NCI- COG partnership to bring molecular characterization to children with CNS tumors; to develop the next generation of COG trials for children relying on centralized molecular risk stratification; and to support clinical and genomic data sharing efforts. Local institutional goals are to strengthen Seattle Children’s/Fred Hutchinson/UW cancer consortium clinical research operations infrastructure to decrease time to pediatric clinical trial implementation and increase equitable access and enrollment in clinical trials.

PI_NAMEs: LEARY, SARAH ELISABETH SHERR (contact)

PROGRAM_OFFICER_NAME: TAWAB-AMIRI, ABDUL

PROJECT_TERMS: Acceleration;anti-cancer research;Award;Biological;Brain;Brain Neoplasms;Cancer Etiology;Central Nervous System;Central Nervous System Neoplasms;Child;Childhood;Childhood Brain Neoplasm;childhood cancer mortality;Clinical;Clinical Data;Clinical Research;clinical trial implementation;Clinical Trials;Clinical Trials Network;Data;data sharing;Development;Disease;early phase clinical trial;Enrollment;Equity;experience;Funding;genomic data;Goals;improved;Infrastructure;insight;Institution;International;Leadership;Malignant Childhood Neoplasm;Malignant Neoplasms;Molecular;molecular diagnostics;Morbidity - disease rate;National Clinical Trials Network;next generation;novel therapeutics;Operations Research;Pediatric Hospitals;Pediatric Oncology Group;Phase;Physician Executives;Principal Investigator;programs;Qualifying;Registries;Research;risk stratification;Role;Scientist;Site;targeted treatment;Time;Translating;Translational Research;Treatment-related toxicity;Tumor Bank;Tumor Biology;United States National Institutes of Health;Work

PROJECT_TITLE: Pediatric brain tumors: Improving survival through integration of clinical molecular diagnostics and biologically targeted therapies into clinical trials


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

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

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: NEW YORK UNIVERSITY

PHR: Project Narrative  Signaling molecules, such as serotonin (5-HT), which do not cross cell membranes, must activate receptors on cell surfaces to which receptors are transported from their intracellular site of biosynthesis. Evidence suggests that insertion of the 5-HT4 receptor subtype into cell surface membranes in the brain is critically dependent on an interaction with another molecule, p11, which functions as an adaptor. We plan to test three hypotheses strongly supported by our preliminary data, (i) that the p11-5-HT4 interaction is necessary for insertion of 5-HT4 receptors into cell surface membranes of intestinal nerve and epithelial cells, is thus (ii) essential for 5- HT4-stimulation of enteric neuronal development and function, and, (iii) when defective, underlies the frequent co-existence of 5-HT4-mediated brain and gut disorders, including constipation and depression.

PI_NAMEs: MARGOLIS, KARA GROSS (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: 5-hydroxy-tryptophan;Affect;affective disturbance;Age Months;Agonist;Anabolism;analog;antinociception;Anxiety;Biotinylation;Brain;brain dysfunction;Bypass;Cell membrane;Cell surface;Central Nervous System;Clinical;Co-Immunoprecipitations;comorbidity;Comprehension;Constipation;cost;Curiosities;Data;Defect;depression model;depressive behavior;depressive symptoms;design;Development;Disease;Economic Burden;Educational workshop;effective therapy;Enteral;Enteric Nervous System;Environmental Exposure;Enzymes;Epithelial Cells;Epithelium;Exhibits;Failure;Functional disorder;Functional Gastrointestinal Disorders;gastrointestinal;gastrointestinal function;Gastrointestinal Motility;Gastrointestinal tract structure;Genetic;Genetic Transcription;genetic variant;High Prevalence;Human;Immunofluorescence Immunologic;Impairment;improved;in vivo;Individual;Intestinal Mucosa;Intestines;Irritable Bowel Syndrome;Knowledge;Lead;Lesion;Life;Maintenance;Mediating;Membrane;Mental Depression;Molecular;Mood Disorders;Moods;motility disorder;mouse model;Mucous Membrane;Mus;nervous system development;neurogenesis;neuron development;Neurons;novel;novel therapeutics;Pathogenesis;Patients;Phenotype;Play;pre-clinical;Prevalence;psychiatric comorbidity;Quality of life;receptor;Role;Serotonergic System;Serotonin;Serotonin Receptors 5-HT4;Signal Transduction;Signaling Molecule;Site;Suggestion;suicide victim;Symptoms;Testing;TPH2;trafficking;Transgenic Mice;Treatment Failure;United States National Institutes of Health;Variant

PROJECT_TITLE: Linkage of s100a10 (p11) to enteric 5-HT4-mediated serotonergic signaling roles in GI motility, enteric nervous system development, and co-morbid dysfunction of gut and brain

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-A(90)]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Cannabidiol Research;Cannabinoid Research;Clinical Research;Clinical Trials and Supportive Activities;Harm Reduction for Substance Misuse;Natural Products;Prevention;Substance Misuse;Therapeutic Cannabinoid Research

ORG_CITY: Aurora

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Research Narrative  As access to cannabis has increased dramatically, it is imperative to understand how to approach cannabis use among individuals with alcohol use disorder (AUD) who also use cannabis. The proposed research will compare the effects of a harm reduction intervention (instruction to switch from a high THC product to a low THC/high CBD) product versus a no intervention control condition (continue to use THC like you normally do) in a sample of cannabis users who wish to reduce or quit drinking. If the hypotheses of the proposed research are supported, the dissemination of the research would have an immediate public health impact by educating individuals and health care providers about the relative benefits of switching from high potency THC products to a product with lower THC and higher CBD.

PI_NAMEs: HUTCHISON, KENT E. (contact)

PROGRAM_OFFICER_NAME: FALK, DANIEL EVAN

PROJECT_TERMS: Address;Alcohol consumption;alcohol craving;alcohol use disorder;Alcohols;Antiinflammatory Effect;Anxiety;Biological Markers;Canada;Cannabidiol;Cannabinoids;Cannabis;comorbidity;Consumption;craving;Cues;Data;Disease;District of Columbia;drinking;Drug usage;economic cost;Grant;Harm Reduction;Health Personnel;Hemp;improved;Individual;Inflammation;Inflammatory;Instruction;Intervention;intervention effect;Intoxication;Laboratories;Legal;Literature;marijuana legalization;marijuana use;marijuana use disorder;marijuana user;Mediating;Medical Marijuana;men;Mexico;North America;novel;Outcome;Participant;Patients;Persons;Pharmaceutical Preparations;Pharmacology;Population;Prevalence;Public Health;Publishing;Randomized;Research;Research Support;Sales;Sampling;socioeconomics;Symptoms;systemic inflammatory response;Testing;treatment program;trend;United States;Woman;women versus men;Work

PROJECT_TITLE: Alcohol Use Disorder and Cannabis: Testing Novel Harm Reduction Strategies

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE (PUBLIC HEALTH RELEVANCE) Patients with systemic lupus erythematosus (SLE, lupus) commonly have injury to their kidneys, called lupus nephritis. We and others have found that lymphocytes enter the kidney in lupus nephritis, and promote the injury that occurs therein. We now propose to determine the factors that contribute to the damage caused by kidney lymphocytes in mice and humans with lupus, and how we can modify them genetically and therapeutically to potentially prevent lupus nephritis, studies that could lead to new treatments for SLE.

PI_NAMEs: CRAFT, JOSEPH EDGAR (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Address;Affect;Antigen-Antibody Complex;Autoantibodies;Automobile Driving;autoreactive B cell;autoreactive T cell;B-Cell Activation;B-Lymphocytes;Blood Cells;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Maturation;Cell Physiology;Cell Survival;Cells;Cellular Metabolic Process;Characteristics;Chromatin;Data;Deposition;effector T cell;Ensure;Environment;environmental adaptation;Environmental Risk Factor;Epigenetic Process;epigenome;Event;Genetic;genetic manipulation;Genetic Transcription;Goals;Human;Hypoxia;hypoxia inducible factor 1;Immune;immune cell infiltrate;Immune Complex Glomerulonephritis;immunoregulation;In Situ;In Vitro;in vivo;Infiltration;Inflammation;Inflammatory;inflammatory milieu;Inflammatory Response;Injury;Injury to Kidney;Interruption;Kidney;kidney biopsy;Knowledge;Lupus;Lupus Nephritis;Lymphocyte;Metabolic;Microscopic;Modeling;Modification;Morbidity - disease rate;mortality;Mus;novel;organ injury;Outcome;Oxygen;pathogen;Pathogenesis;pathogenic autoantibodies;Pathogenicity;Pathway interactions;Patients;peripheral blood;pharmacologic;phase I trial;Phenotype;Physiological;prevent;Production;programmed cell death protein 1;public health relevance;Regulation;renal damage;renal hypoxia;response;secondary lymphoid organ;Severity of illness;Shapes;Site;Spleen;Stress;Systemic Lupus Erythematosus;T cell infiltration;T-Cell Activation;T-Lymphocyte;Therapeutic;Therapeutic Agents;therapeutic target;tissue injury;Tissues;transcription factor;tumor;Work

PROJECT_TITLE: Pathogenesis of Lupus Nephritis

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


ADMINISTERING_IC: HL

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Clinical Research

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE Excess adrenal steroid production is increasingly recognized as a common cause of hypertension and cardiovascular disease, with medical therapies that remain suboptimal and biological mechanisms that remain incompletely defined. We have developed novel methods for deeply interrogating the proteome and bioenergetics of adrenal mitochondria and have obtained preliminary data for several redox pathways that are uniquely enriched in adrenal mitochondria. The proposed research will test the concept that dysfunction of adrenal mitochondrial redox pathways can be a pathogenic driver of dysregulated aldosterone and cortisol production relevant for common hypertension and cardiovascular disease.

PI_NAMEs: WARD, PATRICK S. (contact)

PROGRAM_OFFICER_NAME: LIDMAN, KARIN FREDRIKSSON

PROJECT_TERMS: Address;Adrenal Glands;Aldosterone;Area;Bioenergetics;Biological;Biological Assay;Biology;Buffers;Cardiovascular Diseases;Cardiovascular system;career;Cells;Citric Acid Cycle;Clinical;clinical training;Clustered Regularly Interspaced Short Palindromic Repeats;cofactor;Coupled;Custom;Data;Diagnosis;DNA Sequence Alteration;Doctor of Philosophy;Electron Transport;Endocrinology;Environment;Enzymes;Etiology;Exhibits;Functional disorder;Funding;General Hospitals;Goals;Human;Human Genetics;Hydrocortisone;Hypertension;hypertension treatment;Impairment;inhibitor;Institution;instructor;Internal Medicine;Knowledge;Label;Laboratories;loss of function mutation;Massachusetts;Measurement;Medical;Mentors;Mentorship;Metabolic;Metabolism;Methodology;Methods;Mitochondria;Mitochondrial Proteins;Modeling;NAD(P)+ transhydrogenase;NADH;NADP;novel;NQO1 gene;Output;Oxidation-Reduction;Oxidative Stress;Oxidoreductase;Pathogenicity;Pathway interactions;Permeability;Physiological;Physiology;Positioning Attribute;Preparation;Production;programs;Proteome;Proteomics;Quinones;Recombinants;Regulation;Research;Resources;Role;Shunt Device;Source;stable isotope;Steroid biosynthesis;Steroids;Stimulus;System;Testing;Tissues;tool;Training;tumor metabolism;uptake;ward

PROJECT_TITLE: Mitochondrial redox regulation of adrenal steroidogenesis

STUDY_SECTION: MCBS

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROSCIENCES

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Although most G-protein coupled receptors are activated by contact with their neurotransmitters at the cell surface, new data suggest that some receptors, such as the metabotropic glutamate mGlu5 receptor, are primarily expressed on intracellular membranes where they trigger distinct and longer lasting signaling responses. Recently, we created genetic models to test membrane-restricted mGlu5 signaling in motivated learning and memory assays in vivo. Because mGlu5 has been linked to disorders of intellectual disability, anxiety, and depression, these studies have enormous potential for the discovery of novel therapies that improve outcomes for people with these disorders.

PI_NAMEs: O'MALLEY, KAREN L (contact)

PROGRAM_OFFICER_NAME: NADLER, LAURIE SUE

PROJECT_TERMS: Acoustics;Agonist;Animal Behavior;Animal Disease Models;Animal Model;Animals;antagonist;Anxiety;anxiety-like behavior;autism spectrum disorder;Behavior;Behavioral;Biological Assay;Biological Models;Biology;Brain;Cancer Therapy Evaluation Program;Candidate Disease Gene;cell behavior;Cell surface;Cells;chronic pain;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Corpus striatum structure;cost;Couples;Data;depressive symptoms;Development;Disease;disease model;Drug Targeting;Economics;Exhibits;expectation;experimental study;Frequencies;Future;G-Protein-Coupled Receptors;genetic approach;Genetic Models;Glutamate Transporter;Glutamates;Goals;GRM5 gene;Human;human disease;improved;improved outcome;In Vitro;in vivo;insight;Intellectual functioning disability;Intracellular Membranes;Knowledge;Learning;Link;Location;Long-Term Depression;MAPK3 gene;Mediating;Medical;Membrane;Memory;Mental Depression;metabotropic glutamate receptor 5;Metabotropic Glutamate Receptors;Modeling;Motor;Mus;Neurons;neuropsychiatric disorder;Neurotransmitters;new therapeutic target;novel therapeutics;Outcome;pain behavior;Pathway interactions;Persons;Pharmaceutical Preparations;pharmacologic;Phenocopy;Phenotype;Phosphorylation;Physiological;Play;Preparation;Process;quisqualate;receptor;Receptor Signaling;receptor-mediated signaling;Regulation;Reporting;Research;response;Rewards;Role;Signal Pathway;Signal Transduction;Slice;social;success;Swimming;Synapses;Synaptic plasticity;System;Testing;Therapeutic;therapeutic target;Time;tool;transcriptome;transcriptome sequencing;transcriptomic profiling;Up-Regulation;Variant;Western Blotting;Work

PROJECT_TITLE: Testing the role of intracellular vs. cell surface mGlu5 in models of synaptic plasticity using CRISPR-modified mice

STUDY_SECTION: MNPS

STUDY_SECTION_NAME: Molecular Neuropharmacology and Signaling Study Section[MNPS]


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

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Each year nearly 2 million individuals become infected with HIV-1 and with no universal cure, development of an effective vaccine to prevent HIV-1 infection remains a major goal. A significant hurdle for the development of a successful vaccination strategies has been the lack of tractable and affordable preclinical model system. This application will leverage the combined expertise of three PIs (Drs. Goettel, Almodovar, and Georgiev) to employ a newly developed advanced immune humanized murine system to evaluate the antibody response to HIV-1 (R5) virus infection as well as vaccination protocols using established and novel HIV-1 immunization approaches.

PI_NAMEs: GOETTEL, JEREMY ALLEN (contact)

PROGRAM_OFFICER_NAME: VIJH, SUJATA

PROJECT_TERMS: Acceleration;activation-induced cytidine deaminase;adaptive immune response;adaptive immunity;Animal Model;Antibodies;Antibody Formation;Antibody Response;Antigen-Presenting Cells;antigen-specific T cells;Antigens;antiretroviral therapy;Autologous;B-Cell Antigen Receptor;B-Lymphocytes;Basic Science;Binding Sites;Biological Models;CD34 gene;Cell Communication;Cell Physiology;Cell Separation;clinical application;Clinical Trials;Complex;CSF1 gene;Data;Development;Disease;Engraftment;Ensure;Epitopes;Ethics;Evaluation;Exhibits;fetal;Future;Generations;Genes;Goals;graft vs host disease;Hematopoiesis;Hematopoietic stem cells;Histocompatibility Antigens Class I;HIV;HIV Infections;HIV-1;HLA Antigens;Human;human fetus tissue;humanized mouse;Immune;Immune response;Immune system;Immunization;Immunodeficient Mouse;Immunophenotyping;Implant;improved;Individual;Infection;insight;interest;Investigation;life span;Liver;Lymphocyte;Lymphoid Cell;Major Histocompatibility Complex;Mediating;Methods;mouse model;Mouse Strains;Mus;Myelogenous;Myeloid Cells;Myelopoiesis;nanoparticle;Natural Killer Cells;neutralizing antibody;next generation;nonhuman primate;novel;Operative Surgical Procedures;Pathogenesis;Penetration;Polysaccharides;pre-clinical;Pre-Clinical Model;prevent;Prevention;Protocols documentation;Publishing;receptor binding;reconstitution;Research Personnel;response;Somatic Mutation;Source;System;T-Cell Activation;T-Cell Depletion;T-Cell Development;T-Lymphocyte;Techniques;Testing;Thymus Gland;Tissues;Translating;Translational Research;translational study;transmission process;Tropism;Umbilical Cord Blood;universal vaccine;Vaccinated;Vaccination;vaccination protocol;vaccination strategy;vaccine trial;Vaccines;Virus;Virus Diseases;Virus Replication;Work;Xenograft procedure

PROJECT_TITLE: Characterizing antibody responses to HIV-1 vaccination in next-generation immune humanized mice

STUDY_SECTION: HIVD

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


NIH_SPENDING_CATS: Microbiome

ORG_CITY: ATLANTA

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Narrative The goal of this project is to develop novel statistical methods for analyzing microbiome data that allow testing of various hypotheses with a wide range of datasets, while accounting for all data complexities. These methods, implemented in a user-friendly software package, will accelerate analysis of rapidly accumulating microbiome data and thus expedite our understanding of the roles that the microbiome play in human health and diseases.

PI_NAMEs: SU, CHANG  (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Acceleration;Address;Advocate;Alzheimer's Disease;Basic Science;Benchmarking;Biological;Biological Markers;Clinical;Clinical Research;Collaborations;Complex;cost;Data;data complexity;Data Set;Disease;disease diagnosis;Disease Outcome;disease prognosis;Equation;Failure;flexibility;Genes;Goals;Health;high dimensionality;Human;Human Microbiome;improved;Individual;Inflammatory Bowel Diseases;interest;Intervention;longitudinal analysis;Longitudinal Studies;Malignant Neoplasms;Mediating;Mediation;Metagenomics;Methodology;Methods;Microbe;microbial community;microbiome;microbiome analysis;microbiome research;Modeling;multiple datasets;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;operational taxonomic units;Outcome;Paper;Play;Procedures;programs;Reproducibility;Research Personnel;Risk;Role;rRNA Genes;Running;Sample Size;Sampling;semiparametric;Shotguns;simulation;Statistical Methods;Testing;trait;Universities;user friendly software;Work

PROJECT_TITLE: Novel Statistical Methods for Analyzing Complex Microbiome Data

STUDY_SECTION: BMRD

STUDY_SECTION_NAME: Biostatistical Methods and Research Design Study Section[BMRD]


NIH_SPENDING_CATS: Behavioral and Social Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Nutrition;Social Determinants of Health

ORG_CITY: Chicago

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: NORTHWESTERN UNIVERSITY

PHR: PROJECT NARRATIVE Although the global water crisis is among the most urgent issues of our time, little attention has been given to the myriad ways in which problems with water access, use, and stability (i.e., water insecurity) can influence health beyond waterborne diseases; this R03 therefore examines the underexplored relationships between water insecurity and nutritional, physiological, and mental health. Household water insecurity experiences were measured in a nationally representative health and nutrition survey for the first time in 2021 (Mexico's renowned Encuesta Nacional de Salud y Nutrición); these data will permit the quantification of the role of water insecurity and food insecurity in key health outcomes, including dietary intake, adiposity, hypertension, diabetes, and depression. The proposed work will demonstrate the utility of the measurement of water insecurity in other large surveys (including in the US) and identify previously unrecognized but modifiable drivers of health inequities, thereby helping public health efforts to address root causes of poor mental and physical health that hinder resilience, economic growth, and well-being.

PI_NAMEs: YOUNG, SERA LEWISE (contact)

PROGRAM_OFFICER_NAME: CAMPBELL-ROSEN, HOLLY RENEE

PROJECT_TERMS: Address;Adult;antiretroviral therapy;Area;Attention;Blood Pressure;Characteristics;Child;climate change;Communities;Country;Data;depressive symptoms;Diabetes Mellitus;dietary;Dietary intake;Distal;Economics;Epidemiology;experience;feeding;Floods;Food;food insecurity;Frequencies;Fruit;Growth;Health;health inequalities;Health Surveys;Heterogeneity;HIV;Household;Human;Hydration status;Hypertension;improved;Income;Individual;Inequity;Infant;Infrastructure;innovation;insight;Intake;Intervention;Knowledge;Learning;low and middle-income countries;Measurement;Measures;Mediation;Mental Depression;Mental Health;Mexican;Mexico;Modeling;National Health and Nutrition Examination Survey;North America;novel;nutrition;Nutrition Surveys;Nutritional;Obesity;Outcome;Pathway interactions;Personal Satisfaction;physical conditioning;Physiological;poor health outcome;Population;Population Growth;Process;psychosocial stressors;Public Health;resilience;Resolution;Resources;Risk;Role;Sampling;Security;Severities;Shapes;Ships;Site;Socioeconomic Status;Statistical Models;sugar;Surveys;sweetened beverage;symptomatology;synergism;Testing;therapy adherence;Time;Vegetables;Vulnerable Populations;Water;water quality;waterborne illness;Work

PROJECT_TITLE: Understanding the synergistic roles of water insecurity and food insecurity in the health of Mexican adults

STUDY_SECTION: SSPA

STUDY_SECTION_NAME: Social Sciences and Population Studies A Study Section[SSPA]


NIH_SPENDING_CATS: Aging;Biomedical Imaging;Cancer;Estrogen;Prostate Cancer;Urologic Diseases

ORG_DEPT: UROLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: PUBLIC HEALTH RELEVANCE During the aging process nearly all men experience LUTS due to BPH. The proposed research addresses an unmet need in the urological field by performing mechanistic and preclinical studies that underpin estrogen mediated molecular and hormone pathways in BPH/LUTS.

PI_NAMEs: RICKE, WILLIAM A (contact)

PROGRAM_OFFICER_NAME: RANKIN, TRACY L

PROJECT_TERMS: 5 Alpha-Reductase Inhibitor;Address;Adrenergic alpha-Antagonists;Affect;aged;Aging;aging process;Anatomy;Benign Prostatic Hypertrophy;Binding;Biological;Bladder;Caring;cell type;Cells;Clinical;Clinical Treatment;clinically relevant;Collaborations;Collagen;Communities;cost;CRISPR/Cas technology;Data;Deposition;Development;Disease;Disease Progression;effective therapy;efficacy evaluation;Epithelial Cells;Epithelium;ESR1 gene;Estrogen Receptors;Estrogens;Etiology;Event;experience;experimental study;Extracellular Matrix;Fibrosis;Functional disorder;Future;Genes;Genetic Transcription;Goals;Health Care Costs;Healthcare;Hormone Receptor;Hormones;Human;Hyperplasia;Hypertrophy;Image;imaging modality;imaging probe;improved;In Vitro;in vivo;innovation;Kidney Diseases;Lead;Ligand Binding;Link;Lower urinary tract;lower urinary tract symptoms;Magnetic Resonance Imaging;Malignant neoplasm of prostate;Maps;Mediating;Mediator;Medical;Medicine;men;Methods;Modeling;Molecular;Molecular Mechanisms of Action;Monitor;mortality risk;mouse model;Mus;new therapeutic target;Non-Invasive Detection;novel;Obstruction;Outcome;outreach;Pathway interactions;Patient Monitoring;patient population;patient stratification;Patients;permissiveness;Physiological;Pre-Clinical Model;preclinical study;Prevention;Process;Prostate;Prostatic;Prostatic hypertrophy;Protocols documentation;public health relevance;Publishing;Quality of life;Receptor Signaling;Regulation;Reproducibility;Research;Resources;response;Response Elements;Selective Estrogen Receptor Modulators;Signal Transduction;Smooth Muscle;Specimen;spectrograph;Stratification;Stromal Cells;targeted treatment;Techniques;Testing;Therapeutic;therapeutic target;Time;Tissues;transcription factor;Transcription Factor AP-1;Treatment Efficacy;ultrasound;Urethra;urinary;Urinary Retention;urologic

PROJECT_TITLE: Estrogen pathways in the development of prostatic fibrosis and lower urinary tract dysfunction

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-B(90)]


ORG_CITY: TAMPA

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

ORG_STATE: FL

PHR: NARRATIVE Substantial progress has been made in the treatment of cardiovascular disease, yet it remains the leading cause of death in humans. Much of this success has resulted from the development of treatments that target the underlying genetic and molecular mechanisms responsible for these devastating conditions. The studies proposed here will identify new gene targets and pathways that can also be investigated as potential avenues for therapy in patients with cardiovascular disease.

PI_NAMEs: WANG, DA-ZHI  (contact)

PROGRAM_OFFICER_NAME: POIZAT, CORALIE ISABELLE

PROJECT_TERMS: Adaptor Signaling Protein;Adherens Junction;Adult;Affect;Age;beta catenin;Binding;Biochemical;Biological Process;Cardiac;Cardiac Myocytes;cardiac regeneration;cardiogenesis;Cardiomyopathies;Cardiovascular Diseases;Cause of Death;cell growth;Cell Nucleus;Cell Proliferation;Cells;cofactor;Complex;Defect;design;Development;Disease;DNA Sequence Alteration;Elderly;Feedback;Gene Expression;Gene Targeting;Genes;Genetic;Genetic Transcription;Giant Cells;Healthcare;Heart;heart defect;Heart Diseases;heart function;Human;human disease;Impairment;Incidence;Intercalated disc;Intercellular Junctions;Knock-out;Knockout Mice;Link;Location;Maintenance;Malignant Neoplasms;Mechanics;Mediating;Molecular;Mutant Strains Mice;Myocardial Contraction;Myocardium;N-Cadherin;Natural regeneration;Neurofibromin 2;new therapeutic target;Nodal;novel;overexpression;paralogous gene;Pathogenesis;Pathway interactions;Patients;Phosphorylation;Play;Population;postnatal;Process;programs;Proliferating;Protein Kinase;Proteins;Publishing;Regulation;Regulatory Pathway;Reporting;Repression;Role;Series;Signal Transduction;Structure;Subcellular structure;success;System;targeted treatment;Testing;Therapeutic Intervention;therapy development;tissue repair;transcription regulatory network;Translations;transmission process;Work

PROJECT_TITLE: Function and Mechanism of the Intercalated Disc Protein XinB in Cardiomyocyte Proliferation and Cardiac Regeneration

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Immunotherapy;Neurosciences;Rare Diseases

ORG_CITY: STANFORD

ORG_DEPT: NEUROSURGERY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: Checkpoint inhibitor immunotherapy has improved the treatment of many solid tumors, and an active investigation to treat glioblastomas (GBM) with a dual immune checkpoint blockade strategy has thus far yielded promising signs of efficacy. Our proposal aims to study the mechanisms by which immune checkpoint blockades promote a multifaceted immune response in GBM tumor types. A thorough understanding of these mechanisms will further inform the effective design of new strategies, and improve current therapeutic strategies, for patients with GBM.

PI_NAMEs: LIM, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: Ablation;Adoptive Transfer;Adult;anti-cancer;anti-CTLA4;anti-PD-1;anti-PD1 antibodies;anti-PD1 therapy;anti-tumor immune response;Antibodies;Antigen Presentation;Antigen-Presenting Cells;Antitumor Response;Binding;Biological Assay;Blood;Blood specimen;Bone Marrow;Brain Neoplasms;cancer type;Cells;Clinical;Clone Cells;Coculture Techniques;combinatorial;Congenic Mice;Correlative Study;CTLA4 gene;cytotoxicity;Data;design;draining lymph node;effector T cell;exhaustion;extracellular;Flow Cytometry;functional improvement;Funding;Future;Glioblastoma;Glioma;Histology;Human;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;Immune response;Immune system;Immunosuppression;Immunotherapy;improved;in vivo;Infiltration;inflammatory milieu;insight;Investigation;Ions;Knockout Mice;Knowledge;Laboratories;Long-Term Survivors;Macrophage;Malignant neoplasm of brain;Malignant neoplasm of lung;Measures;Mediating;Melanoma;Metabolic;monocyte;mouse model;Mus;Mutation;Myelogenous;Myeloid Cells;Myeloid Progenitor Cells;Myeloid-derived suppressor cells;neoantigens;neoplastic cell;novel;Patients;PD-1 blockade;Peripheral;peripheral blood;Phase I Clinical Trials;phase I trial;Phenotype;pre-clinical;prevent;Prognosis;programmed cell death protein 1;Progression-Free Survivals;Proliferating;PTPRC gene;radiological imaging;recruit;Recurrence;Renal Cell Carcinoma;Resistance;response;Role;Sampling;single cell sequencing;Site;Solid Neoplasm;Sorting;standard of care;success;Surface;synergism;T cell clonality;T cell response;T-Cell Activation;T-cell receptor repertoire;T-Lymphocyte;Testing;Therapeutic;Time;Translating;tumor;Tumor Antigens;Tumor Expansion;tumor progression;tumor-immune system interactions;Wild Type Mouse

PROJECT_TITLE: Targeting Lag-3 and PD -1 in Myeloid Cells of GBM

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Immunotherapy;Liver Cancer;Liver Disease;Rare Diseases

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: PROJECT NARRATIVE     Despite  recent  advances  in  immunotherapy  that  lead  to  substantial  increase  of  cancer  patient  survival,  still  a  great portion of patients are not responsive to the treatment, underscoring the need for a deeper understanding  of how tumor cells and immune system interact with each other. In this project, the proposed doctoral research  aims to elucidate the molecular mechanisms via which cellular senescence triggers immune surveillance against  liver cancer in vivo, with the ultimate goal of identifying new strategies to pharmacologically mimic or enhance  these effects. The proposed postdoctoral research will investigate NK cell- based mechanisms of immune escape  during  extrahepatic  metastasis  of  liver  tumors  to  lung,  which  could  offer  novel  insights  into  re- activating  this  innate immunity to target this end- stage cancer.

PI_NAMEs: CHEN, HSUAN-AN  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: adaptive immunity;Address;Advanced Malignant Neoplasm;Alleles;anti-tumor immune response;Antigen Presentation;Antigen Presentation Pathway;ATAC-seq;Automobile Driving;Biological Phenomena;Biology;Bypass;cancer cell;Cancer Control;Cancer Etiology;Cancer Patient;cancer therapy;Cell Aging;Cell Communication;Cell Cycle Arrest;cell injury;Cell surface;Cell Surface Proteins;Cells;Characteristics;Cues;Data;Development;Disease;Disease Outbreaks;dynamical evolution;Engineering;Environment;Epigenetic Process;Epithelium;Evolution;exhaustion;Extrahepatic;Genetic;Genetic Screening;Goals;Heterogeneity;Immune;immune clearance;Immune Evasion;Immune system;Immunity;Immunocompetent;Immunocompromised Host;Immunodeficient Mouse;Immunologic Surveillance;Immunology;immunoregulation;immunosenescence;Immunotherapy;Impairment;in vivo;insight;Knock-in Mouse;Label;Laboratories;Lesion;Ligands;Link;Liver neoplasms;Lung;Malignant Epithelial Cell;Malignant neoplasm of liver;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Metastatic Neoplasm to the Liver;Metastatic Neoplasm to the Lung;Modeling;Molecular;molecular dynamics;mortality;mouse model;Mouse Strains;Mus;Natural Immunity;Natural Killer Cells;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;Pathway interactions;Patients;pharmacologic;Phase;Play;Population Heterogeneity;Postdoctoral Fellow;Predisposition;Primary carcinoma of the liver cells;Process;programs;Proliferating;Proteome;Regulatory Pathway;Research;Research Project Grants;restoration;Role;senescence;senescent cell;Shapes;Side;single-cell RNA sequencing;Site;Technology;tool;TP53 gene;transcriptome sequencing;tumor;Tumor Immunity;tumor initiation;tumor progression;Tumor Promotion;tumor-immune system interactions;tumorigenesis;Validation;Virus;Work

PROJECT_TITLE: Investigating the molecular and cellular mechanisms of virus-associated hepatocellular carcinoma


NIH_SPENDING_CATS: Genetics

ORG_CITY: OMAHA

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: PROJECT NARRATIVE DNA-Protein Crosslinks (DPCs) are toxic lesions in the genome that block all DNA metabolic processes. SPRTN protease mediates proteolysis of DPCs and prevents replication-coupled DPC-induced genome instability and Ruijs-Aalfs syndrome.

PI_NAMEs: GHOSAL, GARGI  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Alleles;Attenuated;BRCA1 gene;Bypass;cancer cell;Cell Aging;Cell Death;Cell Physiology;Cells;CHEK1 gene;chemotherapy;Chromatin;Coupled;crosslink;Cytoplasm;Data;Defect;design;Deubiquitination;DNA;DNA biosynthesis;DNA Damage;DNA Repair Gene;DNA replication fork;DNA-Binding Proteins;DNA-protein crosslink;early onset;enzyme pathway;gain of function;Genetic Epistasis;Genome;Genomic Instability;Histones;IRS4 gene;knock-down;Lead;Lesion;Maintenance;Mediating;Metabolic;Metabolism;Metalloproteases;Molecular;Monoubiquitination;mutant;Mutation;novel;novel strategies;overexpression;Pathway interactions;Patients;Peptide Hydrolases;Peptides;Play;Polymerase;premature;prevent;Primary carcinoma of the liver cells;Process;Progeria;Protease Domain;protein crosslink;Proteolysis;Publishing;recruit;Regulation;repair enzyme;repaired;Role;S phase;Signal Transduction;Site;Sumoylation Pathway;Syndrome;targeted treatment;Testing;TOP1 gene;TOP2A gene;ubiquitin isopeptidase;ubiquitin-protein ligase;Ubiquitination

PROJECT_TITLE: Regulation of SPRTN protease and SPRTN-mediated DNA-Protein Crosslink Repair

STUDY_SECTION: MGA

STUDY_SECTION_NAME: Molecular Genetics A Study Section[MGA]


NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_CITY: CHICAGO

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE Many biological processes are controlled or modulated by the membrane potential via structures called voltage sensors, which are critical in the generation and propagation of nerve and muscle impulses, playing a fundamental role in excitability. This proposal aims at the understanding of the physical bases at the molecular detail of sensing voltage and how these sensors couple their action to open the ionic channels, using a combination of state-of-the-art techniques, that correlate structure and function of voltage-sensitive sodium and potassium channels. These studies have relevance in the knowledge of the basic mechanisms of the nervous system function, in skeletal muscle and heart contraction in health and, also, in a variety of diseases such as heart arrhythmias, myotonic muscle and epilepsy.

PI_NAMEs: BEZANILLA, FRANCISCO J (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: adduct;Affect;Amino Acids;Area;Arginine;Arrhythmia;base;Bathing;Biological Process;Charge;Chemistry;Couples;Coupling;Cryoelectron Microscopy;Cysteine;Data;Data Analyses;Development;Disease;Docking;Electric Capacitance;electric field;Electrophysiology (science);Epilepsy;Evolution;Fluorescence;Fluorescent Probes;Generations;global temperature;Goals;Gold;Health;Histidine;hydrophilicity;Hydrophobicity;Impairment;Ion Channel;Knowledge;large-conductance calcium-activated potassium channels;Lasers;Lighting;Link;Measures;mechanical energy;Melanins;Membrane;Membrane Potentials;Methods;Modeling;Molecular;molecular modeling;Monitor;Motion;Muscle;Muscle Contraction;mutant;Mutation;Mutation Analysis;Myocardial Contraction;Myotonia;Nerve;Nervous System Physiology;Oocytes;Osmotic Pressure;particle;Pathologic;Play;Population;Positioning Attribute;Potassium Channel;Process;prototype;receptor;Research;Resolution;restoration;Role;Rotation;sensor;simulation;Site;Skeletal Muscle;Sodium Channel;Structure;Surface;Techniques;Temperature;temperature jump;Testing;three dimensional structure;Time;Tissues;Tryptophan;Tyrosine;voltage;voltage gated channel

PROJECT_TITLE: The Electrophysiological Studies of Voltage Gated Channels

STUDY_SECTION: BPNS

STUDY_SECTION_NAME: Biophysics of Neural Systems Study Section[BPNS]


PHR: Project Narrative The proposed research is relevant to public health as it addresses a direct link between defects in human ribosome assembly and the resulting human blood disorders. Ribosomes are the molecular machines responsible for protein synthesis in all human cells. As genetic diseases associated with ribosomal protein coding genes are linked to abnormalities in the synthesis of ribosomes, this research program will be essential to understand the molecular underpinnings of these diseases.

PI_NAMEs: KLINGE, SEBASTIAN  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Address;Biochemical;Biogenesis;Biology;Cell Nucleolus;Cell Separation;Cells;Chemicals;Code;Complex;Coupled;Coupling;Cryoelectron Microscopy;Cytoplasm;Defect;Disease;Elements;Engineering;Enzymes;Event;exosome;Genes;Genetic;Genetic Diseases;Genetic Transcription;genome editing;Goals;Growth;Hematological Disease;Human;human disease;Human Genome;innovation;insight;Laboratories;Light;Link;Location;Mass Spectrum Analysis;Messenger RNA;Metabolism;Molecular;Molecular Conformation;Molecular Machines;novel strategies;Nuclear;Nuclear Export;particle;Pathway interactions;Peptides;Physical condensation;Positioning Attribute;Process;programs;Proliferating;Protein Biosynthesis;Public Health;Quality Control;Regulation;Research;Resolution;Ribosomal Proteins;Ribosomal RNA;Ribosomes;ribosomopathy;RNA;RNA Degradation;RNA Helicase;RNA Processing;Series;structural biology;Structure;Techniques;Transact;yeast genetics;Yeasts

PROJECT_TITLE: Assembly of the eukaryotic small ribosomal subunit


ADMINISTERING_IC: DC

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Patient Safety;Physical Activity;Physical Rehabilitation;Precision Medicine;Rehabilitation;Telehealth

ORG_CITY: MISSOULA

ORG_NAME: UNIVERSITY OF MONTANA

ORG_STATE: MT

PHR: PROJECT NARRATIVE The proposed research is relevant to vestibular science and the general public because age-related vestibular hypofunction is a major contributor to poor balance, falls, and other adverse health outcomes. In this investigation we propose to: 1) assess the preliminary efficacy of a novel intervention system for improving vestibular function and dizziness in community-dwelling older adults, 2) assess the safety and feasibility of the this system, and 3) assess the acceptability and implementation potential of this system, prior to a large-scale, R01-level investigation.

PI_NAMEs: LOYD, BRIAN JAMES (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Address;Adherence;adherence rate;Adverse event;Age;age related;Aged, 80 and over;Area;Behavioral;Behavioral Sciences;Blurred vision;Cardiovascular Diseases;Caring;Clinical;Clinical Practice Guideline;Clinical Trials;cohort;Communities;comparison control;computerized;Controlled Clinical Trials;Data;design;Development;Devices;Dizziness;Dose;Effectiveness;Elderly;Eligibility Determination;Equilibrium;Exercise;exercise program;exercise regimen;experience;fall risk;falls;Feedback;Future;gaze;General Population;Head;Health;improved;indexing;Individual;innovation;instrument;Intervention;Interview;Intuition;Investigation;Link;Measurement;Measures;Methods;Monitor;Musculoskeletal Equilibrium;National Institute on Deafness and Other Communication Disorders;novel;older adult;Osteoporosis;Outcome;Participant;Patient Compliance;Patient Monitoring;Patient Recruitments;Patient Self-Report;Patients;peer;personalized care;Persons;Phase;Phase II Clinical Trials;poor health outcome;Posture;Preparation;primary outcome;Publishing;Recommendation;recruit;Rehabilitation therapy;remediation;remote monitoring;remote patient monitoring;remote sensing;Reporting;Research;Research Personnel;retention rate;routine practice;Safety;safety and feasibility;safety assessment;sarcopenia;Science;secondary outcome;sedentary lifestyle;Social isolation;social norm;Structure;Symptoms;System;Technology Assessment;telehealth;Testing;Time;Treatment Efficacy;treatment response;United States National Aeronautics and Space Administration;United States National Institutes of Health;usability;Vestibular Diseases;Vestibular function;vestibular system;vestibulo-ocular reflex;Visual Acuity;wearable sensor technology;web app;Work

PROJECT_TITLE: Making INformed Decisions in Gaze and Postural Stability (MINDGAPS): a Novel System for Improving Personalized Care and Patient Adherence in Vestibular Rehabilitation

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Liver Disease

ORG_DEPT: BIOLOGY

PHR: PROJECT NARRATIVE Cell growth triggers human cell division at the G1/S transition before DNA is replicated, but our molecular understanding of this process is poor and largely based on cell culture studies. Here, we propose to determine how cell growth, through the DNA-to-cytoplasm ratio, triggers the G1/S transition in mouse hepatocytes in vivo. Determining how cell growth triggers cell division will impact our understanding of developmental biology and cancer, where this it is misregulated.

PI_NAMEs: SKOTHEIM, JAN M (contact)

PROGRAM_OFFICER_NAME: BURGESS-BEUSSE, BONNIE L

PROJECT_TERMS: Affect;Alleles;Automobile Driving;Blood capillaries;Cell Culture Techniques;Cell Cycle;Cell Cycle Progression;Cell Cycle Proteins;Cell division;cell growth;Cell model;Cell Proliferation;Cell Size;cell type;Cells;Cellular biology;Chemicals;Complex;Coupled;Cultured Cells;Cyclin D1;Cytoplasm;Data;Dependence;Development;Developmental Biology;Diploidy;DNA;DNA biosynthesis;Erythrocytes;expectation;experimental study;G1 Phase;G1/S Transition;Gene Dosage;Gene Expression;Gene Proteins;Genetic;genetic approach;Genetic Models;Genome;Growth;Hepatectomy;Hepatocyte;Human;In Vitro;in vivo;inhibitor;insight;knock-down;Laboratories;Link;Liver;liver cell proliferation;liver function;Liver Regeneration;Macrophage;Malignant Neoplasms;Mammalian Cell;Mass Spectrum Analysis;Measures;Modeling;Molecular;Mus;Natural regeneration;overexpression;p38 Mitogen Activated Protein Kinase;pathogen;Pathologic;Pathway interactions;Phosphotransferases;Physiological;Ploidies;Process;Proliferating;Proteins;RB1 gene;regenerative;Replication Initiation;Retinoblastoma Protein;Series;Signal Transduction;Sorting;Stress;Testing;Work

PROJECT_TITLE: Determining the mechanisms linking cell growth to the cell cycle in the liver

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-C(02)M]


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

ORG_CITY: NOTRE DAME

ORG_NAME: UNIVERSITY OF NOTRE DAME

ORG_STATE: IN

PHR: PROJECT NARRATIVE Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is characterized predominantly by alterations to the VHL gene which often results in the activation of a cellular protein called HIF (hypoxia inducible factor). The altered VHL protein exists in one of three different forms, and it was recently discovered that one of these forms is a potent inducer of ccRCC metastases. Following up on exciting preliminary observations, we will investigate how this tumor-promoting VHL isoform communicates with other cells in the tumor microenvironment, enabling the onset and spread of ccRCC.

PI_NAMEs: D'SOUZA-SCHOREY, CRISLYN  (contact)

PROGRAM_OFFICER_NAME: GEORGE, CHRISTINA DAWN

PROJECT_TERMS: Accounting;Affect;autosome;Behavior;Binding;Biochemical;Biological;Body System;cancer cell;cancer subtypes;cancer type;Cell Line;Cell model;Cell Proliferation;Cell surface;Cell Surface Proteins;cell type;Cells;Chromosomal Instability;Classification;Clear cell renal cell carcinoma;Communication;Complex;Conventional (Clear Cell) Renal Cell Carcinoma;Data;Development;Diagnosis;Disease;Endothelial Cells;Exhibits;Exons;extracellular vesicles;gain of function;Genes;Germ-Line Mutation;Human;Hypoxia Inducible Factor;Incidence;Individual;innovation;insight;intercellular communication;Investigation;Knowledge;Ligase;Lipids;Malignant Neoplasms;Mediating;Membrane;Molecular;Molecular Abnormality;mouse model;Mutation;Neoplasm Metastasis;Neoplasms;Neoplasms in Vascular Tissue;neoplastic cell;novel therapeutics;Nucleic Acids;Paracrine Communication;Pathologic;Pathology;Patients;Phenotype;Physiological;Pilot Projects;Play;Population;Pre-Clinical Model;Protein Isoforms;protein protein interaction;Proteins;Renal Carcinoma;Renal Cell Carcinoma;Research;response;RNA Splicing;Role;standard care;Surface;targeted treatment;Testing;Therapeutic;Tissues;translational potential;Treatment Protocols;tumor;Tumor Cell Line;tumor microenvironment;tumor progression;Tumor Promotion;Tumor Suppressor Proteins;tumorigenesis;tumorigenic;United States;Variant;variant detection;Vesicle;VHL gene;VHL protein;Von Hippel-Lindau Syndrome;Work;Xenograft procedure;young adult

PROJECT_TITLE: Pro-tumorigenic roles of a VHL isoform in Clear Cell Renal Cell Carcinoma


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Clinical Research;Disability Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Physical Activity;Prevention;Social Determinants of Health

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Older adults need transportation options that maximize their physical activity and social participation, regardless of disability status. This research will inform future planning and policy by highlighting components of accessible public transit systems which are associated with physical activity and social participation among older adults with disabilities. The knowledge gained will inform whether accessible and inclusive public transit options are a potential avenue to maximize health equity among older adults with disabilities.

PI_NAMEs: TWARDZIK, ERICA  (contact)

PROGRAM_OFFICER_NAME: TORRES, DELANY

PROJECT_TERMS: Accelerometer;Adult;Affect;Age;Aging;aging in place;Area;Automobile Driving;Award;Behavior;beneficiary;career;career development;Cognition;Communication;Communities;Complex;Data;data integration;Data Sources;density;Development;disability;Disability status;Disabled Persons;Disparity population;Elderly;end of life;Environment;Equity;Facility Designs;Family;Fellowship;Foundations;Friends;Future;Goals;Health;Health behavior;health determinants;health disparity;health equity;Health Status;healthy aging;Hearing;Home;human old age (65+);improved;Intervention;Investigation;Knowledge;lens;Link;longitudinal analysis;Measures;Mediating;Mediation;Medicare;Mentorship;mortality;Neighborhoods;older adult;Pathway interactions;Patient Self-Report;Persons;Phase;Physical activity;Physical shape;Policies;Population;Population Group;Population Heterogeneity;Positioning Attribute;Quality of life;Reduce health disparities;Religion;Reporting;Research;Research Personnel;Role;Sampling;Self Care;Services;social;social engagement;social epidemiology;social health determinants;Societal Factors;structural determinants;Surveys;System;Testing;Training;Transportation;transportation access;Travel;trend;Universities;Urban Developments;urban planning;Visit;Walking;Work

PROJECT_TITLE: Investigating the role of public transit on health behaviors among older adults with disabilities

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development Facilitating The Transition to Independence Study Section[AGCD-1]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Congenital Structural Anomalies;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences;Pediatric

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: Narrative This proposal is focused on understanding the structural link between genetic deficiencies and inherited diseases of the eyes and other tissues. Doing so will help us understand the mechanisms of retinal neurodegeneration and other cilium-associated pathologies and could lead to new therapeutic approaches.

PI_NAMEs: WENSEL, THEODORE G (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: Animal Model;appendage;Bardet-Biedl Syndrome;Carrier Proteins;Cell Death;Cellular Structures;Cilia;ciliopathy;Color;Computer software;Cryo-electron tomography;Deficiency Diseases;Development;Disease;Electron Microscopy;Electrons;Environment;Event;Exclusion;experimental study;Eye diseases;Fiber;Fluorescence;Fluorescence Microscopy;Functional disorder;Genes;Genetic;Genetic Techniques;Goals;Hereditary Disease;imaging approach;Imaging technology;improved;innovation;kinetosome;Lead;Light;Link;Membrane;Membrane Proteins;Microtubules;Molecular;molecular scale;mouse model;Mus;nanometer resolution;Nerve Degeneration;Noise;novel;novel therapeutic intervention;particle;Pathology;Pharmaceutical Preparations;Play;protein complex;protein function;Proteins;Resolution;restoration;Retina;Retinal Degeneration;Retinal Photoreceptors;retinal rods;Rod;Role;Route;Secondary to;Sensory;Shapes;Signal Transduction;Structure;Testing;three dimensional structure;Tissues;trafficking;Triplet Multiple Birth;ultra high resolution;Vertebrate Photoreceptors

PROJECT_TITLE: Cilium-associated structures in rod cells

STUDY_SECTION: BVS

STUDY_SECTION_NAME: Biology of the Visual System Study Section[BVS]


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;Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Precision Medicine;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE The proposed Leadership Award will synergize Dr. Rabinovici’s programmatic contributions in ADRD biomarkers with Dr. Possin’s contributions to clinical diagnosis and care models. The research program will validate cutting- edge tablet-based cognitive assessments and biomarkers to reimagine Alzheimer’s diagnosis that is precise, inclusive, and scalable, and that will identify appropriate candidates for disease modifying therapies. Supported by a multi-disciplinary team of co-investigators and consultants, and by leveraging the resources of the UCSF Alzheimer’s Disease Research Center and New IDEAS, the PIs will foster significant growth and depth of their mentoring program of diverse mentees to tackle the major challenges in the ADRD field.

PI_NAMEs: POSSIN, KATHERINE LAUREL;RABINOVICI, GIL DAN (contact)

PROGRAM_OFFICER_NAME: ELLIOTT, CERISE

PROJECT_TERMS: Address;African American;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease related dementia;Amyloid;Award;Behavioral;beneficiary;Biological Markers;Black race;blood-based biomarker;Brain imaging;Caregivers;Caring;Clinical;clinical care;clinical diagnosis;clinical phenotype;clinical practice;Cognition;Cognitive;cognitive testing;cohort;Dementia;dementia care;Diagnosis;Diagnostic;diagnostic accuracy;Differential Diagnosis;Disease;Enrollment;ethnic diversity;Fostering;Future;Goals;Growth;Health;health disparity populations;Hispanic;Impaired cognition;improved;Incentives;innovation;Latino;Leadership;Magnetic Resonance Imaging;Measures;Medicare;Mentors;Modeling;molecular pathology;multidisciplinary;Nerve Degeneration;Neurologist;novel;Outcome;Participant;Patients;Plasma;Population Heterogeneity;Positron-Emission Tomography;precision medicine;programs;Provider;Race;recruit;Research;Research Personnel;Resources;social health determinants;Surveys;Symptoms;synergism;Tablets;tau Proteins;tool;Work

PROJECT_TITLE: Reimagining Precision Medicine Approaches to AD Diagnosis


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Brain Disorders;Cancer;Clinical Research;Neurosciences;Rare Diseases

ORG_CITY: EVANSTON

ORG_NAME: ENDEAVOR HEALTH CLINICAL OPERATIONS

ORG_STATE: IL

PHR: A method that could improve the accuracy of MRI for brain tumors would be of great clinical benefit. Towards this end, we have developed a new class of pulse sequences, called T1 Relaxation-Enhanced Steady-State (T1RESS), that greatly improves the visibility of tumors in contrast-enhanced MRI by differentially suppressing the signal intensity of non-enhancing background tissues while maintaining the signal intensity of contrast- enhancing lesions. The primary hypothesis of this five-year grant proposal is that T1RESS will significantly improve the sensitivity for small brain metastases compared with existing MRI pulse sequences, while a secondary hypothesis is that the twofold improvement in tumor-to-brain contrast obtained with uT1RESS can be used to enable a substantial reduction in gadolinium-based contrast agent dosage.

PI_NAMEs: EDELMAN, ROBERT R. (contact)

PROGRAM_OFFICER_NAME: GRODZINSKI, PIOTR

PROJECT_TERMS: Adult;Anatomy;Appearance;Applications Grants;Biological Products;Blood;Blood Vessels;blood-brain barrier crossing;Brain;Brain Neoplasms;brain tumor imaging;cancer imaging;Cerebrum;Clinical;contrast enhanced;Contrast Media;cost;Darkness;Deposition;Detection;diagnostic accuracy;Disease;dosage;Dose;Enhancing Lesion;Equation;Fatty acid glycerol esters;Frequencies;Gadolinium;Goals;healthy volunteer;Image;image registration;Imaging Techniques;improved;Institution;Leptomeninges;Lesion;Magnetic Resonance Imaging;Metastatic malignant neoplasm to brain;Methods;Modeling;Morphologic artifacts;Neck;Neoplasm Metastasis;Nephrogenic Systemic Fibrosis;neuroimaging;Noise;novel;Ocular orbit;Patients;PET/CT scan;Phase;Physiologic pulse;Pilot Projects;Prognosis;Publishing;Radiosurgery;Relaxation;Research;Resolution;risk minimization;Scanning;Science;Sensitivity and Specificity;Signal Transduction;Site;skull base;Specificity;standard of care;Techniques;Time;Tissues;treatment planning;tumor;tumor diagnosis;Variant;Water

PROJECT_TITLE: Improved Detection of Cerebral Metastases using a using a Novel T1 Relaxation-Enhanced Steady-State (T1RESS) MRI Technique

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BOSTON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

ORG_STATE: MA

PHR: Narrative APOE4 is the major genetic risk factor for Alzheimer’s disease (AD), however we do not fully understand how APOE4-driven endolysosomal trafficking defects influence disease risk in human AD brain cells. The goal of this project is to understand the molecular mechanisms of APOE4 lipid-endolysosomal trafficking defect in human astrocytes and identify targets that can reverse the phenotype. Human iPSC-based model application and the knowledge gained from this proposal will be essential to the development of novel AD therapeutic modalities.

PI_NAMEs: TCW, JULIA  (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Acute;Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease patient;Alzheimer's disease risk;Alzheimer's disease therapeutic;Apolipoprotein E;apolipoprotein E-4;astrocyte progenitor;Astrocytes;Autophagocytosis;Autopsy;autosome;base editing;Biological Models;BODIPY;Brain;brain cell;brain endothelial cell;causal variant;cell type;Cholesterol;cholesterol biosynthesis;chronic demyelination;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR interference;CRISPR/Cas technology;Cuprizone;Data;Defect;Dementia;Demyelinations;Development;Disease;disorder risk;droplet sequencing;Drug Targeting;effective therapy;endophenotype;Endosomes;Excision;Exhibits;Functional disorder;Future;Genes;genetic risk factor;Genetic Screening;Genetic Transcription;genetic variant;genome wide association study;Genotype;Goals;Guide RNA;Human;human induced pluripotent stem cells;Immunodeficient Mouse;Impairment;In Vitro;in vivo;Intracellular Accumulation of Lipids;knock-down;Knock-out;Knowledge;Label;Late Onset Alzheimer Disease;lipid transport;Lipids;Longitudinal Studies;loss of function;Lysosomes;Measures;Mediating;Metabolic;Microglia;Modality;Modeling;Molecular;Molecular Chaperones;Myelin;Nerve Degeneration;Neuroglia;neuropathology;NFIA gene;novel;Organelles;Pathogenesis;Pathology;Pathway interactions;Phagocytes;Phagocytosis;Phagosomes;Phenotype;Phosphoric Monoester Hydrolases;Phosphotransferases;Process;progenitor;Regulator Genes;remyelination;Reporter;Research Project Grants;Risk;risk variant;RNA library;screening;Series;single-cell RNA sequencing;stem cell model;Symptoms;System;targeted treatment;Testing;Therapeutic;trafficking;transcription activator-like effector nucleases;transcription factor;Transcriptional Regulation;transcriptome;transcriptome sequencing;Transfection;Treatment Efficacy;uptake;Variant;Western Blotting;Xenograft procedure

PROJECT_TITLE: Elucidating endolysosomal trafficking dysregulation induced by APOE4 in human astrocytes

STUDY_SECTION: CMBG

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


ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative Dysregulation of proteostasis is implicated in a wide range of diseases including cancer, cardiovascular disease, and neurodegenerative diseases. Therefore, development of therapies that target proteostatic pathways would likely be beneficial to treat human disease. The studies proposed here will lead to the identification of novel properties of Dictyostelium discoideum that prevent protein aggregation, and this new insight may lead to the development of novel therapeutics.

PI_NAMEs: SCAGLIONE, KENNETH MATTHEW (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: Amoeba genus;Area;Biological;Biology;Biomedical Research;Cardiovascular Diseases;Cells;Development;Developmental Process;Dictyostelium;Dictyostelium discoideum;Disease;Factor Analysis;Fruit;Gene Family;Genes;Genetic Transcription;Goals;human disease;insight;interest;Investigation;Laboratories;Malignant Neoplasms;misfolded protein;model organism;Nature;Neurodegenerative Disorders;novel;novel therapeutics;Organism;Pathway interactions;Play;prevent;Property;protein aggregation;Protein Family;Proteins;proteostasis;proteostasis loss;Quality Control;Resistance;Role;targeted treatment;Testing;Therapeutic;therapy development;Time;Work

PROJECT_TITLE: Investigation into protein quality control pathways in Dictyostelium discoideum

STUDY_SECTION: MRAC

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Attention Deficit Hyperactivity Disorder (ADHD);Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Frontotemporal Dementia (FTD);Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurodegenerative;Neurosciences;Pediatric;Rare Diseases

PHR: PROJECT NARRATIVE Studies in animal models and humans support the notion that disease-causing mutations for frontotemporal dementia (FTD) and Alzheimer's disease (AD) may play critical roles in neurodevelopment. By studying children carrying mutations causing FTD or AD, this proposal will characterize and identify how early disease- specific neural circuit differences arise. These findings will reveal important insights into the underlying biology of these diseases and will determine how early biomarker trajectories in genetic FTD and AD diverge from trajectories in noncarriers.

PI_NAMEs: LEE, SUZEE EURIE (contact)

PROGRAM_OFFICER_NAME: ROVESCALLI, ALESSANDRA C

PROJECT_TERMS: Adult;Age;aged;Alzheimer's Disease;Amygdaloid structure;Animal Model;Attention;Attention deficit hyperactivity disorder;autism spectrum disorder;autistic children;autosome;behavior measurement;Behavioral Symptoms;behavioral variant frontotemporal dementia;Bilateral;Biological Markers;Biology;Brain;Child;Clinical;Cognitive;comparison control;Corpus striatum structure;Cross-Sectional Studies;Data;Differential Diagnosis;Disease;disease-causing mutation;DNA Sequence Alteration;Dominant Genes;Dyslexia;early detection biomarkers;Early identification;executive function;Family;Family member;frontal lobe;Frontotemporal Dementia;Functional Magnetic Resonance Imaging;Genetic;gray matter;Human;Inferior;insight;Insula of Reil;Language;Learning Disabilities;Left;Life;life span;Memory;Modeling;Mutation;mutation carrier;neural circuit;neural network;Neurobehavioral Manifestations;Neurodegenerative Disorders;neurodevelopment;Neurodevelopmental Disorder;neuroimaging;Pattern;Performance;Phase;Play;presenilin-1;Primary Progressive Aphasia;Resources;Role;Structure;Symptoms;Syndrome;white matter;Work;young adult

PROJECT_TITLE: Neurodevelopment in children from families with genetic frontotemporal dementia and Alzheimer’s disease

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Clinical Research;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: Project Narrative Fms-like tyrosine kinase 3 (FLT3) mutations are some of the most common mutations in acute myeloid leukemia. Phenylalanine 691 to leucine (F691L) mutations in AML occur following targeted FLT3 inhibitor therapy, making these types of AML especially difficult to treat. The proposed research will explore the mechanisms underlying this F691L mutation, aiming to target this exquisitely resistant form of cancer genetically and pharmacologically, with a goal of identifying novel targeted therapies against this high-risk group of leukemias.

PI_NAMEs: JONES, LAQUITA M (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Acute leukemia;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adaptor Signaling Protein;Affect;Affinity;Applications Grants;Binding;Binding Sites;Biological;Biology;cancer type;Cell Line;Cell Proliferation;Cell Survival;Chemicals;chemotherapy;Clustered Regularly Interspaced Short Palindromic Repeats;Codon Nucleotides;combinatorial;Combined Modality Therapy;CRISPR screen;Data;Dependence;Development;drug development;Engineering;Exhibits;experience;Exposure to;FLT3 gene;Gatekeeping;Gene Expression;Generations;Genes;Genetic;Goals;high risk population;Human;improved;In Vitro;in vivo;inhibitor;inhibitor therapy;knock-down;Leucine;leukemia;Leukemic Cell;Libraries;Malignant Childhood Neoplasm;Malignant Neoplasms;MAP Kinase Gene;Mediating;Modeling;Molecular Abnormality;Molecular Target;mutant;Mutate;Mutation;new therapeutic target;next generation;novel;novel therapeutics;Oncogenic;Outcome;Pathway interactions;Patients;Pediatrics;pharmacologic;Phenylalanine;Phosphotransferases;PI3K/AKT;Point Mutation;Prognosis;recruit;Recurrent disease;Refractory;Refractory Disease;Relapse;Reporting;Research;Resistance;resistance mechanism;Role;Sampling;Signal Pathway;Signal Transduction;Specificity;Stat5 protein;targeted treatment;Testing;Therapeutic;therapeutic candidate;therapeutic target;Time;tool;Toxic effect;whole genome

PROJECT_TITLE: Kinase-independent mechanism of resistance to FLT3 inhibitors in AML

STUDY_SECTION: NCI

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


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cerebral Palsy;Clinical Research;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rehabilitation

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: PROJECT NARRATIVE  Pediatric dysarthria is a disorder of speech movement that causes reduced speech intelligibility and negatively impacts quality of life for over half of children with cerebral palsy (CP), yet there is little evidence to guide its assessment and treatment. This research will compare the efficacy of a local, emphatic stress based speech modification strategy to two previously-studied global strategies (i.e., “loud” speech and slow rate) for 25 children with dysarthria secondary to cerebral palsy, and will identify mechanisms underlying intelligibility gains from these strategies. Results of this research will provide essential information about the “key ingredients” to successful use of speech modification strategies that can be leveraged to improve effectiveness of speech intervention for children with dysarthria.

PI_NAMEs: ALLISON, KRISTEN M. (contact)

PROGRAM_OFFICER_NAME: KOPF, LISA MARIE

PROJECT_TERMS: Acoustics;Address;Adolescent;Affect;Articulation;Cerebral Palsy;Child;Childhood;Clinical;Clinical Management;Communication;comparative efficacy;Cues;Data;Development;Dysarthria;Effectiveness;evidence base;Evidence based intervention;improved;individualized medicine;Intervention;Intervention Studies;kinematics;Knowledge;Lead;Loudness;Measures;Methods;Modeling;Modification;Motor;Movement;novel;Outcome;Population;Prevalence;Production;programs;Quality of life;Research;response;Secondary to;skills;social engagement;Spastic Cerebral Palsy;Speech;Speech Disorders;Speech Intelligibility;Speech Sound;Stress;successful intervention;Task Performances;Techniques;Treatment Effectiveness;Voice;Work

PROJECT_TITLE: Enhancing efficacy of speech modification strategies for pediatric dysarthria


NIH_SPENDING_CATS: Clinical Research;Genetics;Infectious Diseases;Malaria;Rare Diseases;Vector-Borne Diseases

ORG_CITY: LEGON

ORG_COUNTRY: GHANA

ORG_FIPS: GH

ORG_NAME: UNIVERSITY OF GHANA

PHR: Public Health Relevance: Malaria kills more than 400 million people in Africa each year, with the majority of fatalities occurring in children under the age of 5 in areas south of the Sahara. Control efforts have been scaled up in many parts of sub-Saharan Africa. However, these efforts are being hampered by resistance to commonly used insecticide for vector control. Results of these studies will help manage insecticide resistance and malaria control.

PI_NAMEs: AFRANE, YAW ASARE (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Africa;Africa South of the Sahara;African;Age;Area;Beds;Behavior;Biochemical;Bite;Child;Complex;Country;County;Culicidae;Cytochrome P450;Data;density;Development;Dose;Drosophila genus;Drug Metabolic Detoxication;Ecology;Effectiveness;Enzyme Inhibition;Enzymes;Evolution;Exposure to;Feeding behaviors;Frequencies;Gene Family;Genetic;Genetic Transcription;genome-wide;Genotype;Goals;Heterogeneity;Human;Insecticide Resistance;Insecticides;Kenya;Malaria;Measures;Mediating;Metabolic;Methods;Mutation;next generation;Outcome;Pattern;Persons;Phenotype;Population;Production;prospective;public health relevance;pyrethroid;Recording of previous events;Residual state;Resistance;resistant strain;response;Rest;Risk;Role;Sahara;scale up;Shapes;Site;synergism;transcriptome sequencing;transcriptomics;transmission process;Variant;vector;vector control;Vector Ecology;vector transmission

PROJECT_TITLE: Ecology and genetics of insecticide resistance in African malaria vectors

STUDY_SECTION: VB

STUDY_SECTION_NAME: Vector Biology Study Section[VB]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Genetics;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Project Narrative The abuse of opioids including heroin is at epidemic proportions in the USA. Our research is dedicated to expanding knowledge about molecular impairments directly in the brains of the human drug abusers to guide the development of new targeted medications.

PI_NAMEs: HURD, YASMIN L. (contact)

PROGRAM_OFFICER_NAME: TSAI, SHANG-YI ANNE

PROJECT_TERMS: abuse liability;addiction;Address;Anatomy;Animal Model;Animals;Area;Autopsy;Behavior;Biochemical;Biological;Biological Assay;Brain;Brain region;Cell Culture Techniques;cell type;Cells;Characteristics;Chronic;Cognitive deficits;cognitive function;Communities;Corpus striatum structure;Cytoskeletal Modeling;Cytoskeleton;Data;Dedications;density;Development;Disease;Dorsal;drug abuser;Drug Prescriptions;Economic Burden;Epidemic;Epigenetic Process;Female;Fluorescence;Foundations;Functional disorder;Future;FYN gene;Gene Expression;glutamatergic signaling;Glutamates;Goals;grasp;Harm Reduction;Health;healthcare burden;Heavy Drinking;Helping to End Addiction Long-term;Heroin;Heroin Abuse;heroin abuser;Heroin Dependence;heroin use;Human;human subject;hyperphosphorylated tau;Impairment;In Situ Hybridization;In Vitro;inhibitor;insight;Intervention;Investigation;knock-down;Knowledge;Link;male;Mediating;Medical;Microtubules;Modeling;Molecular;Molecular Neurobiology;Molecular Profiling;Molecular Target;Motivation;multidisciplinary;N-Methylaspartate;Neurobiology;Neurons;non-opioid analgesic;novel;novel therapeutics;Nuclear;Opiate Addiction;Opioid;opioid abuse;opioid epidemic;opioid exposure;opioid overdose;opioid use;opioid use disorder;Overdose;overdose death;Pathology;Patients;Pharmaceutical Preparations;pharmacologic;Phosphorylation;Phosphorylation Site;postsynaptic;prescription opioid;promoter;Rattus;Recording of previous events;Regulation;Relapse;Research;Resources;Rewards;Rodent;Rodent Model;Role;Science;Self Administration;Services;Signal Pathway;Signal Transduction;Sorting;Specificity;src-Family Kinases;System;targeted treatment;tau Proteins;tau-1;therapeutic development;Time;tool;transcriptome;transcriptome sequencing;translational potential;Translational Research;transmission process;United States;United States National Institutes of Health;Up-Regulation;Viral;Withdrawal

PROJECT_TITLE: Molecular Neurobiology of Human Opioid Use Disorder

STUDY_SECTION: PMDA

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


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Eye Disease and Disorders of Vision;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_DEPT: OPHTHALMOLOGY

PHR: NARRATIVE Large-scale volumetric voltage imaging is a powerful method in understanding brain function, yet posts profound technical challenges. We propose a mesoscopic oblique plane microscopy (Meso-OPM) to address the challenges and achieve >1.8 mm2 field-of-view, >0.1 mm depth penetration, and 1 KHz volume rate in imaging Voltron voltage indicators. We will test our technique in Zebra fish larvae, for the first time, offering recording across the whole nervous system to dissecting neural circuitry responsible for motor behaviors.

PI_NAMEs: YI, JI  (contact)

PROGRAM_OFFICER_NAME: ANDERSON, AFROUZ AZARI

PROJECT_TERMS: 3-Dimensional;Action Potentials;Address;Adopted;Algorithms;Animals;Area;Behavior;Biological;Bite;body position;Brain;Brain imaging;brain volume;Budgets;Central Nervous System;Code;Collection;Communication;Compensation;computerized data processing;Data;data analysis pipeline;Data Set;deep learning;deep learning algorithm;deep learning model;denoising;design;Detection;detector;Development;Dyes;Electronics;Eye;Fishes;flexibility;Fluorescence;Generations;Goals;Image;imaging system;improved;instrumentation;Kinetics;Label;Larva;Lasers;lens;Light;Maps;Mechanics;Membrane;Membrane Potentials;Methods;Microscopy;millimeter;Modeling;Motion;Motor;motor behavior;Mus;Nervous System;nervous system imaging;network architecture;neural;neural circuit;neuroimaging;Neurons;Neurosciences;Noise;optic flow;Optics;Pattern;Penetration;Performance;Photobleaching;Photons;Photoreceptors;Posture;processing speed;prototype;Resolution;response;Retina;Sampling;Scanning;self supervised learning;Signal Transduction;spatiotemporal;Speed;Spinal Cord;Stimulus;Structure;System;Techniques;Tectum Mesencephali;Testing;Three-Dimensional Imaging;three-dimensional modeling;Time;Tissues;Training;transmission process;Variant;visual stimulus;voltage;Work;Zebrafish

PROJECT_TITLE: Mesoscopic microscopy for ultra-high speed and large-scale volumetric brain imaging


NIH_SPENDING_CATS: Genetics;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: This proposal focuses on underlying mechanisms of mammalian embryonic development, the results of which will benefit the understanding of embryogenesis and human diseases caused by faulty development.

PI_NAMEs: XIAO, ZHUO ANDREW (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Adult;Biology;Brain;chromatin remodeling;Chromatin Structure;Development;DNA;DNA Methylation;DNA Transposable Elements;Embryonic Development;Epigenetic Process;Evolution;Human;human disease;Mammals;Mouse Embryonic Stem Cells;neoplastic cell;novel;Outcome;Placenta;Play;pluripotency;Regulation;Research;Role;Series;Specific qualifier value;stem cell fate;stem cells;Stress;Structure;Tissues;trophoblast;trophoblast stem cell;tumorigenesis

PROJECT_TITLE: A novel epigenetic mechanism in early embryogenesis

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Climate-Related Exposures and Conditions;Clinical Research;Genetics;Neurofibromatosis;Neurosciences;Orphan Drug;Rare Diseases;Skin Cancer

ORG_DEPT: DERMATOLOGY

PHR: Project Narrative Affecting up to 10% of the population, melanoma continues to be a deadly form of cancer for many patients despite recent advances in immunotherapies. A group of melanomas that harbor NF1 or SPRED1 mutations have particularly poor outcomes and developing new therapies will require a more thorough understanding of the affected signaling pathways. At the end of this research we expect to better understand the range of additional oncogenic mutations that cooperate with NF1 or SPRED1 loss and how these melanomas will respond to drugs that act on the RTK–RAS-MAPK pathway.

PI_NAMEs: YEH, IWEI  (contact)

PROGRAM_OFFICER_NAME: GHOSH-JANJIGIAN, SHARMISTHA

PROJECT_TERMS: Acral Lentiginous Malignant Melanoma;Address;Adjuvant;Affect;Binding;BRAF gene;Catalogs;Cell Line;Cell membrane;Cells;Clinical;Combined Modality Therapy;Complex;Data;Development;Disease;driver mutation;drug action;Environment;Epidemiology;ERBB2 gene;Ethnic Origin;Extinction;Feedback;foot;gain of function;Genetic;Genetic Engineering;genetic makeup;Genetically Engineered Mouse;Genome;Guanosine Triphosphate;Hand;Human Engineering;immune checkpoint blockade;Immunotherapy;improved;improved outcome;In Vitro;in vivo;Individual;inhibitor;innovation;insight;Invaded;Lead;Light;loss of function mutation;Malignant - descriptor;Malignant Neoplasms;MAP Kinase Gene;MEKs;Melanoma;Melanoma Cell;Melanoma patient;member;Membrane;Metastatic Melanoma;Mitogen-Activated Protein Kinases;mortality;mouse model;mucosal melanoma;Mucous Membrane;mutant;Mutation;Nail plate;NF1 gene;NF1 mutation;novel;novel therapeutics;Oncogenes;Oncogenic;Outcome;Pathway interactions;patient population;patient response;Patient-Focused Outcomes;Patients;Pattern;Population;Proliferating;ras GTPase-Activating Proteins;Receptor Protein-Tyrosine Kinases;Recurrence;Regimen;Research;Research Personnel;response;Role;Signal Pathway;Signal Transduction;Site;Skin;Skin tanning;Sun Exposure;Surface;targeted treatment;Testing;the sun;Therapeutic;therapeutic target;Treatment Efficacy;treatment strategy;Tumor Suppressor Proteins;Tumorigenicity;Ultraviolet Rays;Work;Xenograft procedure

PROJECT_TITLE: Defining the role of NF1 and SPRED1 loss in melanoma

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Neurosciences

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative We will investigate the planning-related mechanisms that enable human spoken interactions by measuring and manipulating cortical activity during vocal exchanges. The proposed research is relevant to the NIH's mission to contribute to the body of knowledge needed to help those who experience communication disorders.

PI_NAMEs: LONG, MICHAEL A (contact)

PROJECT_TITLE: Cortical Dynamics Underlying Interactive Language Use

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]