ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE This proposal will determine the various steric and electronic factors in designing stereoselective phosphorous catalysts for enantioselective acylations and tandem functionalizations. This proposal hypothesizes new, electron rich chiral P-catalysts which can function as a stereocontrolling element during several P-catalyzed steps. This proposal will use these catalysts for chemoselective P-catalysed dehydrative nitrile formation, an important transformation to the pharmaceutical community.

PI_NAMEs: ALI, SIRAJ ZAKI (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TITLE: Developing Selective P-catalysts for Dehydrative Transformations

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F04-S (20)]


ADMINISTERING_IC: HD

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Rehabilitation;Stroke

ORG_CITY: NEW YORK

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROLOGY

ORG_FIPS: US

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: This project is relevant to public health because it will generate fundamental knowledge about mechanisms of paired VNS in humans with chronic stroke. This knowledge will ultimately increase the efficacy of paired VNS by refining its delivery and identifying who is likely to benefit.

PI_NAMEs: HAYS, SETH ALANSON;SCHAMBRA, HEIDI  (contact);ZHONG, HUA JUDY

PROGRAM_OFFICER_NAME: BONNER, JOSEPH FRANCIS

PROJECT_TERMS: Address;Affective;Aftercare;Age;Area;Behavior;behavior test;Biometry;Blinded;Cervical;Chronic;chronic stroke;Clinical;clinical predictors;Clinical Trials Design;Cognition Disorders;Cognitive;cognitive system;Corticospinal Tracts;Crossover Design;demographics;Device or Instrument Development;Devices;Diffusion Magnetic Resonance Imaging;Disabling;effective therapy;Electric Stimulation;Forelimb;Functional Magnetic Resonance Imaging;functional plasticity;Human;Impairment;Implant;improved;Individual;Injury;insight;Intervention;Knowledge;Leadership;Long term disability;Magnetic Resonance Imaging;Measures;Mediating;Mediation;Mood Disorders;Motor;motor impairment;Motor Pathways;motor recovery;Movement;neural;neural network;neuroimaging;neurological rehabilitation;neuronal excitability;Neuronal Plasticity;neuroregulation;neurotransmitter release;Neurotransmitters;next generation;Pathway interactions;Patients;personalized medicine;Phase III Clinical Trials;post stroke;pre-clinical;predictive marker;Public Health;Randomized;Rehabilitation therapy;Research;Resources;response;Rodent;sex;Solid;Stroke;stroke model;stroke patient;Structure;successful intervention;Synapses;System;Task Performances;Testing;Therapeutic;therapeutic candidate;Time;Training;Transcranial magnetic stimulation;Treatment Efficacy;Treatment Protocols;treatment response;United States;Upper Extremity;vagus nerve stimulation;Vagus nerve structure;Work

PROJECT_TITLE: Mechanisms of paired vagus nerve stimulation in human chronic stroke

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Neurodegenerative;Neurosciences;Parkinson's Disease;Physical Activity

ORG_DEPT: NEUROSURGERY

PHR: Narrative Our preliminary and previous data show that exercise can increases striatal dopamine (DA) release in striatal slices from 12-month-old male and female mice, and that this is associated with an improvement in motor speed and coordination in mice of both sexes. This project will address several open questions in wild type and Parkinson's disease (PD) model mice, including the role of a growth factor, BDNF, in these benefits of exercise. Answering these questions could point to new cellular pathways that could be harnessed for PD therapeutics, and more generally, provide new mechanistic insight into the beneficial effects of exercise for brain health.

PI_NAMEs: RICE, MARGARET E (contact)

PROGRAM_OFFICER_NAME: KOEMETER-COX, ANDREW IAN

PROJECT_TERMS: Aerobic Exercise;Affect;Age;age effect;aged;Axon;Basic Science;Behavior;brain health;brain-derived growth factor;Brain-Derived Neurotrophic Factor;Clinical Sciences;Closure by clamp;cohort;Collaborations;comparison control;Corpus striatum structure;CRISPR/Cas technology;Data;Dependence;Development;diagnostic tool;Disease;Disease Progression;Dopamine;Dopamine D2 Receptor;dopamine replacement therapy;dopamine transporter;dopaminergic neuron;Dorsal;Dyskinetic syndrome;early onset;Exercise;experimental study;extracellular;Female;Fiber;Genetic;Glutamates;Goals;Image;improved;in vivo;insight;Left;Link;Long-Term Effects;male;Mediating;Midbrain structure;Monitor;Motor;motor behavior;motor deficit;motor impairment;mouse model;Mus;Mutation;Nerve Degeneration;neuron loss;Neuronal Plasticity;Neurons;new therapeutic target;nigrostriatal degeneration;nigrostriatal pathway;Nonpharmacologic Therapy;novel;novel strategies;novel therapeutic intervention;Nucleus Accumbens;old mice;Output;PARK2 gene;Parkin;Parkinson Disease;pars compacta;Pathologic;Pathway interactions;Patients;Performance;Periodicity;pharmacologic;Pharmacological Treatment;Photometry;Physiology;Process;Research;Research Personnel;Role;Rotation;Running;Scanning;sensor;sex;side effect;Slice;Speed;Substantia nigra structure;symptom treatment;Symptoms;Testing;Therapeutic;treatment strategy;uptake;Ventral Tegmental Area;voltage clamp;Wild Type Mouse

PROJECT_TITLE: Benefits of Exercise on Nigrostriatal Dopamine and Motor Behavior

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer

ORG_CITY: BOSTON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

ORG_STATE: MA

PHR: Project Narrative The mammalian target of rapamycin (mTOR) and Hippo pathways are key regulators of cell proliferation and tissue homeostasis that are frequently dysregulated in human cancers. This proposal aims to mechanistically define how STK25, a serine/threonine kinase, coordinates mTOR and Hippo signaling activities to maintain tissue homeostasis and limit tumorigenesis.

PI_NAMEs: HO, RACHEL XI-YEEN  (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Address;Adenocarcinoma;Affect;Area;Attenuated;Automobile Driving;Biochemical;Bioinformatics;Biological;Biological Assay;Cancer Biology;cancer cell;Cancer cell line;cancer subtypes;Cell Cycle Arrest;cell growth;cell growth regulation;Cell Proliferation;Cells;Cellular biology;chemical genetics;clinically relevant;Complex;Data;Development;Diffuse Lymphoma;Family;FRAP1 gene;Gene Expression;Gene Expression Profile;Gene set enrichment analysis;Genetic;Growth;Homeostasis;Human;Imaging Techniques;Impairment;In Vitro;in vivo;inhibitor;insight;Knock-out;Knockout Mice;LATS1 gene;LATS2 gene;liquid chromatography mass spectrometry;Maintenance;Malignant Neoplasms;Microscopy;Molecular;mouse model;Mus;Oncogenic;Output;overexpression;Pathway interactions;Penetrance;phosphoproteomics;Phosphorylation;Phosphotransferases;Play;programs;Protein-Serine-Threonine Kinases;Regulation;restoration;Role;Scientist;Serine;Signal Pathway;Signal Transduction;Sirolimus;skills;Soft tissue sarcoma;Sterility;success;Testing;Tissues;Training;Transcription Coactivator;transcriptomics;Transgenic Mice;tumor;Tumor Suppression;Tumor Suppressor Genes;Tumor Suppressor Proteins;tumorigenesis

PROJECT_TITLE: Defining the tumor suppressive mechanism of the kinase STK25

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09A-R (20)]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: GALVESTON

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE  In Alzheimer’s disease (AD), predictable spreading of tau pathology between functionally connected brain regions correlates well with progressive cognitive impairment, thus constituting a likely effective treatment target. The proposed study will evaluate the molecular mechanisms of pathological tau spreading within the framework of trans-synaptic tau spreading. Specifically, the results of this investigation will contribute to the fundamental knowledge about the molecular mediators of tau oligomer binding in human synapses, thus providing novel and translationally relevant avenues for future AD research.

PI_NAMEs: KADAMANGUDI, SHRINATH  (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TITLE: Mechanisms of trans-synaptic pathological tau spreading in the human brain

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03C-N (20)]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

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

ORG_CITY: BALTIMORE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Retinopathy of prematurity is a major cause of blindness in the U.S. and globally. Current treatments have significant side-effects and do not address the important problem of retinal avascularity. This research will investigate a new mechanism for reparative angiogenesis that could lead to new therapeutic strategies for this condition.

PI_NAMEs: DUH, ELIA J (contact)

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: angiogenesis;Angiogenesis Inhibitors;Aorta;Binding;Blindness;Blood Vessels;Childhood;Cytoplasmic Tail;Data;Developed Countries;Development;Diabetic Retinopathy;Disease;Early treatment;Endothelial Cells;Endothelium;Enzymes;Exhibits;experimental study;Extracellular Domain;Glycolysis;Goals;Health;Human;Hypoxia;In Vitro;in vivo;insight;intravitreal injection;Ischemia;knock-down;Knockout Mice;Lead;Ligand Binding;Mediating;Membrane;migration;Modeling;Molecular;mutant;neuronal guidance;Neurons;novel;novel therapeutic intervention;Oxygen;Pathologic;Pathologic Neovascularization;Pathway interactions;Patients;Phenotype;Physiological;plexin;Population;Process;receptor;Receptor Signaling;Recombinants;Regulation;Reporting;Research;Resolution;Retina;retinal angiogenesis;Retinal Diseases;retinal ischemia;Retinal Neovascularization;Retinopathy of Prematurity;revascularization;Role;Semaphorins;side effect;Signal Transduction;Source;Testing;Therapeutic;therapy development;Tissues;treatment strategy;Vascularization;Vision;Wild Type Mouse;Work

PROJECT_TITLE: Reparative angiogenesis in ischemic retinopathy

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


NIH_SPENDING_CATS: Brain Disorders;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: MADISON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Amblyopia, the most common form of monocular vision loss, is increasingly resistant to reversal with age. We propose a series of experiments to test the hypothesis that dark exposure followed by light reintroduction induces asymmetric changes in synaptic structure and neuronal excitability in primary visual cortex that promote the rejuvenation of plasticity in the adult visual cortex.

PI_NAMEs: QUINLAN, ELIZABETH MARY (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Adhesions;Adult;Age;aged;Amblyopia;Animal Model;area striata;Biological Assay;Blindness;Cells;Compensation;Darkness;Data;density;Development;Electron Microscopy;experience;experimental study;extracellular;Family Felidae;Functional Imaging;functional plasticity;Image;improved;in vivo;insight;Light;Mediating;Methods;MMP9 gene;Modeling;Molecular;Monocular Vision;Mus;Nervous System;neuronal excitability;Neurons;patch clamp;Pathway interactions;Peptide Hydrolases;Physiological;presynaptic;Proteins;Proteolysis;Proteomics;Recovery;Regulation;Rejuvenation;Resistance;Resolution;response;Rodent;Series;Structure;Synapses;synaptic function;Synaptic plasticity;Testing;therapy development;Transmission Electron Microscopy;Vision;Visual;Visual Cortex;visual deprivation;Visual System;Work

PROJECT_TITLE: Synaptic Plasticity in Young versus Aged Visual Cortex

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICN-Y (02)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Nutrition;Obesity;Prevention;Women's Health Research

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Males and females exhibit sexually dimorphic vulnerability to obesity-induced pathology in multiple tissues, including the brain. Our recent findings suggest that subcutaneous adipose tissue, which is more abundant in females, protects against brain inflammation and synaptic dysfunction in mice with dietary obesity. The proposed experiments manipulate subcutaneous fat and anti-inflammatory signaling between cerebrospinal fluid immune cells and parenchymal glia to elucidate the underlying mechanisms for neuroprotection. In doing so, we hope to understand why the 'apple-shaped,' but not the 'pear-shaped' body fat distribution predicts dementia risk in humans, with the long-term goal of identifying novel risk factors for cognitive impairment.

PI_NAMEs: STRANAHAN, ALEXIS M. (contact)

PROGRAM_OFFICER_NAME: BASU, RAJATAVA

PROJECT_TERMS: 4-Hydroxy-Tamoxifen;Abbreviations;Ablation;Adipose tissue;Adult women;Age-associated memory impairment;aging population;Alzheimer's Disease;Anatomy;Anti-Inflammatory Agents;Apple;Area;autocrine;Autoimmune Diseases;Behavioral;biological sex;Body fat;Brain;Cardiovascular Pathology;CD4 Positive T Lymphocytes;Cell Separation;Cells;Central Nervous System;Central obesity;Cerebrospinal Fluid;Cervical lymph node group;Chronic;Clinical Research;Cognition;Cognitive;cognitive testing;comorbidity;Cre driver;cytokine;Cytokine Signaling;Data;Dementia;dementia risk;Detection;Diabetes Mellitus;diet-induced obesity;dietary;dimorphism;Dissection;Drug or chemical Tissue Distribution;Electrophysiology (science);Encephalitis;Epidemic;Exhibits;Experimental Models;experimental study;Fatty acid glycerol esters;Feedback;Female;Flow Cytometry;Functional disorder;glial activation;Goals;Health;Height;High Fat Diet;Hippocampus;Homing;Human;Hypertension;IL4 gene;Image;Immune;Immunity;Immunologics;Impaired cognition;inducible Cre;inducible gene expression;Inflammation;innovation;insight;Integral Membrane Protein;Interleukin 4 Receptor;Interleukin-13;Interleukin-4;Leukocytes;Light;Link;Lipectomy;Lymphocyte;lymphocyte trafficking;Machine Learning;male;Maps;Masculine;Measures;Meningeal;Meninges;Metabolic;metabolic phenotype;Microglia;Morphology;Mus;Myeloid Cells;Natural Immunity;Neuroglia;Neuroimmune;neuroinflammation;Neurons;neuroprotection;neutralizing antibody;novel;Obesity;obesity risk;Overnutrition;Pathogenesis;Pathology;Pattern;Pear;Peripheral;Physiological;Pilot Projects;Population;Predisposition;Prevalence;Publishing;reconstruction;recruit;Regulation;Reporter;Reporting;response;Risk;Risk Factors;Role;Route;Sex Differences;sexual dimorphism;sham surgery;Shapes;Signal Transduction;Structure;subcutaneous;Synapses;T-Lymphocyte;Tamoxifen;Testing;Therapeutic;Tissue Transplantation;Tissues;Toxin;trafficking;Transplantation Surgery;Visceral;Weight;Woman;Women's study

PROJECT_TITLE: Adipose tissue distribution determines microglial regulation of hippocampal plasticity

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 EMS-B (02)]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences;Regenerative Medicine

ORG_CITY: East Greenwich

ORG_NAME: GORDON RESEARCH CONFERENCES

ORG_STATE: RI

PHR: PROJECT NARRATIVE As of 2012, over 20.6 million adult Americans and 285 million people worldwide suffered from low or no vision, and it is expected to more than double by 2050, making it a significant public health problem. This conference seeks to bring basic ocular researchers from the widest possible range of disciplines together with clinicians to promote understanding of visual system development and disease, and to develop new approaches for treating vision disorders. This meeting also promotes the six major objectives of the NEI Framework for Vision Research, most notably to “gather knowledge of the molecular basis of ocular health and disease” and “strengthen the pool of vision researchers”.

PI_NAMEs: KAY, JEREMY N (contact)

PROJECT_TERMS: Adult;Aging;American;Area;Attention;Biological;Biology;Brain;career;Cell Fate Control;cell fate specification;cell type;Cells;Chick;Collaborations;Communication;Communities;design;Development;directed differentiation;Discipline;Disease;Drosophila genus;endogenous stem cells;Ensure;Environment;Ethnic Origin;Event;Evolution;Eye;Eye Development;Eye diseases;Faculty;Fees;Fertilization;Fostering;Functional disorder;Funding;Funding Agency;Gender;Genetic;Geography;Goals;Health;Human;human disease;Human Genetics;Impairment;Individual;innovation;insight;Italy;Knowledge;lecturer;Link;Mediating;meetings;Mentorship;model organism;Modeling;Molecular;Mus;Natural regeneration;Nerve Degeneration;nerve stem cell;neural;nonhuman primate;novel;novel strategies;Organism;Participant;Pattern Formation;peer;Perception;Persons;Postdoctoral Fellow;Primates;Process;Public Health;recruit;Recurrence;repaired;Request for Proposals;Research;research and development;Research Personnel;Retina;Retinal Diseases;retinal regeneration;Scientist;Sensory;sensory system;Societies;Specific qualifier value;stem cell biology;Structure;Students;symposium;System;systems research;Tissues;translational impact;Travel;Underrepresented Minority;Vision;vision development;Vision Disorders;Vision research;vision science;Visual;visual processing;Visual System;Woman;Zebrafish

PROJECT_TITLE: 2024 Visual System Development Gordon Research Conference and Gordon Research Seminar

STUDY_SECTION_NAME: Special Emphasis Panel[ZEY1 VSN (04)]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Breast Cancer;Cancer;Women's Health Research

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: Project Narrative During metastasis, evidence suggests that tumor derived extracellular vesicles facilitate metastasis by initiating changes in the cellular constituents and extracellular matrix of the future metastatic site, resulting in the development of the premetastatic niche. Our goal is to utilize our engineered model of the premetastatic niche to determine the role that matrix dynamics, cellular compositions, and cellular plasticity have on metastatic colonization and drug resistance. These data will be critical for the development of novel therapies designed to treat the most lethal aspect of breast cancer.

PI_NAMEs: SOLORIO, LUIS  (contact);WENDT, MICHAEL KEITH

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: 3-Dimensional;Address;Architecture;Biological Models;Biology;Biomedical Engineering;breast cancer metastasis;Breast Cancer Patient;cancer cell;Cancerous;Cells;Cessation of life;Clinical;Coculture Techniques;colonization resistance;Complex;Cues;Data;design;Development;Disease;Disseminated Malignant Neoplasm;Distant;Drops;Drug resistance;Drug resistance pathway;drug sensitivity;Engineering;Environment;Enzymes;Event;Extracellular Matrix;Extracellular Matrix Proteins;extracellular vesicles;Failure;Fibroblasts;Fibronectins;Future;Genetic;Goals;Growth;Heterogeneity;host neoplasm interaction;Human;Image;Image Analysis;Immune;immunogenicity;improved;In Vitro;in vivo Model;Integrins;Invaded;Lung;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Mediating;Mediator;metastatic process;Modeling;mortality;mouse model;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel;novel therapeutics;Organ;Outcome;Pathway interactions;patient response;Patients;permissiveness;pharmacologic;Phenotype;Play;Population;pre-clinical;prevent;Primary Neoplasm;Process;Proteomics;quantitative imaging;response;Role;scaffold;Series;single-cell RNA sequencing;Site;Soil;Survival Rate;targeted treatment;Testing;Therapeutic;Therapeutic Agents;therapy design;therapy resistant;three dimensional cell culture;Tissues;transglutaminase 2;Treatment Efficacy;treatment response;tumor;Tumor Cell Invasion;tumor microenvironment;tumor progression;Tumor Tissue;Tumor-Derived

PROJECT_TITLE: Engineering the Premetastatic Niche

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BTC-D (02)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Narrative Lp(a) levels are a risk factor for Atherosclerotic Cardiovascular Disease. The levels are mostly genetically determined. The current proposal aims to understand how the genetic determinants of Lp(a) levels affect Lp(a) composition and function.

PI_NAMEs: REYES-SOFFER, GISSETTE  (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: Academic Medical Centers;Address;Affect;Aging;apolipoprotein Lp(a+);Atherosclerosis;Biological Markers;Biology;Black Populations;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular risk factor;Cardiovascular system;Cause of Death;Characteristics;Clinical;cohort;Collaborations;Copy Number Polymorphism;Data;Death Rate;Development;disability;Disease;Disease Outcome;Disease Pathway;disorder risk;ethnic difference;ethnic diversity;Ethnic Origin;Ethnic Population;Etiology;Event;exome sequencing;Frequencies;Genes;Genetic;genetic analysis;Genetic Determinism;genetic variant;genome sequencing;Genomics;Goals;Heart Diseases;Height;Hispanic Populations;in silico;Individual;Inflammatory;interest;Knowledge;Kringles;Life;Link;lipidome;lipidomics;Lipids;Lipoprotein (a);Lipoproteins;Maps;Measures;Metabolic Clearance Rate;Metabolism;Mission;multi-ethnic;National Heart, Lung, and Blood Institute;novel;Outcome;Participant;particle;Patient Self-Report;Phenotype;Physiology;Plasma;Production;Proteins;Proteome;Proteomics;Publishing;Race;Regulation;Research;Residual state;Risk;Risk Factors;Role;Scientist;Single Nucleotide Polymorphism;Technology;tool;United States National Institutes of Health;Variant;Washington;whole genome

PROJECT_TITLE: Unraveling the Complexities of Lp(a): From Genes to Function

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IVBH-D (02)]


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

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative Cardiac arrhythmia can be an early indicator of disrupted heart cell-cell junctional integrity, which can progress to advanced stages of pathologic heart remodeling and sudden cardiac death, with early-stage disease diagnosis remaining a challenge, complicating the development of targeted therapies. It is essential to understand the regulatory mechanisms in place that control protein expression and turnover at the cardiac cell-cell junction in order to identify critical mediators of this process which could be targeted for therapeutic intervention. In the proposed research project, I will leverage molecular and computational techniques to characterize junctional protein expression regulation dynamics and assess the efficacy of a candidate gene therapy reintroduction approach in the rescue of arrhythmia and subsequent heart failure in physiologically relevant disease models with the goal of discovering generalizable regulatory pathways which could be exploited for patient care.

PI_NAMEs: ELLIS, MATTHEW W (contact)

PROGRAM_OFFICER_NAME: LIDMAN, KARIN FREDRIKSSON

PROJECT_TERMS: 3' Splice Site;Address;Adhesions;Affect;Alternative Splicing;Arrhythmia;arrhythmogenic cardiomyopathy;Biological Models;Bypass;Candidate Disease Gene;candidate identification;Cardiac;Cardiac Myocytes;cardiac tissue engineering;Cells;Cellular Structures;Cessation of life;Classification;Clinic;clinical diagnosis;Complex;Computational Technique;Connexin 43;Connexins;desmoplakin;Desmosomes;Development;Diagnosis;Disease;disease diagnosis;disease model;disease phenotype;Disease Progression;DNA Sequence Alteration;driving force;effective therapy;efficacy evaluation;Electric Conductivity;Electrophysiology (science);engineered stem cells;experimental study;Gap Junctions;Gene Components;gene therapy;Genes;Genetic;Genetic Diseases;Goals;Heart;heart cell;Heart Diseases;Heart failure;heart function;Homeostasis;Human;human disease;human induced pluripotent stem cells;human model;improved;In Vitro;in vivo;in vivo Model;Individual;induced pluripotent stem cell;insight;Intercalated disc;Intercellular Junctions;Intervention;Knock-in Mouse;Life;Mechanics;Mediator;Modeling;Molecular;Molecular Analysis;Molecular Computations;molecular modeling;mortality;mouse model;Mus;mutant;Mutant Strains Mice;Mutate;Mutation;Myocardial dysfunction;Myocardium;novel;Outcome;Pathogenesis;Pathologic;Patient Care;patient derived induced pluripotent stem cells;Patients;Penetrance;Persons;Physiological;plakophilin 2;posttranscriptional;Prevalence;prevent;Process;Prognostic Marker;protein complex;protein degradation;protein expression;Proteins;Proteomics;proteostasis;Regulation;Regulatory Pathway;Research Project Grants;restoration;RNA;RNA Binding;RNA Splicing;RNA-Binding Proteins;Role;scaffold;Signal Transduction;Site;Splice-Site Mutation;stem cell model;sudden cardiac death;System;targeted treatment;Techniques;Testing;Therapeutic;therapeutic development;Therapeutic Intervention;therapeutic target;Tissue constructs;Tissue Engineering;Tissues;Transcript;transcriptomics;Translating;translational impact;United States;Ventricular;Work

PROJECT_TITLE: Characterizing regulatory mechanisms of desmosomal protein expression in arrhythmogenic cardiomyopathy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-K (20)]


NIH_SPENDING_CATS: Hypertension

PHR: PROJECT NARRATIVE The 2024 GRC on Angiotensin will focus on the latest advances in the renin-angiotensin-aldosterone system (RAAS), from discovery science to clinical impact. The highlight will be the interplay between RAAS and other hormonal systems, how this influences interorgan communications from cell signaling to systems biology, technological innovation and drug discovery.

PI_NAMEs: PRIETO, MINOLFA C (contact)

PROGRAM_OFFICER_NAME: VARAGIC, JASMINA

PROJECT_TERMS: Adipose tissue;Angiotensins;Award;Basic Science;biological systems;Biomedical Engineering;Blood Pressure;Blood Vessels;Brain;Canada;Cardiovascular Diseases;Cardiovascular system;career;career development;Clinical;Clinical Sciences;Collaborations;Communication;Communities;Data;Data Scientist;Denmark;design;Development;Discipline;Disease;Distant;Doctor of Philosophy;drug discovery;Electrolytes;Endocrine system;Event;Fostering;Functional disorder;Funding;Future;Gender;Goals;graduate student;Grant;Health;Health Sciences;Heart;Homeostasis;Human Biology;human disease;Immune;Italy;Kidney;Kidney Diseases;Knowledge;Lead;Leadership;Liquid substance;Liver;Location;meetings;Mentors;Metabolic Diseases;Minority Groups;minority student;Mission;National Heart, Lung, and Blood Institute;novel therapeutics;Organ;Organelles;Pathologic Processes;Postdoctoral Fellow;Productivity;programs;Renaissance;Renin-Angiotensin-Aldosterone System;Research;Research Personnel;Resort;Role;Science;Scientist;Self Management;Signal Transduction;success;symposium;System;Systems Biology;systems research;technological innovation;tool;Translational Research;Travel;undergraduate student;Underrepresented Minority;Underrepresented Students;United States National Institutes of Health;Universities;Woman;Women Physicians;Writing

PROJECT_TITLE: 2024 Angiotensin Gordon Research Conference and Seminar

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-G (O3)]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Gene Therapy;Genetics;Hematology;Orphan Drug;Primary Immunodeficiencies;Rare Diseases;Regenerative Medicine;Sickle Cell Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE Gene therapies can definitively treat genetic blood diseases like Sickle Cell Disease, Severe Combined Immunodeficiency (“Bubble Boy Disease”), and Bone Marrow Failure disorders without requiring bone marrow transplant from another individual. However, current gene therapy treatment approaches rely on collection of blood stem cells by a medical procedure from the bone marrow or peripheral blood, then complex manufacture of gene modified blood stem cells outside of the body, and finally transplant of the gene modified blood stem cells back to the patient after first treating the patient with high-dose chemotherapy to allow for blood stem cell replacement. In this proposal, building from our expertise in virus engineering, gene editing, and disease biology, we aim to develop a novel gene therapy approach that could be administered directly to a patient’s blood stem cells by vein, thereby avoiding stem cell collection, complex cell manufacture, and toxic chemotherapy.

PI_NAMEs: BAUER, DANIEL EVAN (contact);BRENDEL, CHRISTIAN

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Address;Autologous;Back;base editor;Biodistribution;Biology;Bone Marrow;Bone marrow failure;Bone Marrow Transplantation;boys;Cell Compartmentation;Cell Surface Receptors;Cells;cellular transduction;chemotherapy;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Collection;Complex;Disease;DNA Integration;Dose;Endogenous Retroviruses;Engineering;Engraftment;Enhancers;first-in-human;flexibility;Frequencies;gene correction;Gene Delivery;Gene Modified;gene therapy;Gene Transfer;gene transplantation for gene therapy;Genes;Genetic;Genetic Engineering;genetic manipulation;genome editor;genotoxicity;Glycoproteins;Goals;Guide RNA;Hematological Disease;Hematopoietic Stem Cell Mobilization;Hematopoietic stem cells;Hemoglobin;High Dose Chemotherapy;Human;humanized mouse;IL2RG gene;improved;In Vitro;in vivo;Individual;innovation;Interleukin 2 Receptor Gamma;Interleukin-2;Lentivirus Vector;manufacture;Mediating;Medical;Mendelian disorder;Modality;Modification;Mus;Mutation;Myeloablative Chemotherapy;nanobodies;new technology;novel;novel therapeutic intervention;Papio;particle;patient population;Patients;peripheral blood;Phenotype;Point Mutation;Population;pre-clinical;Procedures;Production;receptor;Retroviral Vector;Ribonucleoproteins;Risk;Safety;screening;Severe Combined Immunodeficiency;Shwachman-Diamond syndrome;Sickle Cell Anemia;Specificity;stem cell gene therapy;stem cell replacement;stem cells;Stress;success;System;T-Lymphocyte;Technology;technology platform;Testing;Therapeutic;therapeutic genome editing;therapeutic target;tool;Toxic effect;Transgenes;Transplantation;Validation;vector;Veins;Viral;Virus;Virus-like particle;X-Linked Severe Combined Immunodeficiency

PROJECT_TITLE: In vivo hematopoietic stem cell genetic modification by viral particles

STUDY_SECTION: TAG

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


NIH_SPENDING_CATS: Diabetes;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

PHR: Diabetic retinopathy is a major cause of blindness worldwide, and there is a great need to identify new molecular targets. Current anti-VEGF drugs address only advanced stages of disease and are only partially effective. This research will investigate soluble guanylate cyclase as a novel regulator of DR and shed light into its various potential effects, providing a new molecular target for therapy.

PROGRAM_OFFICER_NAME: SHEN, GRACE L

PROJECT_TERMS: Address;bevacizumab;Binding;Blindness;Blood capillaries;Blood flow;Blood Vessels;Blood-Retinal Barrier;cell type;Cells;cGMP production;Clinical Trials;conditional knockout;Cyclic GMP;Cytoprotection;Data;Development;Diabetes Mellitus;diabetic;Diabetic Retinopathy;Disease;Disease Progression;Early treatment;Elements;Endothelial Cells;Enzymes;Functional disorder;Future;Glucose;Heme;heme a;In Vitro;in vivo;Inflammatory;insight;interest;Knockout Mice;Learning;Light;Modeling;Molecular Target;molecular targeted therapies;Nature;Nerve Degeneration;Neuronal Dysfunction;Neurons;neuroprotection;neurovascular unit;Nitric Oxide;novel;oxidation;Oxidative Stress;Pericytes;Pharmaceutical Preparations;pharmacologic;Predisposition;Prosthesis;protective factors;Publishing;Research;Retina;Rodent Model;Role;Signal Pathway;Signal Transduction;Smooth Muscle Myocytes;Soluble Guanylate Cyclase;Streptozocin;stressor;Systemic disease;Therapeutic;Therapeutic Effect;therapeutic target;Time;Tissues;translational potential;Vascular Diseases;Vascular Smooth Muscle;Work

PROJECT_TITLE: Soluble guanylate cyclase in diabetic retinopathy


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: PROJECT NARRATIVE High prevalence of severe cocaine use disorder among patients and the lack of FDA-approved treatment for cocaine use disorder demonstrates the critical need to identify new potential therapeutic targets for cocaine use disorder. The goal of the proposed research is to further our understanding of neural circuits that drive cocaine reinforcement. To this end, the proposed research will define how cocaine recruits an endogenous opioid peptide released from neurons in the striatum to alter striatal circuit functioning and drive cocaine taking and seeking.

PI_NAMEs: MATSUMURA, KANAKO  (contact)

PROGRAM_OFFICER_NAME: FALCON-MORALES, EDGARDO

PROJECT_TERMS: Abstinence;Acceleration;Address;Affect;antagonist;Attenuated;Automobile Driving;Behavior;Behavioral;behavioral study;Brain;career;Catheters;Cells;Closure by clamp;Cocaine;cocaine exposure;cocaine reward;cocaine seeking;cocaine self-administration;cocaine use;Cocaine use disorder;Cocaine withdrawal;Communication;conditioning;Corpus striatum structure;Cues;Data;Diagnosis;Disinhibition;Dopamine;Dopamine D2 Receptor;Dose;DSM-V;effective therapy;Electrophysiology (science);endogenous opioids;Enkephalin Receptors;Enkephalins;Exhibits;Extinction;FDA approved;Fellowship;gamma-Aminobutyric Acid;Globus Pallidus;Goals;High Prevalence;Immunohistochemistry;Implant;improved;Injections;insight;Intake;Knock-out;Knockout Mice;Laboratories;Learning;maladaptive behavior;Measures;Mediator;meetings;Mental Depression;Messenger RNA;Methods;motivated behavior;Motivation;Mus;neural circuit;neurobiological mechanism;Neurobiology;neuronal excitability;Neurons;Neurosciences;new therapeutic target;novel;Nucleus Accumbens;Opioid;Opioid Peptide;Opioid Receptor;optogenetics;Patients;Pharmaceutical Preparations;pharmacologic;Play;Positioning Attribute;Postdoctoral Fellow;postsynaptic;preference;presynaptic;prevent;Procedures;Psychological reinforcement;receptor;Recording of previous events;recruit;Research;Resources;response;Rewards;Role;Saline;Self Administration;skills;Slice;Stimulus;Substance Use Disorder;Synapses;System;Techniques;Testing;Texas;therapeutic target;Training;transmission process;Universities;voltage;Whole-Cell Recordings;Withdrawal

PROJECT_TITLE: Recruitment of striatal enkephalin by cocaine as a substrate for striatopallidal circuit adaptations and cocaine seeking

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02A-W (20)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Coronaviruses;Coronaviruses Diagnostics and Prognostics;Emerging Infectious Diseases;Infectious Diseases

ORG_DEPT: BIOCHEMISTRY

PHR: PROJECT NARRATIVE This proposal aims to develop a set of degradable bioplastic materials for point-of-care microfluidic diagnostic devices.

PI_NAMEs: SIA, SAMUEL K (contact)

PROGRAM_OFFICER_NAME: SASTALLA, INKA I

PROJECT_TERMS: 2019-nCoV;Acetates;Adoption;American;Architecture;Biological Assay;Cell Culture Techniques;Cellulose;Characteristics;Clinical;Complex;Compost;Consumption;COVID-19 detection;COVID-19 pandemic;Custom;cytotoxicity;detection method;detection test;Devices;Diagnostic;diagnostic assay;Diagnostic Equipment;diagnostic platform;Diagnostic Procedure;Ecosystem;Environmental Health;Environmental Impact;Equipment;Equity;fabrication;Fluorescence;Fossil Fuels;Future;gut inflammation;Health;Healthcare;Home;Human;Human body;Immune System Diseases;improved;innovation;interest;Laboratories;landfill;lateral flow assay;Life;Life Cycle Stages;Link;Mainstreaming;Malignant Neoplasms;manufacture;marine;Methods;Microfluidic Microchips;Microfluidics;molecular diagnostics;nasal swab;novel;nucleic acid detection;Nucleic Acids;Oceans;Oils;particle;Performance;Plants;Plastics;point of care;point-of-care diagnostics;Poison;poly(lactic acid);polycarbonate;Polymerase Chain Reaction;Polymethyl Methacrylate;Production;Property;respiratory;Risk;Sampling;Source;Specimen;System;Techniques;Testing;thermostability;Thinking;Tissues;uptake;usability;Viral Antigens;viral detection;Virus;wasting;Work

PROJECT_TITLE: Degradable bioplastics for microfluidic diagnostic assays towards improved environmental and human health

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-M (82)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Genetics;Infectious Diseases;Lung;Rare Diseases;Tuberculosis

ORG_CITY: SAN ANTONIO

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: PROJECT NARRATIVE Alveolar macrophages (AMs) are a critical cell population that have an important role in healthy lung function and lipid metabolism while also being the main cellular niche for Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), a global health problem. We will use a novel model for human AMs to investigate an understudied class of transcription factors linked to AM function and TB. We seek to determine the role of the NR4A family of nuclear receptors in macrophage function and host defense against Mycobacterium tuberculosis infection in order to deepen our understanding of AM biology and aid in identification of novel targets for host- directed therapies against TB.

PI_NAMEs: SIMPER, JAN  (contact)

PROGRAM_OFFICER_NAME: MENDEZ, SUSANA

PROJECT_TERMS: Address;Agonist;Alveolar;Alveolar Macrophages;Alveolus;Atherosclerosis;Biology;Biomedical Research;career;career development;Cause of Death;CD36 gene;Cell surface;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Communicable Diseases;Communication;Complement;Containment;Core Facility;Critical Thinking;Data;Data Analyses;design;Development;Disease;DNA Binding;Drug resistance;Energy-Generating Resources;Enzyme-Linked Immunosorbent Assay;ERG gene;experimental study;Family;Family member;Fellowship;Flow Cytometry;Future;Gases;Genetic Transcription;global health;Goals;Growth;Homeostasis;Host Defense;Human;human model;Imaging Techniques;Immune response;Immunologic Factors;improved;In Vitro;Individual;Infection;Infectious Agent;Inflammation;Inflammatory;Inflammatory Response;insight;Investigation;Journals;knock-down;Knock-out;Label;Laboratories;Learning;Ligand Binding Domain;Link;lipid metabolism;lipid transport;Lipids;Lipoproteins;Literature;Lung;lung health;Macrophage;Measures;Mediating;member;Mentorship;Metabolism;microbial;Modeling;monocyte;Mus;Mycobacterium tuberculosis;Myeloid Cells;N-terminal;novel;novel therapeutic intervention;NR4A1 gene;NR4A2 gene;Nuclear Family;Nuclear Receptors;Orphan;overexpression;pathogen;Pathogenesis;Pathology;Pathway interactions;peripheral blood;Phagocytes;Phagosomes;pharmacologic;Phase;Phenotype;Population;PPAR gamma;prevent;Proteins;Pulmonary Alveolar Proteinosis;pulmonary function;Pulmonary Surfactants;Quantitative Reverse Transcriptase PCR;receptor expression;Recycling;Reporting;Research;Research Institute;Resistance;Resources;Respiration;response;Role;scavenger receptor;Shapes;Signal Pathway;Signal Transduction;skills;Small Interfering RNA;Surface;surfactant;targeted treatment;Technical Expertise;Techniques;Texas;tissue culture;trafficking;Training;Transactivation;transcription factor;Tuberculosis;tuberculosis treatment;uptake;Western Blotting;Work

PROJECT_TITLE: Macrophage NR4A nuclear receptors in tuberculosis pathogenesis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07A-B (20)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Brain Disorders;Clinical Research;Machine Learning and Artificial Intelligence;Mental Health

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PROJECT NARRATIVE Delirium, or acute confusional state, affects up to 7 million hospitalized older adults annually and is associated with long-term declines in cognition and function. Medications are thought to be the cause of up to 36% of delir- ium and be contributory to an even higher percentage but are surprisingly understudied, with studies to date focusing on only a few medications and being only modest quality. In this secondary data analysis, we will apply machine learning data mining methods to a large electronic health record database with a decade of delirium as- sessments to comprehensively examine the risk of delirium due to medications, which in turn will lead to improved management for this serious but often overlooked disorder.

PI_NAMEs: KENNEDY, RICHARD E (contact);SKAINS, RACHEL MICHELLE

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Acute;acute care;Admission activity;Adult;Affect;Alabama;Algorithms;Anatomy;Benzodiazepines;Calcium Channel Blockers;care costs;Categories;Chemicals;Code;Cognition;Cognitive;Combination Medication;Confusion;Data;Data Analyses;data mining;Databases;Delirium;Development;Dihydropyridines;Discipline of Nursing;Disease;dosage;Dose;Drug Combinations;Drug Prescriptions;Elderly;Electronic Health Record;Functional impairment;Guidelines;Health system;Hospitalization;Hospitals;Hour;human old age (65+);Impaired cognition;improved;Individual;Inpatients;Institutionalization;Intervention;Knowledge;Long-Term Care for Elderly;Machine Learning;Maps;Methods;mortality risk;multidimensional data;Names;Nursing Staff;older adult;Opioid;Patients;Pattern;Perioperative;Pharmaceutical Preparations;Population;postoperative delirium;random forest;response;Risk;Risk Factors;Risk Management;risk prediction model;Role;Sample Size;screening;screening program;Source;Standardization;systematic review;Testing;Therapeutic;Universities;virtual;ward

PROJECT_TITLE: Comprehensive Assessment of Delirium Risk due to Medications

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Emerging Infectious Diseases;Hematology;Immunization;Infectious Diseases;Influenza;Lung;Pain Research;Pediatric;Pneumonia;Pneumonia and Influenza;Prevention;Rare Diseases;Sickle Cell Disease;Vaccine Related

ORG_CITY: NEW HAVEN

ORG_DEPT: PEDIATRICS

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE We propose a detailed interrogation and a systems approach to identify molecular signatures of disease outcomes and response to vaccination to support identifying relevant mechanisms for potential therapeutic and vaccination strategies in a dysregulated inflammatory milieu among children with sickle cell disease.

PI_NAMEs: SHAW, ALBERT C;YILDIRIM, INCI BURCIN (contact)

PROGRAM_OFFICER_NAME: PRABHUDAS, MERCY R

PROJECT_TERMS: Acute;acute chest syndrome;adaptive immunity;Adult;Affect;African American population;Age;age related;Amino Acid Substitution;Antibody Response;Antigens;B-Lymphocyte Subsets;B-Lymphocytes;beta Globin;Biological Assay;Birth;Boston;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Child;Childhood;Chronic;Clinical;clinical care;cohort;Collaborations;Color;Communicable Diseases;comparison control;Computational Biology;Disease;Disease Outcome;Enzyme-Linked Immunosorbent Assay;Erythrocyte Membrane;Flow Cytometry;Genetic;Genetic Transcription;Goals;Hemagglutination;Hematological Disease;Heme;hemoglobin polymer;Hemolysis;Human;Immune;Immunoglobulin A;Immunoglobulin G;Immunoglobulin M;immunological status;Immunologics;Immunology;Impairment;improved;In Vitro;Income;Individual;Infection;Inflammation;Inflammatory;inflammatory milieu;influenza pneumonia;Influenza vaccination;influenza virus vaccine;Infrastructure;Innate Immune Response;Innate Immune System;insight;Intervention;Life;Life Expectancy;Ligands;Link;metabolomics;Methods;Molecular;Molecular Profiling;Mononuclear;Morbidity - disease rate;mortality;Natural Immunity;novel;older adult;Outcome;Pain;Patients;Pattern;Pattern recognition receptor;Pediatric Hospitals;Peripheral;Plasma;Pneumococcal conjugate vaccine;Pneumococcal Infections;Pneumococcal vaccine;Population;programs;prospective;proteomic signature;Proteomics;Pulmonary Hypertension;receptor function;Resources;response;Risk;Sampling;seasonal influenza;Series;Serotyping;Shapes;Sickle Cell;Sickle Cell Anemia;single cell analysis;Streptococcus pneumoniae;Stroke;System;Systems Biology;T cell response;T-Lymphocyte;Therapeutic;Toll-like receptors;transcriptomics;United States;Vaccination;vaccination strategy;vaccine response;Vaccines;Vulnerable Populations;Whole Blood;whole genome;young adult

PROJECT_TITLE: Immune signatures of vaccine responses in children with sickle cell disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 DCAI-U (02)]


ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative The pathophysiology of pulmonary fibrosis relies on repeated local micro-injuries to the alveolar epithelium triggering DNA damage, cell death, and aberrant tissue remodeling. Elevated levels of cell-free DNA, derived from cell stress or cell death, activate the cGAS-STING pathway inducing interferon and pro-inflammatory cytokine expression. This proposal seeks to define a causal relationship between cGAS-STING, inflammation, and aberrant lung tissue remodeling.

PI_NAMEs: RIDGE, KAREN M (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: Ablation;Agonist;AGTR2 gene;alveolar epithelium;Alveolar Macrophages;Animal Model;Asbestos;autoinflammatory diseases;Binding;Bleomycin;Cell Death;cell free DNA;cell injury;Cell Nucleus;Cells;Cellular Stress;Cellular Structures;Cessation of life;Choristoma;Chronic;Code;Collagen;Connective Tissue Diseases;COVID-19;cytokine;Cytoplasm;Cytosol;Data;Diagnosis;DNA;DNA Binding;DNA Damage;ds-DNA;Endoplasmic Reticulum;endoplasmic reticulum stress;Environmental and Occupational Exposure;Epithelial Cells;Epithelium;exodeoxyribonuclease;Experimental Designs;Fatal Outcome;FDA approved;Fibrosis;fibrotic lung;fibrotic lung disease;Functional disorder;gain of function mutation;Gene Activation;gene interaction;Genes;Genetic;Golgi Apparatus;Histologic;idiopathic pulmonary fibrosis;immunopathology;improved;infancy;Inflammation;Inflammatory;injured;Injury;Interferons;Interstitial Lung Diseases;IRF3 gene;Ligands;loss of function;Lung;Lung Compliance;Lung Diseases;lung injury;lung repair;Malignant Neoplasms;Mediating;Molecular;monocyte;mortality;mouse model;Mus;mutant;NF-kappa B;Organelles;Pathway interactions;Patients;PERK kinase;Pharmaceutical Preparations;pharmacologic;Phase;Physiological;Population;Positioning Attribute;Predictive Factor;premature;Proteins;Pulmonary Fibrosis;Radiation;recruit;Recurrence;Reporting;Research;Respiratory Failure;Role;sensor;Signal Transduction;Stimulator of Interferon Genes;STING1 gene;Stress;Structure of parenchyma of lung;Systemic Scleroderma;Techniques;Testing;Time;tissue repair;Tissues;trafficking;transcriptomics;Transitional Cell;TREX1 gene;Vascular Diseases;Vimentin;Virus Diseases

PROJECT_TITLE: Elucidating the Role of cGAS-STING in Lung Tissue Repair and Remodeling

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

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

ORG_DEPT: GENETICS

PHR: Project Narrative Alcohol-associated liver disease (ALD) is one of the leading causes of morbidity and mortality worldwide among chronic liver diseases; unfortunately, no FDA-approved treatments are available, due to an incomplete understanding of its molecular mediators. The objectives of this project are to discover the new function of the serine-arginine protein kinase 2 (SRPK2) on alcohol-induced pre-mRNA splicing in hepatocytes, to elucidate how SRPK2-mediated regulation of pre-mRNA splicing modulates alcohol-induced abnormalities in lipid metabolism in ALD, and to investigate whether targeting SRPK2 by fibroblast growth factor 21 (FGF21), a hepatocyte-derived hormone, delays and reverses the progression of ALD. The proposed research is relevant to the mission of NIAAA and public health because the knowledge gained may provide a rationale for designing innovative therapeutic strategies, such as a long-acting form of FGF21, as pharmacological interventions for human ALD.

PI_NAMEs: ZANG, MENGWEI  (contact)

PROGRAM_OFFICER_NAME: LIN, LI

PROJECT_TERMS: Affect;alcohol response;Alcoholic Liver Diseases;Alcohols;Alternative Splicing;analog;Arginine;Attenuated;Biochemical;Cholesterol;Cholesterol Homeostasis;chronic liver disease;Clinical Trials;Coupled;Data;Dependovirus;design;Diabetes Mellitus;efficacy evaluation;Elements;Event;FDA approved;FGF2 gene;fibroblast growth factor 21;gain of function;Gene Delivery;Gene Expression;Genetic Transcription;Hepatic;Hepatocyte;Hormones;Human;In Vitro;in vivo;innovation;insight;Intervention;knock-down;Knockout Mice;Knowledge;Link;lipid biosynthesis;lipid metabolism;lipidomics;Lipids;lipine;Liver;Liver diseases;loss of function;Mediating;Mediator;Messenger RNA;Metabolic;Methods;Mission;Molecular;Morbidity - disease rate;mortality;mouse model;mRNA Precursor;Mus;National Institute on Alcohol Abuse and Alcoholism;new therapeutic target;novel;novel therapeutic intervention;overexpression;Pathogenesis;Pathology;Pathway interactions;pharmacologic;Pharmacology Study;Phosphorylation;Pilot Projects;pre-clinical;problem drinker;Process;Protein Kinase;Proteins;Proteome;Public Health;Regulation;Research;RNA Splicing;Rodent;Role;Serine;Signal Transduction;SRE-1 binding protein;Techniques;Testing;Therapeutic;therapeutic candidate;Therapeutic Intervention;therapeutic target;transcription factor;transcriptome;transcriptome sequencing;Transgenic Mice;Triglyceride Metabolism;Triglycerides

PROJECT_TITLE: Deciphering RNA Splicing Control of Lipid Metabolism and Alcoholic Liver Injury

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 KUDS-Y (04)]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Genetics;Immunization

ORG_CITY: BOZEMAN

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: MONTANA STATE UNIVERSITY - BOZEMAN

ORG_STATE: MT

PHR: PROJECT NARRATIVE CRISPR systems are diverse, RNA-guided, adaptive immune systems that provide sequence-specific defense against invading nucleic acids. In this fellowship application, I present specific experimental aims which are linked to training objectives that will provide critical mechanistic insight towards the biological function of a unique class of type III-B CRISPR systems physically linked to elements of toxin-antitoxin systems. Completion of the specific aims and training objectives in this proposal will advance my training in biochemistry and structural biology, while also providing new mechanistic insights that clarify how CRISPR systems limit viral spread through a population by triggering cell death through a multipronged attack on translation.

PI_NAMEs: BURMAN, NATHANIEL  (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: Adaptive Immune System;Affinity;anti-toxin;Archaea;Bacteria;Bacteriophages;Binding;Biochemical;Biochemistry;Biological;Biological Assay;Biological Process;career;Cell Aging;Cell Death;Chimeric Proteins;Coenzyme A;Collaborations;Complex;Computing Methodologies;Conflict (Psychology);Cryoelectron Microscopy;Defense Mechanisms;Detection;Development;DNA;DNA cassette;ds-DNA;Elements;EMSA;endonuclease;experimental study;Family;Fellowship;Fusion Toxin;Gene Proteins;Genes;Genetic;Guide RNA;Immune;Immune response;Immune signaling;Immune system;In Vitro;Incubated;Infection;insight;Invaded;Link;Mass Spectrum Analysis;Measures;Mediating;Memory;Messenger RNA;Molecular;Molecular Conformation;novel;Nucleic Acids;oligoadenylate;Other Genetics;Parasites;Periodicity;Phylogenetic Analysis;Planet Earth;Polymerase;Population;Predatory Behavior;Productivity;Protein Biosynthesis;Proteins;public database;Radiolabeled;Research;Research Personnel;Resolution;response;Ribonucleoproteins;Ribosomes;RNA;RNA Binding;Scientist;Signal Transduction;Signaling Molecule;skills;structural biology;Structure;System;Testing;Toxin;Training;Transcript;Transfer RNA;translation assay;Translational Repression;Translations;Viral;Virus;Virus Diseases;virus genetics;Virus Replication;Work

PROJECT_TITLE: CRISPR RNA-guided recognition of invading RNA activates a multipronged cell death response

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F04-S (20)]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurosciences;Pediatric;Post-Traumatic Stress Disorder (PTSD);Sleep Research

PHR: Study Title: Sleep and emotion processing in adolescent Post-traumatic stress Disorder Principal Investigators: Stephanie Jones, PhD and Ryan Herringa, MD, PhD Project Narrative Despite clear links between sleep and the progression and maintenance of post-traumatic stress disorder (PTSD), research using objective assessments of sleep during adolescence, when PTSD incidence rises markedly, are nearly absent. In this work, we will use sophisticated technologies to objectively record the brain during sleep, in the laboratory and in the home environment, and will explore sleep’s relationship to emotional learning (in the laboratory) and daily affective function and symptom severity (longitudinally in the home). Finally, we will test whether we can reliably increase the deepest stage of sleep using a novel sleep-wearable headband that employs auditory stimulation algorithms to enhance deep sleep and represents the first validated, non-pharmacological method available for sleep enhancement. The results of this work promise to have a significant impact on our understanding of sleep’s role in the pathophysiology of adolescent PTSD, and to lay the groundwork for larger clinical trials of sleep neuromodulatory interventions.

PI_NAMEs: HERRINGA, RYAN J;JONES, STEPHANIE  (contact)

PROGRAM_OFFICER_NAME: BORJA, SUSAN EILEEN

PROJECT_TERMS: Acoustic Stimulation;Acoustics;Acute;Adolescence;Adolescent;Affect;Affective;Age;Algorithms;associated symptom;Behavioral;Brain;Clinical Trials;Cognitive;comorbidity;Data;density;design;Development;Devices;Disease;Doctor of Philosophy;Early Intervention;effectiveness evaluation;Electroencephalography;emotion regulation;Emotional;Emotions;Equilibrium;experience;Failure;Frequencies;Functional disorder;Functional impairment;Goals;habituation;Home;Home environment;Hour;Impairment;improved;Incidence;Interpersonal Violence;Intervention;Laboratories;Learning;life span;Light;Link;Maintenance;Measures;Mediating;Memory;Memory impairment;Methodology;Methods;Mood Disorders;negative affect;Negative Valence;neural;neuroregulation;non rapid eye movement;novel;novel marker;Pathology;Phenotype;Play;Post-Traumatic Stress Disorders;predicting response;Prefrontal Cortex;Principal Investigator;reduce symptoms;Regulation;Reinforcing Factor;Research;response;Risk;Role;Sensitivity and Specificity;Severities;Sleep;Sleep Deprivation;Sleep disturbances;sleep quality;Sleep Stages;Stimulus;Structure;Substance abuse problem;suicidal;Symptoms;Synapses;System;Technology;Testing;Time;Trauma;trauma exposure;traumatic event;United States;Variant;wearable device;Work;Youth

STUDY_SECTION: MESH

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


ED_INST_TYPE: GRADUATE SCHOOLS

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: Project Narrative The surface of the intestine is the largest area of the body exposed to microbes, which in turn constantly affect host physiology. The gut contains as many neurons as the spinal cord and more immune cells than all other compartments combined. The goal of this project is to pinpoint the host and microbial components that play a role in the maintenance and recovery of enteric neurons post infection or antibiotic treatment, generating knowledge relevant to several chronic inflammatory disorders of the intestine and other tissues.

PI_NAMEs: MUCIDA, DANIEL S (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Affect;Afferent Neurons;age related changes;Antibiotic Therapy;Area;Cell Death;cell dedifferentiation;Cell Nucleus;Cells;Chronic;Collection;Cues;Data;dietary;dysbiosis;Enteral;enteric infection;Equilibrium;experience;Exposure to;Face;Functional Gastrointestinal Disorders;Funding;gain of function;gastrointestinal;gastrointestinal function;Gastrointestinal tract structure;Gene Expression;Genetic;Genetic study;Glial Differentiation;gliogenesis;Gnotobiotic;Goals;gut microbiota;Image;Immune;Induced Neurons;Infection;Inflammasome;Inflammation;Inflammatory Bowel Diseases;Injury;Interneurons;Intestines;Invaded;Investigation;Knowledge;Ligands;loss of function;Maintenance;Maps;Mediating;metabolomics;Microbe;microbial;microbiota;microbiota transplantation;microorganism antigen;Molecular;Motor Neurons;Mus;neurogenesis;Neuroglia;Neuroimmune;neuron component;neuron loss;neuron regeneration;Neuronal Differentiation;Neurons;novel;pathogen;Pathway interactions;Pattern;Physiological;Physiology;Population;prevent;Process;reconstitution;Recovery;Resistance;response;Role;secondary infection;Signal Induction;Signal Transduction;Spinal Cord;Surface;Tissues;tool;transcriptomics;transdifferentiation

PROJECT_TITLE: Neuro-immune interactions at the intestinal surface

STUDY_SECTION: DNPD

STUDY_SECTION_NAME: Digestive and Nutrient Physiology and Diseases Study Section [DNPD]


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

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE As neurodegenerative diseases, including Alzheimer’s disease and Related Dementias, are increasingly prevalent in our aging society, it is imperative that we understand the basic biological mechanisms that underlie these diseases in order to generate effective treatments. This project investigates the regulation of neuronal autophagy, a mechanism that neurons utilize to maintain their overall health and function but decreases with age. The successful completion of this project will extend our knowledge of neuronal autophagy and its connection to neurodegeneration, allowing for the formulation of more effective therapeutic agents.

PI_NAMEs: TSONG, HEATHER  (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: Affect;Age;age related neurodegeneration;aged;Aging;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease related dementia;Animal Model;Autophagocytosis;Autophagosome;Biogenesis;Biological;Biological Assay;Biological Models;Caenorhabditis elegans;career;Cell division;Cells;Co-Immunoprecipitations;Communication;confocal imaging;CRISPR/Cas technology;Critical Thinking;Data;Disease;disease model;disease phenotype;Down-Regulation;Educational workshop;effective therapy;Environment;experimental study;Formulation;Genes;Genetic;Health;Homeostasis;Homologous Protein;Human;In Vitro;in vivo;Institution;Instruction;Knock-out;Knowledge;Lysosomes;Medical center;Mentorship;Metabolic;mimetics;Mitotic;Modeling;Mus;mutant;Nerve Degeneration;Nervous System;Neurobiology;Neurodegenerative Disorders;Neurons;new therapeutic target;null mutation;Optics;overexpression;Pathogenesis;Pathway interactions;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphorylation Site;Phosphotransferases;Physiological;postmitotic;prediction algorithm;Protein Dephosphorylation;Proteins;Quality Control;Recycling;Regulation;Research;Review Literature;Role;Science;Serine;Site;skills;Societies;symposium;Therapeutic;Therapeutic Agents;therapeutically effective;Training;Up-Regulation;wasting;Western Blotting

PROJECT_TITLE: WIPI2B/ATG-18 phosphorylation regulates neuronal autophagosome biogenesis in vivo

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03C-N (20)]


NIH_SPENDING_CATS: Neurosciences

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE Establishing specific synaptic connections is critical for proper neural circuit function, and alterations in connectivity have been linked to neurological diseases such as Alzheimer’s and Parkinson’s diseases. This proposal will investigate how two subfamilies of cell surface proteins, the Dprs and DIPs, instruct specific connectivity in Drosophila central motor circuits. This study will also examine the signaling mechanisms underlying Dpr and DIP interactions, and potentially provide new signaling insights into their vertebrate orthologs, the IgLONs, which are associated with various neurological diseases.

PI_NAMEs: ZHANG, RUILING  (contact)

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Alzheimer's Disease;Animal Behavior;Attention;autism spectrum disorder;Axon;axonal pathfinding;Biochemical;Biochemistry;Bioinformatics;Biotinylation;candidate validation;Cell Adhesion Molecules;Cell membrane;Cell Surface Proteins;Cell Survival;cellular transduction;Central Nervous System;Cognition;Communication;Complex;Data;Defect;Dendrites;Development;Disease;Dorsal;Drosophila genus;Electrophysiology (science);Embryo;Engineering;Ensure;Environment;fly;functional outcomes;Growth;Horseradish Peroxidase;Immunoglobulin Domain;Immunoglobulins;innovation;insight;Integral Membrane Protein;Interneurons;Knowledge;Label;Link;Mass Spectrum Analysis;member;Membrane;Microscopy;Molecular;Morphology;Motor;Motor Neurons;Muscle;mutant;Nerve;nerve supply;nervous system development;Nervous System Disorder;neural circuit;neuromuscular;neuronal circuitry;Neurons;novel;optogenetics;Organism;Orthologous Gene;Parkinson Disease;presynaptic;Presynaptic Terminals;Process;Proteins;Proteomics;receptor;Role;Schizophrenia;Signal Pathway;Signal Transduction;Specific qualifier value;Specificity;Synapses;System;Testing;Variant;Visual;Work

PROJECT_TITLE: Uncovering DIP-α signaling pathways underlying circuit assembly

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03A-E (20)]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cardiovascular;Heart Disease;Mental Health;Neurosciences;Women's Health Research

ORG_CITY: FORT COLLINS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: Project Narrative Cardiovascular diseases are the leading cause of death globally and chronic stress is a well-known risk factor for cardiovascular pathologies. Additionally, women have increased risk of stress-related cardiovascular disease; however, the neurobiological mechanisms underlying this increased risk are not well understood. Therefore, this proposal seeks to determine neural circuit-specific adaptations induced by stress that lead to differential cardiovascular susceptibility in males and females.

PI_NAMEs: BOUCHET, COURTNEY ANNE (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: acute stress;Anatomy;Animals;Architecture;arterial stiffness;arteriole;biological adaptation to stress;Blood Pressure;blood pressure elevation;Blood Vessels;Brodmann's area;Cardiovascular Diseases;cardiovascular effects;cardiovascular health;Cardiovascular Pathology;Cardiovascular Physiology;cardiovascular risk factor;Cardiovascular system;career;career development;Cause of Death;cell type;Chronic;Chronic stress;comorbidity;Data;Deep Brain Stimulation;Dimensions;Electrophysiology (science);Endothelium;Ensure;excitatory neuron;experimental study;Fellowship;Female;gamma-Aminobutyric Acid;Genetic Transcription;Glutamates;Heart Rate;Human;Hypothalamic structure;Impairment;in vivo;Incidence;inhibitory neuron;knock-down;knowledge base;Laboratories;Learning;Link;male;Mediating;Mental Depression;Mentors;Mentorship;Microvascular Dysfunction;Mood Disorders;Myography;neural circuit;Neuroanatomy;neurobiological mechanism;Neuronal Plasticity;Neurons;Neurosecretory Systems;optogenetics;Outcome;Output;paraventricular nucleus;Pathology;pharmacologic;Pharmacology Study;Physiologic pulse;Physiological;Postdoctoral Fellow;Posterior Hypothalamus;postsynaptic;Predictive Factor;Predisposition;Prefrontal Cortex;pressure;presynaptic;prevent;programs;Psychosocial Stress;Rattus;Reporting;Research;resilience;Resistance;response;restraint;Risk;Role;Running;sex;Sex Differences;Signal Transduction;skills;Slice;Stress;Synapses;Synaptic plasticity;Tachycardia;Testing;Training;Transgenic Organisms;Translating;Vascular Diseases;Viral;Woman;Women's prevalence;Work

PROJECT_TITLE: Cortical-hypothalamic control of the cardiovascular consequences of stress


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

ORG_CITY: SAINT LOUIS

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative. Oxidative imbalance and functional impairment of mitochondria mediates pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD) and its related disorders (ADRDs). Although mitochondria are among the prominent intracellular site for ROS generation, standard clinical 18F-FDG PET/CT lacks sensitivity and diagnostic robustness. Furthermore, the mechanism of its retention and trapping poorly correlates with oxidative imbalance. To address this critical unmet need, this project is focused on biochemical validation of a novel redox-sensitive molecular PET imaging probe (identified as 18F-SLN-128) in Huntington’s disease and AD transgenic mice models, GMP production to obtain regulatory approval (eIND from FDA) including institutional RDRC, IRB approvals, and human dosimetry studies as well as assessment in AD participants for objective of its translation from the bench into clinical nuclear medicine for healthcare management. Successful accomplishment of proposed aims could deliver a redox-sensitive PET molecular imaging agent for stratification of therapeutic choices or alterations in lifestyles for managing ROS-mediated mitochondrial dysfunction in neurodegenerative diseases in general, and AD and ADRDs in particular.

PI_NAMEs: BENZINGER, TAMMIE LEE SMITH;SHARMA, VIJAY  (contact)

PROGRAM_OFFICER_NAME: ROVESCALLI, ALESSANDRA C

PROJECT_TERMS: 3-nitropropionic acid;4 hydroxynonenal;abeta deposition;AD transgenic mice;Address;Aducanumab;Age;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid;Amyloid beta-Protein;Amyotrophic Lateral Sclerosis;APP-PS1;Authorization documentation;base;Biochemical;Biodistribution;Biological;Biological Markers;biomarker evaluation;Brain;Brain imaging;Brain region;Cardiovascular system;Cell Culture Techniques;Cells;Characteristics;Chemistry;Chronic;circulating biomarkers;Classification;Clinical;Clinical Data;cohort;Complex;Corpus striatum structure;Cysteine;Data;Data Correlations;Deposition;design;Development;Diagnosis;Diagnostic;Discipline of Nuclear Medicine;Disease;Dose;dosimetry;Drug Kinetics;Encephalitis;Etiology;Excretory function;FDA approved;first-in-human;fluorescence imaging;fluorodeoxyglucose;Free Radicals;Functional disorder;Functional Imaging;Functional impairment;Generations;glial activation;Glioblastoma;glucose metabolism;health management;Human;Huntington Disease;Image;imaging agent;Imaging Device;imaging probe;Impairment;in vivo;Inflammation;Injections;Innate Immune System;Institution;Institutional Review Boards;intravenous injection;kinetic model;Life Style;Lipid Peroxidation;Location;longitudinal analysis;Macaca mulatta;manufacture;Mediating;Messenger RNA;Microglia;misfolded protein;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Modeling;Modification;Mole the mammal;Molecular;molecular imaging;Monoclonal Antibody Therapy;mouse model;Multiple Sclerosis;Mus;Muscular Dystrophies;nano;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;Neurons;nitration;non-invasive imaging;nonhuman primate;novel;Nuclear;Nucleic Acids;Organ;Outcome;Output;Oxidants;oxidation;Oxidation-Reduction;Parkinson Disease;Participant;Pathogenesis;Patients;Penetration;Peripheral;PET/CT scan;Pilot Projects;Population;Positron-Emission Tomography;preclinical imaging;Production;protein aggregation;protein misfolding;Proteins;Qualifying;quantitative imaging;Radiometry;Radiopharmaceuticals;radiotracer;rational design;Reporting;Role;Running;Safety;Saline;Scanning;Senile Plaques;side effect;Site;standard of care;Stroke;Structure-Activity Relationship;Superoxides;Synapses;systemic inflammatory response;tau Proteins;tau-1;Techniques;Therapeutic;Therapeutic Intervention;Time;Tissues;Toxicology;Toxin;Tracer;Translations;Traumatic Brain Injury;Treatment Efficacy;treatment stratification;uptake;Validation;Venous;X-Ray Computed Tomography

PROJECT_TITLE: Development of PET Tracer for Imaging Brain Inflammation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MCST-U (81)]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative Precise patterns of connectivity within and across brain regions drive the perception of visual stimuli — disrup- tion of these patterns underlie a number of complex psychiatric and neurological diseases. Important advances have elucidated neural architectures within single brain regions, but neural connectivity across brain regions is still deeply understudied, particularly in an intact animal. This proposal leverages a breakthrough two-photon holographic mesoscope — that can uniquely record and manipulate individual neurons across brain regions — to causally interrogate how interareal neural connections govern the cortical computations supporting perception.

PI_NAMEs: SIT, KEVIN KA-MAN (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Animals;Architecture;Area;area striata;Attenuated;attenuation;Behavioral;Brain;Brain region;Cells;Complex;Dependence;Dissection;Elements;excitatory neuron;experimental study;extrastriate visual cortex;Feedback;Holography;Image;improved;in vivo;Individual;Interneurons;Maps;Mediating;Mediator;Mental disorders;Microscope;Modeling;multi-photon;Mus;Nervous System Disorder;neural;neural circuit;neural correlate;Neurons;Neurosciences;novel;Optics;optogenetics;orientation selectivity;Pattern;Perception;Phase;Population;Process;Property;receptive field;response;Role;Sensory;sensory input;Somatostatin;Stimulus;stimulus processing;Synapses;Techniques;Testing;Time;two-photon;V1 neuron;Vision;Visual;Visual Perception;visual processing;visual stimulus;Visual System;Work

PROJECT_TITLE: Contributions of cortical feedback to orientation-dependent surround suppression

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02B-Y (20)]


NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Nutrition;Obesity

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

PHR: PROJECT NARRATIVE Nearly 1 in 3 people are overweight and nearly 2 in 5 people have obesity; so, obesity is a national epidemic. The proposed research is highly relevant to public health because new effective therapies for obesity and obesity-related complications (e.g., NAFLD/NASH and type 2 diabetes) are needed. The tools and knowledge gained, and the mechanistic details to be discovered in this proposal, all fit the purview of NIDDK's mission to reduce the burden of obesity and obesity-related metabolic complications.

PI_NAMEs: HUANG, WENDONG  (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: Adipose tissue;Adult;Affinity;Applications Grants;Bile Acids;Binding;Biochemical;Biological Assay;Body Weight decreased;candidate identification;Cell Line;Cell Physiology;Classification;Clinical;Coupled;CYP8B1 gene;Cytochrome P450;Detection;diabetic;diet-induced obesity;disease model;drug candidate;drug development;effective therapy;Energy Metabolism;Enzymes;Epidemic;Family;Fatty Liver;fecal transplantation;glucose metabolism;Goals;GPBAR1 gene;Growth;GTP-Binding Proteins;gut microbiome;Hepatocyte;high throughput screening;Human;hydrophilicity;Hydroxylation;improved;in vivo;Inflammation;inhibitor;inhibitor therapy;innovation;insulin sensitivity;intestinal barrier;Intestines;knock-down;Knock-out;Knockout Mice;Knowledge;Lead;lead candidate;Libraries;lipid metabolism;Liver;Mediating;Metabolic;Metabolic Diseases;Methods;Mission;Modeling;mortality;mouse model;Mus;National Institute of Diabetes and Digestive and Kidney Diseases;Non obese;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;Obesity;obesity treatment;Outcome;Overweight;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacologic Substance;Play;polypeptide;Production;Property;Proteins;Public Health;Quality of life;receptor;Research;Role;Safety;side effect;Signal Pathway;Signal Transduction;Structure;Structure-Activity Relationship;Testing;Therapeutic Effect;therapeutic target;tool;treatment effect;United States Food and Drug Administration;Validation;Wild Type Mouse

PROJECT_TITLE: Targeting bile acid composition to treat metabolic diseases

STUDY_SECTION: CSME

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


ORG_CITY: IOWA CITY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE The goal of this project is to understand how the mitochondrial dicarboxylate carrier regulates liver gluconeogenic metabolism in normal and type 2 diabetes states. Dysregulated liver metabolism contributes to type 2 diabetes and many other diseases. This project will provide a framework to better understand and potentially treat these diseases.

PI_NAMEs: TAYLOR, ERIC B (contact)

PROJECT_TERMS: Address;Alanine;Amino Acids;Articulation;Attention;Attenuated;Automobile Driving;Biochemical;Biological Assay;Carbon;Cell Culture System;Citric Acid Cycle;Complex;Cytosol;Data;dicarboxylate-binding protein;Diet;Disease;euglycemia;Fasting;Fatty acid glycerol esters;feeding;Feeds;Functional disorder;gain of function;Genetic;Genetic Transcription;Gluconeogenesis;Glucose;Glutamine;Goals;Hepatic;hepatic gluconeogenesis;Hormonal;in vivo;in vivo evaluation;innovation;Insulin Resistance;Knock-out;Left;Link;Liver;liver metabolism;loss of function;Luciferases;Malates;Metabolic;Metabolism;metabolomics;Mitochondria;mitochondrial metabolism;Modeling;Molecular;mouse genetics;Mus;NADH;Non-Insulin-Dependent Diabetes Mellitus;novel;Nutritional;overexpression;Pathway interactions;Peripheral;Physiology;Play;Primary Cell Cultures;Process;Proteomics;Pyruvate;Recommendation;Recycling;Regulation;Reporter;Research;Role;stable isotope;Sucrose;System;Testing;Text;Tissues;Transport Process

PROJECT_TITLE: Regulation of Hepatic Fuel Fluxes by the Mitochondrial Dicarboxylate Carrier

STUDY_SECTION: POMD

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


NIH_SPENDING_CATS: Biotechnology

ORG_DEPT: CHEMISTRY

PHR: Project Narrative: This project aims to develop a new methodology for the site- and stereoselective formation of C–C bond from C–H bonds through the use of a photocatalytically active uranyl-containing artificial metalloenzyme. Through directed evolution using techniques such as site-saturation mutagenesis, artificial metalloenzymes containing non-native, uranyl cofactors will be developed to catalyze asymmetric chemical reactions with high activity and high selectivity. This will create new approaches by which molecules relevant to human health can be synthesized by new classes of selective C–H bond functionalization.

PI_NAMEs: HERRERA, GABRIEL  (contact)

PROJECT_TITLE: Artificial Metalloenzymes Containing Uranyl Cofactors for Photocatalytic C-H Bond Functionalization


NIH_SPENDING_CATS: Genetics

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE The discovery of human riboswitches represents a new layer of gene regulation that will aid researchers in better understanding how cells respond to metabolites in their environments. This may include previously unknown regulatory events and signaling molecules dictating nuanced cell behaviors, non-coding genetic variations contributing to diseased and healthy phenotypes, and insights into our molecular evolutionary heritage. In essence, eukaryotic riboswitches could teach us to speak the language of a cell more fluently, enabling the discovery of therapeutic targets for dysfunctional cellular systems.

PI_NAMEs: SKABELUND, RACHEL ANNE (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: 5' Untranslated Regions;Address;Algorithms;Animals;aptamer;Bacteria;Binding;Binding Sites;Biological Assay;Calorimetry;cell behavior;Cell Line;Cells;Cellular Assay;Communities;Complex;complex IV;Cyclic AMP;cytochrome c oxidase;Data;Dedications;Detection;Dialysis procedure;dimethyl sulfate;Disease;disease phenotype;Educational process of instructing;Electron Transport;Environment;Enzymes;Equilibrium;Event;Forskolin;fungus;Future;Gene Expression;Gene Expression Regulation;Genetic Variation;Genus Hippocampus;high throughput screening;Human;human disease;in silico;In Vitro;in vivo;Incubated;Individual;insight;Interdisciplinary Study;Investigation;Knock-out;Language;Length;Libraries;Ligands;Literature;Location;Luciferases;Mass Spectrum Analysis;Measures;Messenger RNA;Metabolic;metabolic abnormality assessment;Metabolism;Metabolite Interaction;Methods;Microphthalmos;Mitochondria;Molecular;Molecular Conformation;Mutation;novel;Organism;overexpression;Oxidases;Oxidative Phosphorylation;Peripheral;Phenotype;Phosphorylation;Plants;Polyacrylamide Gel Electrophoresis;polyadenylated messenger RNA;Production;Reactive Oxygen Species;Regulation;Regulatory Pathway;Reporter;Research Personnel;Respiration;respiratory;response;ribosome profiling;RNA;RNA Biochemistry;Role;Scientist;screening;Signaling Molecule;skills;skin lesion;small molecule;Structure;System;Techniques;Testing;therapeutic target;Thiamine Pyrophosphate;Tissues;Titrations;Training;Transcript;translation assay;Translations;Universities;Untranslated RNA;Utah;Western Blotting

PROJECT_TITLE: Human COX7B Contains a cAMP-Responsive Riboswitch that Modulates Oxidative Phosphorylation


ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: NARRATIVE Mitochondria are energy-producing components within our cells, and perturbations in their function are implicated in a wide range of human diseases, including neurodegenerative diseases such as Alzheimer's and Parkinson's, cardiovascular disorders, metabolic disorders, and cancer. I will investigate how one of the important proteins critical for mitochondrial health, YME1, makes molecular decisions about how it processes substrates in response to cellular stress and toxicity, using integrated structural, biochemical, and computational approaches.

PI_NAMEs: ALEXANDRESCU, LAUREN  (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: activation-induced cytidine deaminase;age related;Alzheimer's Disease;Apoptosis;ATP-Dependent Proteases;Automobile Driving;base;Binding;Biochemical;Biological Assay;Cardiovascular Diseases;Catalytic Domain;Cells;Cellular biology;Cellular Stress;Communication;Complex;Consensus Sequence;Conserved Sequence;Cryoelectron Microscopy;Decision Making;Enzymes;Event;Eye diseases;Fluorescence;functional plasticity;Genetic;Health;Homeostasis;Human;human disease;Impairment;Inner mitochondrial membrane;insight;Investigation;Malignant Neoplasms;Mediating;Metabolic;Metabolic Diseases;migration;Mitochondria;mitochondrial dysfunction;Mitochondrial Proteins;Modality;Modeling;Molecular;Molecular Chaperones;molecular dynamics;molecular modeling;Morphology;Mutagenesis;N-terminal;Neurodegenerative Disorders;Optic Atrophy;Optic atrophy 1;Organelles;Outcome Study;Oxidative Phosphorylation;Parkinson Disease;Pathologic;Peptide Hydrolases;Peptides;Physiological;Play;preference;preservation;prevent;Process;protein aggregation;protein function;Protein Isoforms;Proteins;Proteolytic Processing;Proteome;proteostasis;Quality Control;Regulation of Proteolysis;response;Role;Site;Stimulus;Stress;Structure;Tail;Testing;Toxic effect;Work;Yeasts

PROJECT_TITLE: Investigating the mechanism of decision-making in the mitochondrial Protease YME1


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

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: NARRATIVE Human genetic studies have revealed robust links between epigenetic regulators and complex disorders, such as autism, schizophrenia and obsessive compulsive disorder, but knowledge of the mechanistic basis of these links continues to elude us. Here, we seek to understand the impact of mutations in the risk candidate gene Chd8 on cerebellum-specific neuropathology. This work will offer insights into novel causal contributions of Chd8 and cerebellar circuits to high-order non-motor functions and complex mental health disorders, inform future biomarker development, and can ultimately reveal new molecular and circuit targets for intervention.

PI_NAMEs: FIORAVANTE, DIASYNOU  (contact);NORD, ALEXANDER

PROGRAM_OFFICER_NAME: LEINWAND, SARAH GOLDBERG

PROJECT_TERMS: Ablation;Adolescent;Adult;Affective;Animals;Anxiety;associated symptom;autism spectrum disorder;Behavior;behavior test;Behavioral;Biological Process;biomarker development;Brain;Brain region;Candidate Disease Gene;Cell Nucleus;Cells;Cerebellar Nuclei;Cerebellum;Cerebral cortex;Chromatin;Code;Cognitive;cohort;Common Core;Communication;Complex;de novo mutation;Dependovirus;Development;Dimensions;Disease;Dissociation;effective therapy;Electrophysiology (science);Emotional;endophenotype;Enterobacteria phage P1 Cre recombinase;Epigenetic Process;Essential Genes;Etiology;Event;Exhibits;experimental study;Extinction;Frequencies;Functional disorder;Future;Genes;Genetic;Genetic Risk;Genetic study;Genetic Transcription;Genomics;Heterozygote;Hippocampus;Human;Human Genetics;improved;in vivo;Injections;insight;Intervention;Knowledge;Laboratories;Learning;learning extinction;Limbic System;Link;LoxP-flanked allele;Memory;Mental disorders;Modeling;Molecular;molecular pathology;Molecular Profiling;Motor;motor control;mouse model;Mus;mutant;Mutation;mutation carrier;Nervous System Disorder;neural circuit;neural network;Neurobiology;Neurodevelopmental Disorder;Neurons;neuropathology;neurophysiology;neuropsychiatric disorder;new therapeutic target;novel;Obsessive-Compulsive Disorder;optogenetics;Output;Pathology;Pathway interactions;Phenotype;prenatal;Property;Prosencephalon;Proteins;Purkinje Cells;Regulation;Reporting;Research;Rest;Risk;Risk Factors;risk sharing;risk variant;Role;Schizophrenia;Signal Transduction;single nucleus RNA-sequencing;social;Social Behavior;Symptoms;Synapses;Testing;Thalamic Nuclei;therapy outcome;Time;Transcriptional Regulation;transcriptomics;Work

PROJECT_TITLE: Chd8-dependent molecular and functional vulnerabilities in developed cerebellar limbic circuits

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BN-P (57)]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

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

ORG_CITY: SANTA BARBARA

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA BARBARA

PHR: PROJECT NARRATIVE Despite its importance to the formation of the body plan, little is known about the mechanisms driving primate gastrulation. We aim to create a high-throughput, three-dimensional model of the peri-implantation primate embryo using chimpanzee induced pluripotent stem cells (iPSCs) encapsulated in hydrogel droplets. By using a microfluidic droplet sorter to control the number of cells and cell types in each droplet, we will investigate the impact of cell number, cell type, and local tissue mechanics on model embryo structure and explore the role of morphogen signaling dynamics on cell fate decisions via downstream optogenetic stimulation.

PI_NAMEs: RUFO, JOSEPH  (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: 3-Dimensional;Address;Animal Model;Anterior;Automobile Driving;Biocompatible Materials;biomaterial compatibility;Birth;Black Box;Cell Count;Cell Culture Techniques;Cell Differentiation process;cell type;Cells;Communicable Diseases;Complex;cost;Development;Devices;Embryo;embryo quality;embryo tissue;Embryonic Development;Embryonic Structures;Encapsulated;Endoderm;Engineering;Epiblast;Ethics;Failure;Fertilization;Fertilization in Vitro;gastrulation;Germ Layers;Heterogeneity;histological specimens;Human;Human Development;Hydrogels;Implant;implantation;In Vitro;in vitro Model;Individual;induced pluripotent stem cell;infertility treatment;insight;interest;Investigation;Light;Maps;Maternal-Fetal Exchange;Mechanics;Methods;Microfluidics;migration;Modeling;Molecular;Morphogenesis;morphogens;Morphology;mouse model;nonhuman primate;novel;novel therapeutics;Optics;optogenetics;Pan Genus;Pathogenesis;Pattern;Phenotype;Play;Postnidation Embryo Development;Pregnancy;prevent;primate development;Primates;Process;Property;Reproducibility;Research;Research Personnel;Role;screening;self assembly;self organization;Signal Pathway;Signal Transduction;spatiotemporal;stem cell model;stem cells;Structure;three dimensional structure;three-dimensional modeling;Time;Tissues;tool;Toxic effect;Uterus;Variant;WNT Signaling Pathway

PROJECT_TITLE: Shining light on the mechanisms of primate gastrulation:  development of high-throughput, optogenetic tools for understanding embryonic development

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


NIH_SPENDING_CATS: Nutrition;Obesity;Precision Medicine

ORG_CITY: SILVERTHORNE

ORG_NAME: KEYSTONE SYMPOSIA

PHR: PROJECT NARRATIVE Obesity and its metabolic consequences are associated with increased mortality and morbidity because of their links to Type 2 diabetes (T2D), cardiovascular, lung, gastrointestinal, osteoarticular and reproductive diseases. This Keystone Symposia conference will explore the latest in the causes of obesity, as well as how the heterogeneity of obesity impacts precision management. The conference will bring together an interdisciplinary group of investigators who research obesity and cardiometabolic disease in order to network and develop new collaborations to improve health outcomes.

PI_NAMEs: SHEPPARD, TERRY L. (contact)

PROGRAM_OFFICER_NAME: HALES, CRAIG MAURICE

PROJECT_TERMS: Address;Adopted;Affect;Area;Big Data;British Columbia;burden of illness;Canada;Cardiometabolic Disease;Cardiovascular Diseases;Cardiovascular system;career development;clinical implementation;clinical practice;Collaborations;Communities;comorbidity;Computational Technique;design;Dyslipidemias;Educational workshop;Electronic Medical Records and Genomics Network;Environment;Environmental Impact;ethnic diversity;Future;gastrointestinal;Genetic;Health;Heterogeneity;Human;Hypothalamic dysfunction;improved;Industrialization;innovation;Innovative Therapy;interest;International;Joints;Kidney Diseases;Knowledge;Learning;Link;Liver diseases;Lung;member;Metabolic;Methodology;model organism;Modeling;Molecular Target;Morbidity - disease rate;mortality;multidisciplinary;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;Obesity;obesity management;Outcome;Participant;personalized management;Population;posters;precision medicine;Prevalence;programs;reproductive system disorder;Research;Research Personnel;Role;Scientist;Speed;symposium;Technology;Touch sensation;Translations;Work

PROJECT_TITLE: Obesity: Causes and Consequences

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-7 (O3)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Biodefense and Related Countermeasures;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Dementia;Disability Research;Emerging Infectious Diseases;Infectious Diseases;Neurodegenerative;Neurosciences;Physical Activity;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE After acute COVID-19 infection, millions of patients, both old and young, suffer from a syndrome called Long COVID, which can include months and years of brain dysfunction even after mild infections, placing patients at risk for both “Alzheimer’s disease and/or related dementias” (ADRD) and profound physical disability. Growing evidence indicates that Long COVID’s debilitating brain and body disease is often due to persistent inflammation and new problems of our immune system, but anti-inflammatory or immunomodulator medications have not been adequately studied in patients with Long COVID. The Randomized trial EValuating Baricitinib on pERSistent nEurologic and Cardiopulmonary Symptoms of Long COVID (REVERSE-LC) clinical investigation will enroll 500 patients with Long COVID to determine if baricitinib—an anti-inflammatory and immunomodulator drug that is FDA-approved to save lives in acute COVID-19—improves brain function and physical impairment in patients suffering from Long COVID.

PI_NAMEs: ELY, E WESLEY (contact);HSUE, PRISCILLA Y.;MARCONI, VINCENT CHARLES

PROGRAM_OFFICER_NAME: RYAN, LAURIE M

PROJECT_TERMS: 2019-nCoV;acute COVID-19;Acute-Phase Proteins;Address;Adult;Affect;Aftercare;age acceleration;Age related comorbidities;aging brain;Alzheimer's disease related dementia;Alzheimer's disease risk;Anti-Inflammatory Agents;Automobile Driving;Biological Markers;Brain;Brain Diseases;brain dysfunction;Cardiopulmonary;Caring;Central Nervous System;Cerebrospinal Fluid;Cessation of life;Chronic;chronic autoimmune disease;Clinical;clinical investigation;Clinical Trials;Cognition;Cognitive;cognitive disability;cognitive function;COVID-19;COVID-19 sequelae;cytokine;Data;data management;Defect;dementia risk;Development;disability;Disease;Double-Blind Method;Early treatment;effective intervention;effective therapy;Enrollment;epidemiology study;executive function;exercise capacity;exercise intolerance;Exercise Test;experience;Family;FDA approved;fitness;follow-up;Follow-Up Studies;functional disability;Functional disorder;functional status;Funding;Future;Granulocyte-Macrophage Colony-Stimulating Factor;high risk;Image;Immune;immune modulating agents;Immune system;Immune Targeting;Immunologic Markers;Immunomodulators;immunoregulation;Impaired cognition;Impairment;improved;indexing;industry partner;Infection;Inflammation;Inflammation Mediators;Inflammatory;inflammatory marker;Infrastructure;inhibitor;Injury;innovation;insight;Interferons;Interleukin-6;Intervention;Investigation;JAK1 gene;JAK2 gene;Janus kinase;Laboratories;Lead;Left;Life;Link;Long COVID;Measures;Mediating;Memory;Mental Health;mild cognitive impairment;Molecular;Neurobehavioral Manifestations;Neurocognitive;Neuroglia;neuroimaging;neuroinflammation;Neurologic;neuron loss;Neuropsychology;Neurotoxins;novel;Oral;Outcome;Participant;Pathogenesis;Pathologic;Pathway interactions;Patient Self-Report;Patients;Persons;Pharmaceutical Preparations;Pharmacy facility;Physical Exercise;Physical Fitness;Physical Function;physical impairment;physical symptom;physically handicapped;Placebos;Plasma;Protocols documentation;Public Health;Pulmonary Heart Disease;Quality of life;randomized placebo controlled trial;randomized placebo-controlled clinical trial;randomized trial;Reporting;Rheumatoid Arthritis;Risk;Safety;SARS-CoV-2 infection;Science;Severity of illness;Signal Transduction;Site;Specimen Handling;Survivors;Symptoms;Syndrome;System;Testing;TNF gene;treatment effect;United States;Vaccines;Visit;Work

PROJECT_TITLE: REVERSE-Long COVID: A Multicenter Randomized, Placebo-Controlled Clinical Trial of Immunomodulation (with Baricitinib) for Long COVID Related ADRD

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ED_INST_TYPE: UNIVERSITY-WIDE

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

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Project Narrative Liver disease is a multifaceted condition in which multiple etiologies converge towards a common inflammatory phenotype, with nonalcoholic fatty liver disease (NAFLD) emerging as one of the leading etiologies as it affects nearly 25% of the global population. Nearly half of these patients will advance towards the inflammatory subtype(NASH) and even on to carcinogenesis, making it crucial to characterize the way in which hepatic steatosis induces inflammation in this transition from NAFLD to NASH to better improve patient outcomes. In this proposal, we aim to focus on AKT regulation of hepatic bioactive lipid metabolism and its role on macrophage chemotaxis and polarization to promote chronic inflammation in liver disease.

PI_NAMEs: ALBA, MARIO  (contact)

PROGRAM_OFFICER_NAME: RIVERS, ROBERT C

PROJECT_TERMS: Address;Affect;AKT Signaling Pathway;AKT1 gene;AKT2 gene;ALOX15 gene;Anabolism;angiogenesis;Animal Disease Models;Attenuated;Automobile Driving;Biological;Biological Process;carcinogenesis;Cell Line;Chemotaxis;Chronic;Chronic Disease;Cirrhosis;Coculture Techniques;Communities;Compensation;Complex;cytokine;Data;Development;Diabetes Mellitus;Disease;Disease Progression;eicosanoid metabolism;Eicosanoid Production;Eicosanoids;Etiology;Event;experimental study;Extravasation;Fatty Liver;gain of function;Genes;Genetic;Glucose;Hepatic;Hepatitis;Hepatocyte;human disease;Hyperinsulinism;Immune;immune activation;improved;In Vitro;in vivo;in vivo Model;Inflammation;Inflammatory;insight;Insulin Resistance;insulin signaling;Insulin Signaling Pathway;Knock-out;Knowledge;Kupffer Cells;Link;lipid biosynthesis;lipid mediator;lipid metabolism;Lipids;Lipoxygenase;Liver;Liver diseases;loss of function;Macrophage;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Metabolic;metabolomics;Mitochondria;Modeling;Molecular;mouse model;multiple omics;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;oxidation;Oxidative Stress;Pathway interactions;Patient-Focused Outcomes;Patients;Phagocytosis;Phenotype;phosphoproteomics;PI3K/AKT;Population;preservation;Primary carcinoma of the liver cells;Production;programs;Prostaglandins;protein expression;Protein Isoforms;Proteomics;Proto-Oncogene Proteins c-akt;PTEN gene;Regulation;Role;Signal Transduction;Terminal Disease;Testing;Therapeutic;Toll-like receptors;transcriptomic profiling;Vascularization;Work

PROJECT_TITLE: Hepatic Steatosis Induced by Bioactive Lipids

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-7 (O1)]


PHR: These studies will define the role of metabolite lactate in regulating increased proliferation and survival of pulmonary vascular cells in pulmonary arterial hypertension (PAH); will provide insights into the molecular mechanisms of lactate regulation and function that are important in pathogenesis of PAH; and will explore whether lactate signaling could serve as a target pathway for pulmonary vascular remodeling-focused therapeutic interventions.

PI_NAMEs: GONCHAROVA, ELENA  (contact)

PROGRAM_OFFICER_NAME: SUTLIFF, ROY L

PROJECT_TERMS: Apoptosis;Area;Attenuated;Automobile Driving;cancer cell;cancer therapy;Cell Proliferation;Cell secretion;Cell Survival;Cells;Cessation of life;Clinical Trials;Data;Development;Disease;Disease Progression;Distal;DNA Topoisomerases;EMILIN1 gene;Endothelial Cells;FDA approved;Fibroblasts;FRAP1 gene;Glycolysis;HIF1A gene;Histones;Human;Hypoxia;In Vitro;in vivo;Induction of Apoptosis;inhibitor;insight;Knockout Mice;lactate dehydrogenase A;Link;Lung;Lysine;Metabolic;Metabolism;Molecular;Molecular Target;Mus;novel;Outcome;overexpression;Pathogenesis;Pathway interactions;Phenotype;Platelet-Derived Growth Factor;Play;Post-Translational Protein Processing;Production;Proliferating;Publishing;pulmonary arterial hypertension;pulmonary arterial pressure;Pulmonary arterial remodeling;pulmonary artery endothelial cell;Pulmonary artery structure;Pulmonary Hypertension;pulmonary vascular cells;pulmonary vascular remodeling;Rattus;Regulation;Reporting;Resistance;right ventricular failure;Role;Signal Transduction;Signaling Molecule;Smooth Muscle Myocytes;Structure of parenchyma of lung;Testing;Therapeutic Intervention;Tissue Sample;Topoisomerase;Transforming Growth Factor beta;tumor microenvironment;tumor progression;Up-Regulation

PROJECT_TITLE: LDHA-lactate signaling in pulmonary arterial hypertension

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 RCCS-E (03)]