NIH_SPENDING_CATS: Genetics

ORG_DEPT: BIOLOGY

PHR: Project Narrative The centromere is the DNA locus linking chromosomes to the mitotic spindle machinery. Defects in centromere function can lead to chromosome breakage, mis-segregation and aneuploidy, features of many cancer cells. While the field has made major strides in understanding the protein machine (kinetochore) that links the centromere to microtubules, we are just beginning to make inroads into understanding the biophysical properties of the centromere.

PI_NAMEs: BLOOM, KERRY S (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Address;Anaphase;Aneuploidy;Appearance;arm;Behavior;Binding Sites;Biochemical;Biochemical Process;bioimaging;Biophysical Process;biophysical properties;cancer cell;Cell division;Cell Nucleolus;Cells;Centromere;Characteristics;Chromatin;Chromatin Loop;Chromosome Breakage;Chromosome Segregation;Chromosome Structures;Chromosomes;cohesin;cohesion;Collaborations;Complex;computerized tools;condensin;Defect;density;DNA;DNA Sequence;Engineering;Ensure;Equus caballus;experience;Fission Yeast;Flowers;fluorescence imaging;Fluorescent Probes;fly;forest;Foundations;Goals;homologous recombination;Human;in silico;innovation;insight;Kinetochores;Laboratories;Length;Link;Mathematics;Mechanics;Mediating;Metabolism;Metaphase;microscopic imaging;Microtubules;Mitosis;Mitotic spindle;Modeling;monomer;Moths;Nonhomologous DNA End Joining;Nuclear;Nucleoplasm;Pathway interactions;Peptides;Phase;Phylogeny;Physics;Plants;Plus End of the Microtubule;Polymers;Property;Protein Complex Subunit;Proteins;Radial;repaired;segregation;self assembly;self organization;Series;Signal Transduction;simulation;Sister;Sister Chromatid;Site;small molecule;Solvents;Structure;System;Temperature;Testing;theories;Time;Yeasts

PROJECT_TITLE: Structure and Function of a Eukaryotic Centromere

STUDY_SECTION: NCSD

STUDY_SECTION_NAME: Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section[NCSD]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Clinical Research;Neurosciences

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Ongoing dynamics in brain spontaneous activities carry a wealth of information that informs brain function in health and disease. Despite intensive study, mechanisms causing such intrinsic brain dynamics remain incompletely understood. In this proposal, we will integrate complementary, multi- faceted neuroimaging techniques to pioneer a novel framework that allows us to precisely link large- scale brain functional circuits with a broad range of metabolic and neurochemical processes, establishing an important step toward illuminating the fundamental mechanisms driving large-scale brain dynamics.

PI_NAMEs: CHEN, JINGYUAN  (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Address;Alzheimer's Disease;Arousal;Automobile Driving;Behavior;Binding;Biophysics;blood oxygen level dependent;Blood Vessels;Brain;Brain Mapping;Brain region;career;Clinical;clinical biomarkers;clinical translation;Cognition;Cognitive;cognitive task;Complex;cost;Coupled;Disease;Dissociation;Dopamine;Electroencephalography;Exhibits;fluorodeoxyglucose;Foundations;Functional Magnetic Resonance Imaging;functional magnetic resonance imaging/electroencephalography;Glucose;glucose metabolism;Goals;Grant;Health;hemodynamics;Human;Induced Neurons;innovation;interest;Length;Link;Magnetic Resonance Imaging;Maps;Measures;Mental Depression;Mental disorders;Mentors;Metabolic;Methodology;Modality;multimodality;Nature;neural;neurochemistry;Neurodegenerative Disorders;neuroimaging;Neuromodulator;neuron component;Neurons;neurophysiology;neuroregulation;Neurosciences;Norepinephrine;novel;Outcome;Pathologic;Pattern;Physiology;Population;Positron-Emission Tomography;Process;programs;Protocols documentation;Regulation;Research;Research Personnel;Resolution;Rest;Sampling;Scanning;Schizophrenia;Sensitivity and Specificity;Series;signal processing;Signal Transduction;skills;Specificity;statistics;stem;Stimulus;Structure;Syndrome;Techniques;Time;tool;Training;Translational Research;Variant;vascular factor;Visual

PROJECT_TITLE: Probing the Biophysical Basis of Large-Scale Brain Dynamics Using Simultaneous PET/fMRI and EEG/PET/fMRI

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Infectious Diseases;Inflammatory Bowel Disease;Microbiome;Nutrition;Prevention

ORG_CITY: DAVIS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: PUBLIC HEALTH RELEVANCE STATEMENT Ulcerative colitis is associated with an imbalance in host-associated microbial communities (dysbiosis), but the mechanisms involved in disrupting homeostasis and the consequences of a microbial imbalance for human health remain poorly defined. Here we will study the mechanisms through which colitis drives an expansion of potentially harmful bacteria in the colon and how this bacterial bloom escalates colitis. The resulting knowledge will usher in important conceptual advances on how the host maintains homeostasis in the gut, which will have a strong potential to exert a high impact on research in this field.

PI_NAMEs: BAUMLER, ANDREAS J (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: absorption;Anaerobic Bacteria;Animal Model;Anti-Inflammatory Agents;Antibiotic Therapy;Automobile Driving;Bacteria;Bioenergetics;Childhood;Colitis;Colon;colon microbiota;Complex;Data;Disease;dysbiosis;Ecology;Ecosystem;Enterobacteriaceae;Environment;Environmental Risk Factor;Epithelial Cells;Epithelium;expectation;experimental study;Exposure to;Family member;Fermentation;Fiber;Foundations;Funding;genetic risk factor;Goals;Growth;gut homeostasis;gut inflammation;gut microbiota;Health;Homeostasis;host-associated microbial communities;Human;Hydrogen Peroxide;Hypoxia;Inflammation;innovation;Journals;knowledge of results;Mediating;Metabolism;microbial;microbial community;microbiota;Mitochondria;mucosal microbiota;Mucous body substance;Mucous Membrane;Mus;nutrition;Outcome;Oxidative Phosphorylation;Oxygen Consumption;Pathogenesis;Pharmaceutical Preparations;Productivity;public health relevance;Publications;Research;Salicylic Acids;Secondary to;Solid;sound;Surface;Testing;tool;Ulcerative Colitis;Work

PROJECT_TITLE: Exacerbation of Colitis by Enterobacteriaceae

STUDY_SECTION: GMPB

STUDY_SECTION_NAME: Gastrointestinal Mucosal Pathobiology Study Section[GMPB]


NIH_SPENDING_CATS: Cancer;Emerging Infectious Diseases;Genetics;Hematology;Infectious Diseases;Lymphatic Research;Lymphoma;Rare Diseases

ORG_CITY: BALTIMORE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: AIDS malignancy-associated human herpesvirus 8 (HHV-8) encodes four interferon regulatory factor homologues (vIRFs); we have found that one of these, vIRF-3, suppresses expression of viral proteins RTA, required for entry of the virus into the lytic (productive) phase, and viral interleukin-6 (vIL-6), which promotes lytic replication and is implicated in HHV-8 malignant pathogenesis. The research outlined in this application will determine the mechanisms involved in these newly-identified activities of vIRF-3 and will involve analysis of a vIRF-3-derived peptide sequence that we have found is able to enhance vIRF-3 expression, thereby providing a means to artificially control expression of this lytic suppressor. The proposed study will characterize previously unknown functions of vIRF-3, vIRF-3 regulation by a novel peptide reagent as a means of lytic suppression, and potentially provide the basis for development of antiviral and therapeutic strategies, via vIRF-3 manipulation and corresponding regulation of RTA, vIL-6, and productive replication.

PI_NAMEs: NICHOLAS, JOHN  (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;adaptive immune response;AIDS related cancer;Anti-viral Agents;antiviral drug development;Binding;Biological;Biological Assay;Biology;Cell Proliferation;Cell Survival;cell type;Cells;co-infection;Complex;Custom;Cycloheximide;cytokine;Dactinomycin;Data;density;Development;DNA Polymerase II;Elements;Endothelial Cells;Enhancers;EP300 gene;Epithelial Cells;Equilibrium;Etiology;expectation;Future;gammaherpesvirus;Gene Expression Regulation;Genes;Genetic Transcription;Growth;Growth Factor;HIV;HIV Infections;HIV/AIDS;Homologous Gene;Human Herpesvirus 8;Immune;Immune signaling;Infection;Interferon Regulatory Factor 2;Interferons;Interleukin-6;Investigation;Kaposi Sarcoma;Knock-out;Lentivirus;Lymphoma cell;Lytic;lytic gene expression;Lytic Phase;lytic replication;Macaca;Malignant - descriptor;Mediating;Mediator;Messenger RNA;Modeling;Molecular;Multicentric Angiofollicular Lymphoid Hyperplasia;novel;novel strategies;Oncogenic;pathogen;Pathogenesis;Peptides;Phase;Phenotype;Post-Transcriptional Regulation;posttranscriptional;primary effusion lymphoma;Process;Production;Productivity;promoter;protein aminoacid sequence;Proteins;Proto-Oncogenes;Publishing;Reagent;Regulation;Reporter;Reporting;Repression;Research;Ribosomes;RNA;Role;Signal Transduction;small molecule;Stress;System;Therapeutic;Therapeutic Agents;TP53 gene;Transcription Coactivator;Tumor Suppressor Proteins;Viral;viral fitness;Viral Genes;viral interferon regulatory factor;viral interferon regulatory factor-1;viral interferon regulatory factor-3;Viral Pathogenesis;Viral Physiology;Viral Proteins;Virus;Virus Diseases;virus host interaction;Virus Latency;Xeroderma Pigmentosum

PROJECT_TITLE: AIDS malignancy-associated human herpesvirus 8 viral interferon factor regulation of lytic-trigger and pathogenesis-associated viral RTA and vIL-6 proteins

STUDY_SECTION: HCAC

STUDY_SECTION_NAME: HIV Coinfections and HIV Associated Cancers Study Section[HCAC]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF NURSING

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Dissemination and Implementation Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Physical Injury - Accidents and Adverse Effects;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Trans women of color are at elevated risk of HIV, yet interventions to address upstream structural determinants of HIV in this population, including stigma-driven economic vulnerability and violence, are limited. The proposed work will evaluate how an innovative, gender-affirming cash transfer and economic empowerment intervention with trans women of color in Detroit can reduce violence and promote HIV prevention and care. Findings from this study and from a community needs assessment will be used to design a new intervention addressing structural determinants of health in collaboration with a community-based participatory research partnership.

PI_NAMEs: PEITZMEIER, SARAH  (contact)

PROGRAM_OFFICER_NAME: SENN, THERESA ELAINE

PROJECT_TERMS: Academy;Address;Affect;AIDS prevention;Applications Grants;Automobile Driving;Behavior;behavior change;Behavior Therapy;Biosocial;Black race;care outcomes;career;Caring;Collaborations;Communities;community based participatory research;community engaged intervention;community partners;community partnership;Data;design;Diagnosis;Economics;efficacy/implementation trial;empowerment;Epidemic;Equity;Ethnography;Evaluation;experience;Explosion;Focus Groups;food insecurity;Funding;Future;gender affirmation;gender-based violence;Health;HIV;HIV disparities;Homelessness;Housing;Hybrids;implementation science;Imprisonment;improved;Individual;Inequity;informant;innovation;Intervention;Intervention Studies;Intervention Trial;Interview;intimate partner violence;Investments;Israel;Knowledge;Latina;Learning;Maps;Mental Health;Mental health promotion;Mentors;Mentorship;Michigan;National Institute of Mental Health;Nature;Needs Assessment;Observational Study;Personal Satisfaction;pilot trial;Population;Poverty;prevent;Process;professor;programs;Protocols documentation;Public Health Schools;racial disparity;racism;Reporting;Research;Research Personnel;Resource Sharing;Resources;Risk;scale up;School Nursing;Science;Scientist;service providers;sex;Sexism;skills;social stigma;structural determinants;structural health determinants;Structure;syndemic;theories;therapy design;Time;Training;Training Activity;Training Support;transgender;transgender women;trauma symptom;trial design;United States National Institutes of Health;Universities;Violence;violence prevention;Woman;women of color;Work;Writing

PROJECT_TITLE: Community-Engaged Structural Approaches to Prevent Violence and Improve HIV Prevention and Care Outcomes Among Trans Women of Color

STUDY_SECTION: HIBI

STUDY_SECTION_NAME: HIV/AIDS Intra- and Inter-personal Determinants and Behavioral Interventions Study Section[HIBI]


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Dental, Oral, and Craniofacial Disease;Neurosciences;Nutrition

ORG_CITY: NORMAN

ORG_NAME: UNIVERSITY OF OKLAHOMA

ORG_STATE: OK

PHR: The proposed research aims to define genetic and neural circuit features of taste neurons that pertain to their role in multimodal brain pathways associated with affect. These concepts are important for understanding hedonic function in taste neurons and their influence on ingestive preference behaviors that impact nutritional status and human health. Studies will also bear on how taste sensations may intersect with and modulate pain- related signaling.

PI_NAMEs: LEMON, CHRISTIAN H (contact)

PROGRAM_OFFICER_NAME: SABRI, MERAV

PROJECT_TERMS: Affect;Affective;Alcohol dependence;Amygdaloid structure;Anesthesia procedures;Animals;Anorexia Nervosa;Area;avoidance behavior;Award;Behavior;Behavioral;behavioral response;Brain;brain pathway;Brain Stem;Calcitonin Gene-Related Peptide;Cells;Code;Communication;Complex;Cycloheximide;Data;Disease;Dynorphins;Electrophysiology (science);Emotional;Emotions;Esthesia;feeding;Fiber;Food;Genes;Genetic;Goals;Health;hedonic;Human;in vivo;Ingestion;Lateral;Limb structure;Link;Liquid substance;Maps;Measurement;Measures;Mediating;Modality;multimodality;Mus;neural;neural circuit;Neurons;neurophysiology;neurotransmission;Nociception;Nociceptive Stimulus;novel;Nutritional status;Obesity;Optics;optogenetics;Oral;Oral cavity;Pain;parabrachial nucleus;Pathway interactions;Pattern;Physiological;pleasure;preference;Process;protective behavior;Quinine;Research;response;Rodent;Role;Sensory;Shapes;Signal Transduction;somatosensory;Spinal;Stimulus;Tail;Taste Perception;Taste preferences;taste stimuli;Temperature;Testing;Trigeminal System;Water

PROJECT_TITLE: Taste and Somatosensory Processing

STUDY_SECTION: NIC

STUDY_SECTION_NAME: Neuroscience of Interoception and Chemosensation Study Section[NIC]


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: TUCSON

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Noise trauma can lead to tinnitus and auditory processing disorders. PV neuron loss is implicated in those auditory pathologies. We propose to examine the roles of TNFR1 and TNFR2 in PV neuron loss as potential treatment targets.

PI_NAMEs: BAO, SHAOWEN  (contact)

PROGRAM_OFFICER_NAME: POREMBA, AMY

PROJECT_TERMS: Acceleration;Acute;Auditory;Auditory area;auditory pathway;Auditory Perceptual Disorders;auditory processing;Behavior;Brain;Brain Diseases;Cell Death;Cell Survival;Cells;Custom;cytokine;Cytoprotection;Data;design;Detection;Disease;Enterobacteria phage P1 Cre recombinase;Exposure to;Functional disorder;hippocampal pyramidal neuron;Image;Immune response;Inflammatory;Interneurons;knock-down;Link;Mediating;mouse model;Mus;Nervous System Disorder;Neurodegenerative Disorders;neuroinflammation;neuron loss;Neuronal Dysfunction;Neurons;Neurotransmitters;Noise;noise exposure;noise trauma;Optics;optogenetics;Output;Parvalbumins;patch clamp;Pathology;Phenotype;Phosphorylation;Physiologic pulse;Population;prevent;Probability;Publishing;receptor;Receptors, Tumor Necrosis Factor, Type II;Reporter;Research;response;RIPK3 gene;Rodent Model;Role;Signal Transduction;Slice;small hairpin RNA;Synapses;synaptic inhibition;Testing;Tinnitus;TNF gene;TNFRSF1A gene;TNFRSF1B gene;Transfection;Traumatic Brain Injury;Tumor Necrosis Factor Receptor;Viral;Viral Vector;Visualization

PROJECT_TITLE: TNF-α Signaling in Noise Trauma-Induced PV Neuron Loss and Dysfunction

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: CHICAGO

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE This project will develop a tumor-targeted and -activated nanomedicine with a significantly enhanced therapeutic index than the standard of care for metastatic colorectal (mCRC), which is currently associated with high rates of morbidity and mortality. This nanomedicine will further synergize with immune checkpoint blockade for effective chemo-immunotherapy of mCRC. The proposed project has the potential to provide a clinical candidate for effective therapy of mCRC and other metastatic cancers.

PI_NAMEs: LIN, WENBIN  (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: Address;Agonist;anti-cancer;anti-PD-L1;anti-PD-L1 antibodies;Antigen Presentation;Antigens;antitumor effect;Binding;Biodistribution;cancer cell;Cancer Etiology;Cancer Model;cancer therapy;Cell-Mediated Cytolysis;Cessation of life;chemotherapy;Cholesterol;Circulation;clinical candidate;clinical care;clinical translation;Clinical Trials;Collaborations;colon cancer patients;Colorectal Cancer;Colorectal Neoplasms;Combination Drug Therapy;Cyclic GMP;cytokine;Deposition;Development;Dinucleoside Phosphates;Disseminated Malignant Neoplasm;Distant;Distant Metastasis;docetaxel;Drug Delivery Systems;Drug Kinetics;effective therapy;Epithelial Cells;Exhibits;Gene Activation;Goals;Half-Life;Hybrids;hydrophilicity;Hydrophobicity;Immune;immune checkpoint blockade;Immuno-Chemotherapy;immunogenic;immunogenic cell death;Immunologic Memory;Immunologics;Immunotherapy;improved;In Vitro;in vivo;Interferon Type I;Ions;Lesion;Ligands;Low Density Lipoprotein Receptor;Low-Density Lipoproteins;Mediating;Metals;metastatic colorectal;Methods;Microsatellite Instability;Mismatch Repair;Mismatch Repair Deficiency;Modality;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;multidisciplinary;multimodality;Mus;nanomedicine;nanoparticle;nanoscale;nanotherapeutic;Neoplasm Metastasis;novel;novel therapeutics;overexpression;oxaliplatin;Paclitaxel;particle;Pathway interactions;Patients;Pattern;Periodicity;Permeability;Pharmaceutical Preparations;polymerization;Polymers;Pre-Clinical Model;Prodrugs;Prognosis;receptor mediated endocytosis;Regimen;Research;Resistance;response;side effect;Signal Transduction;Solid;standard of care;Stimulator of Interferon Genes;subcutaneous;Survival Rate;synergism;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;Therapeutic Index;tool;Toxic effect;transcriptome sequencing;tumor;Tumor Antigens;Tumor Immunity;tumor microenvironment;Tumor Tissue;uptake

PROJECT_TITLE: Tumor-Targeted Multimodality Nanoscale Coordination Polymers for Chemo-Immunotherapy of Metastatic Colorectal Cancer

STUDY_SECTION: NANO

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Biotechnology;Congenital Structural Anomalies;Genetics;Osteogenesis Imperfecta;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: We will use the gene-editing technique i-GONAD to insert gene-traps into 4 different mouse models of moderate and severe OI. This enables public repositories to distribute the mice and investigators to study tissue-specific effects of inducing endogenous levels of mutant type 1 collagen expression after Cre- recombination. We will study the effect of inducing mutant type 1 collagen expression in hypertrophic chondrocytes and their descendants.

PI_NAMEs: WARMAN, MATTHEW L (contact)

PROGRAM_OFFICER_NAME: CHEN, FAYE H

PROJECT_TERMS: Adult;Affect;Alleles;Animals;Body System;bone;Bone Density;bone mass;Breeding;Cardiac;Cell Therapy;cell type;Cells;Chest;Chondrocytes;Clinical;COL1A1 gene;COL1A2 gene;Collagen;Collagen Gene;Collagen Type I;Compensation;Cre driver;Data;Disease;Dominant-Negative Mutation;Enterobacteria phage P1 Cre recombinase;Epiphysial cartilage;Evaluation;experience;Foundations;Funding;gene editing technology;Gene Modified;gene-editing approach;Genes;Genetic;Genetic Recombination;Goals;Growth;Heart;Human;Individual;inducible Cre;insight;interest;Introns;Knowledge;Laboratories;Ligaments;Lung;Marrow;Mediating;Modeling;mouse model;Mouse Strains;Multiple Fractures;Mus;mutant;Mutation;Osteoblasts;Osteogenesis Imperfecta;osteoprogenitor cell;Patients;Pharmaceutical Preparations;Phenotype;prevent;Production;progenitor;Property;Proteins;public repository;Publishing;radiological imaging;repository;Research Personnel;Resources;Reverse Transcriptase Polymerase Chain Reaction;rib bone structure;Scientist;Severities;skeletal;Skin;Source;System;Technology;Tendon structure;The Jackson Laboratory;Tissue-Specific Gene Expression;Tissues;TNFSF5 gene;transdifferentiation;United States National Institutes of Health;Vertebral column

PROJECT_TITLE: Conditional mouse models with dominant negative Osteogenesis Imperfecta

STUDY_SECTION: SBDD

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


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biomedical Imaging;Complementary and Integrative Health;Emerging Infectious Diseases;Infectious Diseases;Natural Products;Wound Healing and Care

ORG_CITY: EAST LANSING

ORG_NAME: MICHIGAN STATE UNIVERSITY

PHR: Project Narrative Pathogenic bacteria form biofilms, which are layers of bacteria within a matrix, and inside these structures the bacteria are resistant to many different antibiotics. Pseudomonas aeruginosa, a major pathogen that forms biofilms in the infections it causes, is resistant to many antibiotics because of this biofilm formation. We have identified compounds and plant-derived substances that augment antibiotic activity against P. aeruginosa biofilms, and propose to test these substances in a novel biofilm wound infection model in animals to create new treatments.

PI_NAMEs: HARDY, JONATHAN W (contact);WATERS, CHRISTOPHER M

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Animal Model;Animals;Antibiotic Resistance;Antibiotics;antimicrobial;Bacteria;Bacterial Antibiotic Resistance;bacterial metabolism;bacterial resistance;Berberine;Biological;Biological Assay;bioluminescence imaging;Cessation of life;Chronic;Ciprofloxacin;combat;Combined Antibiotics;Complex;Creosote;design;Development;Dose;efficacy testing;Exclusion;experimental study;FDA approved;Goals;Goldenseal;high throughput screening;Hour;Hydrastis;In Vitro;in vivo;in vivo bioluminescence imaging;in vivo evaluation;Individual;Infection;innovation;Intervention;Larrea;Lung infections;Measures;Mediating;Microbial Biofilms;Modeling;mouse model;multidrug-resistant Pseudomonas aeruginosa;Mus;natural antimicrobial;Natural Products;non-invasive imaging;novel;pathogen;pathogenic bacteria;Persons;Pharmaceutical Preparations;Phytochemical;Plant Extracts;Plants;Process;Property;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Regimen;Reporting;Research;Resistance;resistance mechanism;screening;small molecule libraries;Source;Speed;Structure;synergism;System;Testing;Therapeutic;Time;Tobramycin;Treatment Protocols;Triclosan;Water;wound;wound biofilm;Wound Infection;Wound models

PROJECT_TITLE: Novel Antibiofilm Treatments for Pseudomonas aeruginosa Infection

STUDY_SECTION: DDR

STUDY_SECTION_NAME: Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section[DDR]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Hearing Loss;Neurosciences;Pediatric;Rehabilitation

ORG_CITY: Aurora

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Infants who are hard-of-hearing (IHH) are at risk for poor auditory development and speech perception even when diagnosed and fit with hearing aids by 3 months of age. Efforts outlined will advance our understanding of speech perception and auditory skill development among IHH compared to a cohort of age-matched peers with typical hearing. This project is relevant to NIDCD's mission to identify if changes to early intervention are needed to improve communication outcomes including future employability, as well as reducing the societal costs of childhood hearing loss.

PI_NAMEs: UHLER, KRISTIN MICHELLE (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Address;Affect;Age;Age Months;Auditory;Behavioral;Brain;Child;childhood hearing loss;Clinical;Cochlear implant procedure;cohort;Communication;Cueing for speech;Cues;Data;Detection;Development;Developmental Process;Diagnosis;Discrimination;Early Intervention;Electroencephalography;experience;Exposure to;Felis catus;Foundations;Future;Goals;hard of hearing;Hearing;Hearing Aids;hearing impairment;improved;Infant;Intervention;Language;Language Development;language outcome;Life;Maps;Measures;Mission;Modeling;National Institute on Deafness and Other Communication Disorders;Noise;non-Native;normal hearing;Outcome;Pathway interactions;peer;permanent hearing loss;personalized intervention;Physiological;Predisposition;response;Review Literature;Risk;Scalp structure;Seminal;Sensory;Shapes;skill acquisition;skills;societal costs;sound;Speech;Speech Development;Speech Discrimination;Speech Perception;Speech Sound;tool;Work

PROJECT_TITLE: The impact of auditory access on the development of speech perception


ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

ORG_STATE: FL

PHR: Project Narrative Bladder cancer has long been recognized as a malignancy that is responsive to immune-based therapy, however the median overall survival is slightly over one year in patients with metastatic disease. Therefore, novel, more precise treatment strategies are clearly needed. Here, we will use mathematical modeling and optimization to design robust treatment protocols for adoptive T cell therapies.

PI_NAMEs: PILON-THOMAS, SHARI ;REJNIAK, KATARZYNA ANNA (contact)

PROGRAM_OFFICER_NAME: CARDONE, MARCO

PROJECT_TERMS: Adoptive Cell Transfers;Adoptive Immunotherapy;Antigen-Presenting Cells;Autologous;Bladder;Bladder Neoplasm;Calibration;cancer cell;Cancer Etiology;Cancer Histology;cancer infiltrating T cells;Cancer Patient;cancer therapy;cancer type;Catheters;CD8B1 gene;Cell Communication;Cell model;Cessation of life;Characteristics;chemotherapy;Clinical;Clinical Trials;clinically relevant;Combined Modality Therapy;Computer software;Data;Dendritic Cells;design;Disease;Dose;Effectiveness;Excision;Future;Generations;Histology;Human Characteristics;Immune checkpoint inhibitor;Immunologist;Immunotherapy;improved;in silico;In Vitro;in vivo;Infiltration;Infusion procedures;Intervention;intravesical;Intravesical Administration;Malignant neoplasm of urinary bladder;Malignant Neoplasms;mathematical model;Mathematics;men;Metabolic;Methodology;Methods;Microscopic;Modeling;Morphology;mortality;mouse model;neoplastic cell;novel;Organ;patient derived xenograft model;Patients;peripheral blood;Pharmaceutical Preparations;Phase;pre-clinical;Pre-Clinical Model;predictive modeling;Procedures;Property;Protocols documentation;Research;Resected;response;Schedule;Signal Transduction;simulation;Stress;success;T cell infiltration;T cell therapy;T-Lymphocyte;Therapeutic;Toxic effect;treatment optimization;Treatment Protocols;treatment strategy;tumor;tumor microenvironment;Vaccine Therapy;Vaccines;virtual;Woman;Work

PROJECT_TITLE: Mathematical Model-Guided Adoptive Immunotherapy in Bladder Cancer

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Clinical Research;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Prevention;Recovery Support Services;Rural Health;Screening and Brief Intervention for Substance Misuse;Social Determinants of Health;Substance Misuse

ORG_CITY: RESEARCH TRIANGLE PARK

ORG_NAME: RESEARCH TRIANGLE INSTITUTE

ORG_STATE: NC

PHR: PROJECT NARRATIVE Heavy drinking is a leading cause of preventable death, and untreated alcohol use disorder (AUD) has economic and social costs that are due in part to disparities in access to alcohol health services. This study will use existing survey and administrative data to simulate multiple, simultaneous improvements in access to care across the continuum from screening for unhealthy drinking to treatment and recovery support to model long- term impacts on recovery from AUD. We expect study results to help inform efforts of clinicians, treatment providers, and policymakers to improve access to care to maximize the benefits within local cost constraints.

PI_NAMEs: KARRIKER-JAFFE, KATHERINE J. (contact)

PROGRAM_OFFICER_NAME: WHITAKER, DAMIYA EVE

PROJECT_TERMS: access disparities;Accident and Emergency department;Address;alcohol availability;Alcohol consumption;alcohol related problem;alcohol use disorder;Alcoholics Anonymous;Alcohols;barrier to care;Calibration;California;Caring;Clinic;college;Communities;Complex;Continuity of Patient Care;cost;cost effective;cost effective intervention;cost effectiveness;cost estimate;Costs and Benefits;County;Data;Development;Dimensions;Disparity;disparity reduction;Distal;drinking;Economics;Ethnic Origin;Evaluation;Evidence based practice;Federally Qualified Health Center;Funding;Future;Gender;Geographic Locations;Geography;Goals;health care availability;health care service utilization;health care settings;health disparity;Health Personnel;Health Services;Health Services Accessibility;Heavy Drinking;HIV;Improve Access;improved;Individual;insight;Intervention;intervention effect;Investigation;Language;Literature;long term recovery;Medicaid;medical specialties;medication-assisted treatment;Mental Health;Methods;Minority Groups;Modeling;models and simulation;National Institute on Alcohol Abuse and Alcoholism;opioid epidemic;Outcome;outcome disparities;Pattern;Persons;Pharmaceutical Preparations;Policies;Policy Maker;Population;Prenatal care;preventable death;Primary Care;programs;Publishing;Race;Recovery;Recovery Support;reduced alcohol use;Research;Resources;Role;Rural;scale up;screening;screening and brief intervention;screening, brief intervention, referral, and treatment;service intervention;Services;Severities;simulation;Slide;sobriety;social;Socioeconomic Status;socioeconomics;Spanish;Specific qualifier value;Spottings;Statistical Computing;Statistical Models;Subgroup;Surveys;System;Testing;Texas;theories;Time;treatment disparity;treatment program;trend;underserved area;United States;Urbanicity;Violence;Vulnerable Populations;Woman

PROJECT_TITLE: Alcohol Use Disorder Treatment Simulation: Modeling treatment impacts on alcohol-related disparities


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

ORG_CITY: RONDEBOSCH

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: UNIVERSITY OF CAPE TOWN

PHR: Project Narrative In this project, we will develop a consolidated bioethics training program at the University of Cape Town Faculty of Health Sciences (UCT FHS), with as the flagship project the establishment of a two-year bioethics MSc degree. The UCT FHS is one of the biggest foreign recipients of NIH funding, and it is very important that we ensure high-quality research ethics training for all those working on NIH-funded projects. We will teach bioethics from perspectives of the African humanities, and will focus on the ethics of new and emerging health technologies.

PI_NAMEs: DE VRIES, JANTINA  (contact)

PROGRAM_OFFICER_NAME: SINA, BARBARA J

PROJECT_TERMS: Accreditation;Africa;African;Area;Award;Bioethics;Businesses;Child;Continuing Education;Course Content;Data;design;Development;Discipline;Educational Curriculum;Educational process of instructing;Ensure;Environment;Ethics;Evaluation;Event;experience;Faculty;Fees;frontier;Funding;Future;gateway course;Genomics;global health;Graduate Degree;graduate student;Health;health science research;Health Sciences;Health Technology;Humanities;improved;Income;Individual;International;Knowledge;Marketing;Measures;Medical Research;Mentorship;Monitor;Neurosciences;newspaper article;Ontology;open data;Outcome;Persons;podcast;Political Factor;Program Sustainability;programs;Research;Research Ethics;Resources;responsible research conduct;Scholarship;Schools;Shapes;social factors;Special Event;Stream;Students;Teacher Professional Development;Thinking;Time;Training;Training Programs;United States National Institutes of Health;Universities;Vision;Work

PROJECT_TITLE: Establishing an MSc in Global Health Ethics at the University of Cape Town

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-L(56)R]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Immunotherapy;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PHR: PROJECT NARRATIVE Lung epithelial cells (LECs) and stem cells are capable of antigen presentation and interaction with CD4 T cells; however, whether concomitant and future LEC functions are remodeled by the retrograde signaling that accompanies antigen presentation is unknown. The proposed studies will identify if engagement in an immune synapse remodels LEC functions during pneumonia (K99) and will test if CD4 T cells generate trained immunity in LECs post resolution of infection (R00). Thus, the proposed experiments will identify if LECs can be reprogrammed by CD4 T cells to preempt-, fight-, and recover from- pneumonia, and have the potential to establish LECs as immunomodulatory targets that can be trained to fight infections and cancers, promptly repair lungs, and maintain homeostasis.

PI_NAMEs: SHENOY, ANUKUL T (contact)

PROGRAM_OFFICER_NAME: ESPINOZA-PINTUCCI, MARISOL

PROJECT_TERMS: Address;Adoptive Transfer;Advisory Committees;Aging;Antigen Presentation;antigen test;Antigen-Presenting Cells;antimicrobial;Asthma;Boston;Cancer Biology;career;career development;CD4 Positive T Lymphocytes;Cell Communication;Cell Physiology;cell regeneration;Cell Reprogramming;Cell Separation;Cells;Cellular biology;Clinical;Committee Members;Communication;Communities;Computational Biology;cytokine;Data;Data Set;Disease;empowerment;Ensure;Epigenetic Process;epigenome;Epithelial Cell Proliferation;Epithelial Cells;Etiology;experience;experimental study;Faculty;fighting;Future;Genetic Transcription;Genetically Engineered Mouse;Goals;Grant;Health;High-Throughput Nucleotide Sequencing;Homeostasis;Human;Hypersensitivity;Immune;immune checkpoint blockade;Immunity;Immunologic Memory;immunological synapse;Immunology;immunoregulation;imprint;in vivo;Infection;Inhalation;Injury;injury and repair;innovation;Institution;Instruction;interest;Interferon Type II;Lung;lung regeneration;lung repair;Malignant Neoplasms;meetings;member;Memory;memory recall;Mentors;Microbe;microbial;Modeling;mouse model;Mucosal Immunity;Mucous Membrane;Mus;Myeloid Cells;Neutrophil Infiltration;novel;Patients;PD-1/PD-L1;Phenocopy;Pneumococcal Pneumonia;Pneumonia;Postdoctoral Fellow;preempt;programmed cell death ligand 1;programs;Recombinants;recruit;Recurrence;regenerative;repaired;Reporting;Research;research and development;resilience;Resolution;response;Role;Scientist;Signal Transduction;single cell ATAC-seq;single cell sequencing;single-cell RNA sequencing;skills;Sorting;stem cell biology;stem cell proliferation;stem cells;Streptococcus pneumoniae;T-Lymphocyte;Technology;tenure track;Testing;Tissues;tool;Training;transcription factor;transcriptomics;undergraduate student;Universities;Work

PROJECT_TITLE: Lung epithelial cell reprogramming by CD4 T cells

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Clinical Research;Mental Health;Mental Illness;Neurosciences;Prevention;Suicide;Suicide Prevention

ORG_CITY: NEW HAVEN

ORG_DEPT: PSYCHIATRY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Suicide among older adults is a significant public health concern, and social disconnection (SDC) has been identified as a key risk factor for suicide in this population. However, current understanding of neurobiological mechanisms implicated in SDC and suicide risk is limited, in part due to lack of mechanistic in vivo studies that are needed to identify modifiable targets for suicide prevention and intervention efforts. We propose to evaluate whether in vivo alterations in corticolimbic synaptic density may mediate the relation between SDC and longitudinal trajectories of late-life suicide risk, and whether this association differs in women vs. men.

PI_NAMEs: ESTERLIS, IRINA  (contact);PIETRZAK, ROBERT H

PROGRAM_OFFICER_NAME: LYONS, ELIZABETH ANNE

PROJECT_TERMS: Address;Adult;Adverse effects;Affect;Age;age group;aged;aging population;Amygdaloid structure;Animal Model;Animals;Anterior;Autopsy;Brain;Brain region;brain tissue;Cessation of life;clinically significant;cognitive function;cohort;Communities;Data;Decision Making;density;depressive symptoms;Development;Diagnostic;Emotional;environmental enrichment for laboratory animals;executive function;Family;Feeling suicidal;Fostering;Glycoproteins;Health;High Prevalence;Hippocampus;Human;ideation;Image;imaging study;in vivo;Individual;Intervention;Ketamine;late life;Left;Life;Link;Magnetic Resonance Imaging;male;Measures;Mediating;men;Modeling;Molecular;molecular imaging;molecular marker;multimodality;neurobiological mechanism;Neurocognitive;neuroimaging;neuromechanism;novel;older adult;older men;peer support;Pharmaceutical Preparations;Play;Population;Positron-Emission Tomography;pre-clinical;Prefrontal Cortex;Prevention strategy;Property;psychologic;psychosocial;Public Health;Public Policy;radioligand;recruit;Reporting;Risk;Risk Factors;Role;Sampling;Severities;sex;Sex Differences;social;social engagement;Social isolation;Social outcome;Socialization;suicidal;suicidal morbidity;suicidal risk;Suicide;Suicide prevention;suicide rate;Symptoms;Synapses;Synaptic Vesicles;synaptogenesis;Testing;therapy design;Woman;women versus men;Work

PROJECT_TITLE: Role of synaptic density in mediating the relation between social disconnection and late-life suicide risk


NIH_SPENDING_CATS: Cardiovascular;Climate-Related Exposures and Conditions;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Effects of Household Energy Combustion;Health Effects of Indoor Air Pollution;Immunization;Lung;Prevention;Social Determinants of Health;Vaccine Related;Women's Health Research

ORG_CITY: DHAKA

ORG_COUNTRY: BANGLADESH

ORG_FIPS: BG

ORG_NAME: INTERNATIONAL CTR/DIARRHOEAL DIS RES

PHR: PROJECT NARRATIVE The majority of the low- and middle-income countries (LMICs) including Bangladesh are confronted by severe environmental and occupational health related challenges because of rapid urbanization, unplanned industrialization and sub-optimal regulation, control, and remediation. The main research focus of this U01 proposal is to evaluate the changes in preclinical markers of cardio-respiratory and immune dysfunction in relation to reduction of household air pollution achieved through exclusive clean fuel use for cooking. We also plan to conduct pilot studies exploring health effects of industrial waste and garment industry work – two other emerging GEOHealth topics relevant for Bangladesh and many other LMICs. 1

PI_NAMEs: AHSAN, HABIBUL ;RAQIB, RUBHANA  (contact)

PROGRAM_OFFICER_NAME: JESSUP, CHRISTINE

PROJECT_TERMS: adaptive immunity;Adoption;Adult;Agriculture;Air Pollutants;Air Pollution;Anti-Inflammatory Agents;Antibodies;Antibody Response;Antigens;Area;Arrhythmia;Atherosclerosis;Award;Bangladesh;Behavioral;Biomass;biomass fuel;Blood Pressure;blood pressure elevation;Carbon Black;Cardiopulmonary;Cardiovascular Diseases;Cardiovascular system;carotid intima-media thickness;Cattle;Cellular Phone;chest computed tomography;Chicago;Child;Chronic;cohort;Communication;Communities;Companions;cooking;cost effective;cost efficient;COVID-19 vaccination;cytokine;Cytoplasmic Granules;cytotoxic;Data;deep learning;design;Developed Countries;Disease Outcome;Educational Intervention;Effector Cell;Electrocardiogram;endoplasmic reticulum stress;Ensure;Environmental Health;Exposure to;Fasting;follow-up;Functional disorder;Gases;global environment;Glycosylated hemoglobin A;Government;Grant;Granzyme;Health;Health Benefit;Health Hazards;Hour;Household;Household Air Pollution;Immune;immune function;Immune response;Immune System Diseases;Immunoglobulin G;Immunoglobulin M;Impairment;improved;Industrial Waste;Industrialization;Industry;Inflammation;Inflammatory;Inflammatory Response;Inflammatory Response Pathway;innovation;Interferon Type II;Intervention;Intervention Trial;Link;Lipids;Long-Term Effects;low and middle-income countries;Lung;Lymphocyte Subset;Measures;Memory;Metabolic dysfunction;Metabolic Marker;meter;mHealth;Mobile Health Application;Monitor;monocyte;mortality;Natural Immunity;Natural Killer Cells;non-smoking;novel;Occupational Health;Participant;Particulate Matter;perforin;Peripheral Blood Mononuclear Cell;Persons;Petroleum;Pilot Projects;Policies;Population;post intervention;pre-clinical;programs;Proteins;Public Health;pulmonary function;pulmonary function decline;Pulmonary Function Test/Forced Expiratory Volume 1;Pulmonary Pathology;Questionnaires;Randomized;Randomized, Controlled Trials;Regulation;remediation;Research;Resources;Risk;Social Impacts;South Asian;Surveys;T-Lymphocyte;T-Lymphocyte and Natural Killer Cell;Technology;Thoracic Radiography;TNF gene;Training;trend;ultrasound;Universities;Urbanization;Vaccines;Vital capacity;Woman;Women's Health;Wood material;Work;young woman

PROJECT_TITLE: 1/2-Bangladesh Center for Global Environmental and Occupational Health- Bangladesh

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-Q(70)R]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: MILWAUKEE

ORG_NAME: MARQUETTE UNIVERSITY

ORG_STATE: WI

PHR: We propose to adapt and expand methods for editing genes, initially developed in anole lizards, for use in other lizard species, particularly geckos. This project will facilitate comparisons of gene function across reptiles and other amniotes, including humans. Research derived from this project will improve knowledge of vertebrate developmental pathways, enable production of new lizard models relevant for understanding human disease, and deepen our understanding of the relationship between genotype and phenotype.

PI_NAMEs: GAMBLE, ANTHONY B (contact);MENKE, DOUGLAS BAY

PROGRAM_OFFICER_NAME: WETTERSTRAND, KRIS A

PROJECT_TERMS: Address;Biology;Clustered Regularly Interspaced Short Palindromic Repeats;Comparative Study;Development;Educational workshop;functional genomics;gene editing technology;gene function;gene-editing approach;Genes;Genetic;Genome;genome editing;genomic tools;Genotype;Human;human disease;improved;Knowledge;Lizards;Methods;Modeling;Modification;Oocytes;Pathway interactions;Phenotype;Production;Reptiles;Research;Research Personnel;Snakes;tool;Training;Work

PROJECT_TITLE: Collaborative Research: EDGE FGT: DEVELOPMENT OF FUNCTIONAL GENETIC TOOLS IN GECKOS


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

ORG_CITY: SEATTLE

ORG_NAME: ALLEN INSTITUTE

ORG_STATE: WA

PHR: PROJECT NARRATIVE (OVERALL) New tools for detailed molecular and spatial analysis of single cells are revolutionizing our understanding of the brain, but characterization of neuropathology in Alzheimer’s disease has been limited primarily to histology and tissue-level analyses. The current proposal aims to improve Alzheimer’s disease brain tissue banking and analysis, and adapt single cell transcriptomic, epigenomic and molecular spatial analysis methods developed under the BRAIN Initiative and the Allen Institute for Brain Science to Alzheimer’s disease in human postmortem tissues. These tools will be applied in an iterative and adaptive fashion to generate an increasingly refined foundational understanding of the molecular and structural progression of AD, identify transcriptional and spatial hallmarks of early AD pathology and affected molecular pathways, and create a catalytic open access dataset for the research community.

PI_NAMEs: CLOSE, JENNIE LEIGH;HAWRYLYCZ, MICHAEL ;HODGE, REBECCA DAWN;KEENE, CHRISTOPHER DIRK;LEIN, ED  (contact);MILLER, JEREMY A

PROGRAM_OFFICER_NAME: GRAY, ERIN EMILY

PROJECT_TERMS: Adult;Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease pathology;Alzheimer's disease related dementia;Anatomy;Architecture;Autopsy;Basic Science;Biological Assay;Brain;BRAIN initiative;Brain Mapping;brain research;brain tissue;Cell Nucleus;cell type;Cells;Cellular Neurobiology;Characteristics;Clinical;clinical phenotype;cohort;Collaborations;Collection;Communication;Communities;Complex;computerized data processing;Data;data access;Data Collection;data management;data modalities;data portal;data resource;Data Set;Deposition;design;Disease;Disease Resistance;disorder subtype;diverse data;Epigenetic Process;epigenome;epigenomics;Future;Generations;Genetic;Genetic Transcription;Genomic approach;Genomics;Goals;Health;Histology;Human;human tissue;improved;Infrastructure;insight;Leadership;Link;Maps;member;Methodology;Methods;Modernization;Molecular;Molecular Neurobiology;molecular pathology;Molecular Profiling;molecular scale;Neuroglia;Neurons;neuropathology;next generation;Organ;organizational structure;Pathogenesis;Pathologic;Pathology;Pathway interactions;Phase;Preparation;Progress Reports;Proteins;Research;Research Personnel;Resistance;Resolution;RNA;Science;Severities;single cell analysis;single cell genomics;Standardization;Strategic Planning;Techniques;Technology;Tissue Banks;tissue resource;Tissues;tool;transcriptome;transcriptomics;Universities;Visualization;Washington

PROJECT_TITLE: A platform for cell type-level transcriptomic, epigenomic and spatial interrogation of Alzheimer's disease


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Brain Disorders;Dementia;Genetics;Human Genome;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

PHR: PROJECT NARRATIVE (ADMIN CORE) The Administrative Core will provide the leadership and organizational structure to align the efforts of the individual Institutions, projects and researchers to meet the Center goals and milestones. This will involve integrating and aligning the efforts of the three Research Projects (neuropathology, transcriptomics and epigenomics, and spatial transcriptomics) and the Data Core. The Administrative Core will oversee the operational management including strategic planning, project management, progress reporting, fiscal management, manuscript and authorship planning, conflict resolution and support for collaboration and communication to create, integrate, and disseminate to the community a molecular and cellular understanding of Alzheimer’s disease.

PI_NAMEs: LEIN, ED  (contact)

PROJECT_TERMS: Achievement;Adherence;Adopted;Adoption;Advisory Committees;Alzheimer's Disease;Alzheimer's disease pathology;Architecture;Authorship;Brain;Budgets;cell type;Cells;Collaborations;Communication;Communities;Computer software;computerized data processing;conflict resolution;Data;Data Analyses;data exchange;data integration;data mining;data quality;data resource;data sharing;data standards;design;Ensure;Epigenetic Process;epigenomics;experience;Feedback;Fostering;Generations;Goals;hackathon;Health;Individual;Industry;Infrastructure;Institution;Joints;Leadership;Life Cycle Stages;Manuscripts;member;Molecular;Monitor;neuropathology;organizational structure;Pathogenesis;Performance;Phase;Procedures;Process;Production;programs;Progress Reports;Publications;Quality Control;Reporting;Research;Research Personnel;Research Project Grants;Resolution;Resources;Risk Management;Role;Science;Site;software development;Software Tools;Standardization;Strategic Planning;Structure;Supervision;synergism;Technology;Time;tool;transcriptomics;Universities;Visualization;Washington;web portal;working group

PROJECT_TITLE: Organization and architecture of a Center for cellular resolution analysis of Alzheimer's disease


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Data Science;Dementia;Genetics;Human Genome;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

PHR: PROJECT NARRATIVE (DATA CORE) The AD Center will create and manage large-scale datasets of different experimental modalities, originating from member institutions using centralized data infrastructure to facilitate data storage, processing and analysis via a community-accessible data portal. There is an increasing need to enhance data interoperability and harmonization among researchers to allow meaningful data analysis and simplified data accessibility for reuse; hence, one of the objectives of the AD Data Core will be to enable cross-modality search, analysis and visualization of cell type-specific information from related datasets. We will build new infrastructure to support the novel tissue and experimental workflows being generated by AD Center projects, and customize software management systems to manage and store data and metadata, to produce an integrated data service platform for maximum research community impact.

PI_NAMEs: HAWRYLYCZ, MICHAEL  (contact)

PROJECT_TERMS: Acceleration;Address;Aging;Alzheimer's Disease;Alzheimer's disease pathology;analysis pipeline;Anatomy;arm;Atlases;Biological;Brain;brain cell;BRAIN initiative;cell type;Cells;Censuses;Clinical;Clinical Data;Cognition Disorders;cohort;Communities;Community Developments;Complex;Computer software;computerized data processing;Custom;Data;data access;data acquisition;Data Analyses;data centers;Data Display;data exchange;data framework;data harmonization;data infrastructure;data ingestion;data integration;data interoperability;data management;Data Management Resources;data modalities;data portal;Data Reporting;data repository;data resource;Data Set;data sharing;data standards;Data Storage and Retrieval;data tools;data visualization;Databases;Dementia;design;Dimensions;Epigenetic Process;epigenomics;Equipment and supply inventories;feature extraction;Feedback;Foundations;Funding;Future;Gene Expression;General Population;Generations;Goals;Growth;hackathon;Histologic;Human;Image;In Vitro;in vivo;Information Dissemination;Infrastructure;Institution;Internet;Knowledge;Laboratories;large scale data;Machine Learning;Management Information Systems;Maps;member;Metadata;Methodology;Methods;Modality;Molecular;Molecular Profiling;multimodality;Mus;Nature;Neurobiology;Neurons;neuropathology;Neurosciences;nonhuman primate;novel;Ontology;Output;outreach;Pathologic;Patients;Preparation;Process;Reference Standards;Research;Research Design;Research Personnel;Research Project Grants;research study;Resources;scaffold;Science;Scientist;Semantics;Services;single cell analysis;Structure;Surveys;synergism;System;systems research;Taxonomy;Techniques;Tissues;tool;tool development;Training;transcriptomics;Traumatic Brain Injury;United States National Institutes of Health;unsupervised learning;usability;Visualization;web portal;web-based tool;webinar

PROJECT_TITLE: A data resource for high resolutionneuropathological and omics analysisof Alzheimer's disease


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Congenital Structural Anomalies;Diabetes;Kidney Disease;Pediatric;Polycystic Kidney Disease

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

PHR: PROJECT NARRATIVE The proposed research will benefit both clinical and basic science fields by investigating the contributions of HCO3- buffering in type 2 diabetes and polycystic kidney disease. The proposed research is impactful because it probes a metabolic pathway implicated in type 2 diabetes and a proliferative pathway associated with polycystic kidney disease.

PI_NAMEs: BROWN, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: absorption;Acid-Base Equilibrium;Adenylate Cyclase;Adult;Apical;Basic Science;Beta Cell;Bicarbonates;Buffers;Cell Physiology;Cells;Cellular Metabolic Process;Chemosensitization;Clinical Sciences;Code;combat;Compensation;Complement 3d Receptors;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Cyst;Depressed mood;Development;Diabetes Mellitus;diabetic;Distal;Duct (organ) structure;Environment;Etiology;Event;Excretory function;Failure;Functional disorder;Genes;Glucose;glucose tolerance;Glycolysis;Goals;Human;Hyperglycemia;Impairment;improved;In Vitro;in vivo;in vivo Model;Inflammation;Insulin;insulin secretion;Intercalated Cell;islet;Kidney;Kidney Diseases;Lead;Maintenance;Mediating;Mediator;MEKs;Metabolic;Metabolic acidosis;Metabolic Pathway;Metabolism;Mitochondria;Modeling;Mus;Nephrology;Nephrons;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;Output;Pancreas;Pathway interactions;pH Homeostasis;Phase;Play;Polycystic Kidney Diseases;Positioning Attribute;Postdoctoral Fellow;preservation;Prevalence;prevent;programs;Proliferating;Protein Isoforms;Regulation;Repression;Research;Role;sensor;Signal Pathway;Signal Transduction;solute;Structure of beta Cell of islet;symporter;Testing;therapeutic evaluation;transcriptomics;treatment strategy;Work

PROJECT_TITLE: NBCe1-mediated Regulation of HCO3- is a Novel Mechanism Underlying Metabolic Reprogramming and Cystogenesis


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

PHR: PROJECT NARRATIVE (PROJECT 1) Detailed analysis of cellular, molecular, and genetic information as well as spatial resolution of affected cell types is a key goal in understanding the cellular processes that give rise to Alzheimer’s disease. The current standard neuropathology protocols for sampling tissue, generally formalin-fixed paraffin-embedded tissue preservation, do not lend themselves to in-depth chemical and molecular analysis, nor does traditional neuropathological characterization of disease states provide sufficient detail to determine the pathophysiology of altered genes and proteins. When successfully completed, this project will have combined traditional and quantitative neuropathologic methods to better characterize AD pathologic stages and identify cases for Projects 2 and 3 and transformed donated brain tissue sampling and preservation in order to promote modern techniques and preserve valuable human tissue in a manner that is amenable to state-of-the-art molecular profiling and cell type analysis.

PI_NAMEs: KEENE, CHRISTOPHER DIRK (contact)

PROJECT_TERMS: Abbreviations;Adult;Affect;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease related dementia;Amyloid beta-Protein;Astrocytes;Atlases;Autopsy;Biological Assay;Biological Markers;biomarker development;Brain;BRAIN initiative;brain research;brain tissue;Cell Physiology;cell type;Cells;Chemicals;Classification Scheme;clinical phenotype;Cognitive;cohort;comorbidity;Data;Data Analyses;Dementia;design;Development;Diagnostic;Disease;disorder subtype;Eligibility Determination;Ensure;epigenomics;Evaluation;Experimental Models;Formalin;Fostering;Foundations;Functional disorder;Future;Genes;genetic information;genetic risk factor;Gliosis;Goals;Guidelines;Histologic;Human;human tissue;Image Analysis;Immunoassay;Individual;Inflammation;interest;Knowledge;Light;Maps;Measures;meetings;Methodology;Methods;Microglia;Microscopic;Modernization;Molecular;Molecular Analysis;Molecular Profiling;Molecular Target;Nerve Degeneration;Nervous System Disorder;Nervous System Trauma;neuroinflammation;Neurons;neuropathology;neurotoxicity;next generation;novel;Oxidative Stress;Paraffin Embedding;Pathogenesis;Pathologic;Pathology;Pathway interactions;Pattern;Peptides;Phase;phase 2 study;Phenotype;precision medicine;preservation;Prevalence;Proteins;Protocols documentation;Quality Control;repository;Research;Research Infrastructure;Research Personnel;research study;resilience;Resistance;Resolution;Resources;risk variant;Role;Sampling;Science;spelling;Stains;Stratification;Supporting Cell;Synapses;tau Proteins;Techniques;Technology;Testing;Therapeutic;therapeutic evaluation;Tissue Banks;Tissue Preservation;tissue resource;Tissue Sample;Tissues;transcriptomics;Universities;Washington;white matter;Work

PROJECT_TITLE: Novel platform for research brain banking and characterization using integrated traditional and quantitative analyses to promote precision neuropathology of Alzheimer's disease


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

PHR: PROJECT NARRATIVE (PROJECT 2) Alzheimer’s disease follows a highly stereotyped progression that differentially affects cell populations in the brain, and yet transcriptomic and epigenetic studies to date have largely focused on bulk tissue comprised of mixed cell populations, potentially obscuring key cell type-specific differences. The project proposed here will apply cutting edge single cell transcriptomic and epigenomic analysis in brain regions affected by Alzheimer’s disease (AD) pathology and across different stages of the disease to gain a dramatically higher resolution understanding of the cellular specificity of AD pathology and to identify signatures of the early pathogenesis of AD prior to the emergence of pathology. These data will help to understand differential vulnerability or resistance of specific cell types in AD, and push towards a mechanistic understanding of AD progression by identifying dysregulated gene networks within affected cell types.

PROJECT_TERMS: Adult;Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease pathology;Amyloid beta-Protein;amyloid pathology;Antibodies;Appearance;Autopsy;Biology;Brain;Brain region;brain tissue;Cell Nucleus;cell type;Cells;Chromatin;Classification;Clinical;Cognition;cohort;Communities;comorbidity;cost;Data;data platform;Data Set;Databases;Dementia;design;Disease;disease diagnosis;disease phenotype;Disease Progression;disorder subtype;drug discovery;Epigenetic Process;epigenomics;extracellular;follow-up;Functional disorder;Future;Gene Expression;Gene Expression Profile;gene network;Genes;Genetic;Genetic Transcription;Gliosis;Goals;hyperphosphorylated tau;Individual;insight;Link;Maps;Measurement;Memory;Methods;Methylation;misfolded protein;Modification;Molecular;multiple omics;Nerve Degeneration;Neurodegenerative Disorders;Neurofibrillary Tangles;neuron loss;neuropathology;next generation;normal aging;Nuclear;Pathogenesis;Pathologic;Pathology;Pathway interactions;Pattern;Phase;Phenotype;Population;Predisposition;Process;progressive neurodegeneration;Protocols documentation;Resistance;Resolution;Resources;RNA;Sampling;Severities;Severity of illness;single nucleus RNA-sequencing;Sorting;Specificity;Staging;Standardization;Stereotyping;Structure;success;Surveys;tau aggregation;tau Proteins;Techniques;Time;Tissues;transcriptomics

PROJECT_TITLE: Topographic, cell type and molecular pathway characterization ofAlzheimer's disease using single cell transcriptomics and epigenomics


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Cancer;Clinical Research;Data Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Ovarian Cancer;Prevention;Rare Diseases;Social Determinants of Health;Women's Health Research

ORG_CITY: MADISON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: PROJECT NARRATIVE New bioanalytical and computational technologies that can accurately identify cancer risks early are needed to improve cancer outcomes equitably. Here, we propose to develop an innovative spectrochemical liquid biopsy platform based on metasurface-enhanced mid-infrared absorption spectroscopy and machine-learning discrimination models. While the proposed research will optimize the novel imaging-based on-chip chemical fingerprinting technology using ovarian cancer samples, the developed diagnostic modality can be applied to detect a broad spectrum of disease-associated spectral patterns from biofluids in the future.

PI_NAMEs: YESILKOY, FILIZ  (contact)

PROGRAM_OFFICER_NAME: ANDERSON, AFROUZ AZARI

PROJECT_TERMS: absorption;Address;advanced analytics;Benign;Biological Markers;Biophotonics;Blood Tests;burden of illness;Cancer Biology;Cancer Control;Cancer Detection;Cancer Diagnostics;cancer health disparity;Cancer Patient;cancer risk;cancer type;chemical fingerprinting;Chemicals;Clinical;Clinical Management;cohort;Complex;cost;cost effective;Coupled;Data;data analysis pipeline;design;Detection;detection platform;Devices;Diagnosis;Diagnostic;diagnostic biomarker;Discrimination;Discrimination Learning;Disease;Early Diagnosis;Electromagnetics;Engineering;Equity;Female;Fingerprint;Functional disorder;Funding;Future;Goals;Grant;Health;Image;imaging approach;Imaging technology;improved;infrared spectroscopy;innovation;instrumentation;Label;Lasers;Light;Lipids;liquid biopsy;Machine Learning;machine learning method;machine learning model;Malignant neoplasm of ovary;Malignant Neoplasms;manufacture;Measurement;Medical;Methods;mid infrared spectrometry;Modality;Modeling;Molecular;mortality;multiple omics;nano;nanophotonic;Non-Invasive Cancer Detection;Non-Invasive Detection;novel;novel diagnostics;Nucleic Acids;Optics;Outcome;Pathologic;Patient Monitoring;Patients;Pattern;Pelvis;Performance;Peritoneal Fluid;photonics;Physiological;plasmonics;Population;Population Group;Population Heterogeneity;portability;Postmenopause;preclinical study;Proteins;Protocols documentation;quantum;Raman Spectrum Analysis;real world application;Recommendation;Research;Research Personnel;Retrieval;Sampling;screening;Screening for cancer;screening program;Serum;Signal Transduction;Socioeconomic Factors;spectrograph;Spectrometry;Spectrum Analysis;survival outcome;Survival Rate;Symptoms;System;Techniques;Technology;Temperature;Testing;Tissues;tool;United States National Institutes of Health;Validation

PROJECT_TITLE: Metasurface enhanced and machine learning aided spectrochemical liquid biopsy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-D(81)S]


PHR: PROJECT NARRATIVE (PROJECT 3) Alzheimer’s disease involves a predictable progression of neuropathological protein aggregation across brain regions. New highly multiplexed methods for fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), combined with detailed transcriptome-based classifications of cell types, offer a new high-resolution approach to understand selective vulnerability and resistance of different cell types to AD pathology. The goal of this project is to develop and apply highly multiplexed RNA combined with IHC methods to study quantitative changes in specific cell types with increasing AD severity, dysregulated molecular pathways in specific cell types, and relationships between pathological protein deposition and specific cell types in Alzheimer’s disease.

PI_NAMEs: CLOSE, JENNIE LEIGH (contact)

PROJECT_TERMS: Address;Adult;Affect;aged;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease pathology;Amyloid beta-Protein Precursor;Area;Brain;Brain region;brain tissue;Cell Nucleus;cell type;Cells;cellular targeting;cholinergic neuron;Classification;Clinical;cohort;Data;data acquisition;data analysis pipeline;Deposition;design;Disease Progression;epigenomics;excitatory neuron;Fluorescent in Situ Hybridization;Frequencies;Future;Gene Expression;Gene Expression Profiling;Generations;Genes;Genetic Transcription;Goals;Human;hyperphosphorylated tau;Immunohistochemistry;In Situ Hybridization;Link;Maps;Measures;Methods;Molecular;Nerve Degeneration;Neuroglia;neuropathology;Output;Pathogenesis;Pathologic;Pathway interactions;Phase;Population;Population Analysis;progressive neurodegeneration;Proliferating;protein aggregation;Protein Analysis;protein biomarkers;protein expression;Proteins;Resistance;Resolution;RNA;RNA analysis;Severities;Severity of illness;spatial relationship;Standardization;Subjects Selections;technology platform;Tissues;transcriptome;transcriptomics;Work

PROJECT_TITLE: Spatial analysis of regional, cell type and molecular hallmarks of Alzheimer's disease


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Immunotherapy;Inflammatory Bowel Disease;Nutrition

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: NARRATIVE Inflammatory diseases are often the consequence of inappropriate T cell effector activity or insufficient immune suppressive mechanisms. We have found that metabolic pathways are highly dynamic and exert strong effects on T cell differentiation and function. This study will explore metabolic vulnerabilities of inflammatory and regulatory T cells in methionine and nucleotide synthesis pathways that may be exploited to modulate T cell subsets in inflammatory bowel disease and other inflammatory disorders.

PI_NAMEs: RATHMELL, JEFFREY C. (contact)

PROGRAM_OFFICER_NAME: PERRIN, PETER J

PROJECT_TERMS: Amino Acids;Apoptosis;Autoimmune Diseases;Biological Assay;Carbon;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Cellular biology;Cellular Metabolic Process;conditional knockout;CRISPR screen;cytokine;Data;Dependence;deprivation;Diet;dietary;Disease;disease model;DNA Methylation;effector T cell;Enzymes;Equilibrium;Eragrostis;Fever;Folic Acid;Folic Acid Antagonists;Folic Acid Deficiency;Formates;Formyltetrahydrofolates;FOXP3 gene;Genetic;Glucose;glucose uptake;Goals;Guide RNA;histone methylation;Human;IL17 gene;Image;Immune;Immunity;Immunologics;Impairment;in vivo;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Interferon Type II;Interruption;Libraries;Measures;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Methionine;Methods;Methotrexate;microbiota;Mitochondria;Mus;nucleotide metabolism;Nucleotides;Nutrient;Nutrient availability;Oxidoreductase;Pathway interactions;Pattern;Pharmaceutical Preparations;Play;Positron-Emission Tomography;Production;programs;Purines;Reactive Oxygen Species;recruit;Regulation;Regulatory Pathway;Regulatory T-Lymphocyte;response;Role;Shapes;Signal Transduction;Site;T cell differentiation;T cell regulation;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;T-Lymphocyte Subsets;Temperature;Testing;Th1 Cells;Therapeutic;Tissues;Tracer;uptake;Work

PROJECT_TITLE: Exploiting metabolic vulnerabilities of CD4 T cell subsets to control inflammatory disease

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Lung;Physical Activity;Physical Rehabilitation;Rehabilitation;Rural Health;Social Determinants of Health;Telehealth

ORG_CITY: SPRINGFIELD

ORG_NAME: BAYSTATE MEDICAL CENTER, INC.

PHR: Narrative There is an urgent need to develop new strategies to improve uptake of cardiac and pulmonary rehabilitation. This is especially true in rural communities where resources are limited and transportation to center-based programs is a major barrier. We propose to examine whether implementing a stepped care model, in which patients have access to a hierarchy of interventions, is more effective than center-based programs.

PI_NAMEs: FRAENKEL, LIANA ;LINDENAUER, PETER KYLE (contact)

PROGRAM_OFFICER_NAME: TATAW-AYUKETAH, GLADYS OROCK

PROJECT_TERMS: Address;Adherence;arm;Cardiac rehabilitation;Cardiopulmonary rehabilitation;Caring;Certification;Community Health Aides;compare effectiveness;cost effectiveness;County;design;Education;education access;Educational Materials;Eligibility Determination;eligible participant;Enrollment;Evaluation;Event;Exercise;Exercise Tolerance;feasibility testing;feasibility trial;Frail Elderly;functional improvement;Goals;Health;Heart Diseases;Home;Hospitals;improved;individual patient;Intake;Intervention;Lung Diseases;Massachusetts;Measures;mobile application;Modeling;mortality;Outcome;Participant;participant enrollment;patient oriented;Patients;Persons;Process;programs;pulmonary rehabilitation;Quality of life;Randomized;Randomized, Controlled Trials;readmission rates;Rehabilitation Centers;Rehabilitation Nursing;Rehabilitation therapy;remote monitoring;Research;Resource Allocation;Resource-limited setting;Resources;Rural;rural area;Rural Community;rural counties;Self Management;Single-Blind Study;Site;Specialist;Specific qualifier value;standard of care;System;Technology;telerehabilitation;Training;Transportation;treatment as usual;trial comparing;uptake;virtual platform;Visit;Work

PROJECT_TITLE: Stepped care versus center-based cardiopulmonary rehabilitation for older frail adults living in rural MA

STUDY_SECTION: SSPT

STUDY_SECTION_NAME: NHLBI Single-Site and Pilot Clinical Trials Study Section[SSPT(OA)]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Machine Learning and Artificial Intelligence;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Prevention;Psychosis;Schizophrenia;Serious Mental Illness

ORG_CITY: Chicago

ORG_DEPT: PSYCHOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY

PHR: Narrative  Early detection of young people at clinical high risk for psychosis offers a critical opportunity for early intervention to improve the course of illness, and perhaps even prevent onset entirely. Current interview-based methods for psychosis risk detection lack specificity, and are only available in a handful of research centers in the United States. The proposed study aims to improve accessibility and broaden impact of high risk screening by testing brief computerized measures, ultimately able to be administered on the internet, and to improve prediction by focusing on tasks specific to underlying mechanisms driving emerging psychotic symptoms.

PI_NAMEs: MITTAL, VIJAY A (contact)

PROGRAM_OFFICER_NAME: MORRIS, SARAH ELIZABETH

PROJECT_TERMS: Address;American;Attenuated;Automobile Driving;Behavioral;Biological Markers;Clinical;clinical high risk for psychosis;clinical practice;cognitive testing;Collaborations;computerized;Computing Methodologies;design;Detection;Deterioration;Diagnosis;Dimensions;Early Diagnosis;Early identification;Early Intervention;follow-up;Foundations;Frequencies;functional decline;Functional disorder;functional outcomes;Generations;Goals;help-seeking behavior;high risk;high risk population;Human Resources;improved;Individual;Internet;Intervention Trial;Interview;Joints;Link;Longitudinal Studies;Machine Learning;machine learning classification;machine learning method;Measures;Methods;Modeling;neural;Neurobiology;new therapeutic target;next generation;online delivery;Outcome;Participant;Patient Self-Report;Performance;Persons;Population;Predictive Value;prevent;preventive intervention;Primary Prevention;Psychopathology;Psychoses;psychosis risk;psychotic symptoms;Public Health;Publishing;Recording of previous events;recruit;Research;Research Personnel;Risk;Role;Sample Size;screening;Secondary Prevention;Severities;Site;social;Specificity;Symptoms;System;Techniques;Test Result;Testing;Training;trait;Translating;United States;Work;Youth

PROJECT_TITLE: 2/5 CAPER Computerized assessment of psychosis risk


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Genetics;Infectious Diseases;Rare Diseases;Tickborne Diseases;Vector-Borne Diseases

ORG_CITY: ATLANTA

ORG_DEPT: PATHOLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative Tick-borne viruses, including the U.S.-endemic Powassan virus, cause a substantial and increasing burden of human illness, and more knowledge is needed about how they replicate and cause disease. This project will investigate a poorly-understood component of the Powassan virus life cycle, which is recombination within viral RNA molecules. This work will evaluate whether Powassan virus creates recombinant RNA molecules and whether there are differences in recombination when the virus replicates in ticks versus mammalian hosts, with the ultimate goal of understanding how recombination may contribute to disease and transmission in tick-borne viruses.

PI_NAMEs: LANGSJOEN, ROSE ;PIANTADOSI, ANNE L (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Anti-viral Agents;Arthropods;biobank;Biological;Biological Process;Black-legged Tick;Cell Line;cell type;Cells;Cessation of life;chronic infection;Data;deletion detection;design;detection method;Disease;Encephalitis;Event;Evolution;extracellular;Flavivirus;Flavivirus Infections;Foundations;Frequencies;Future;Genes;Genetic Recombination;Genetic Transcription;Genetic Variation;genomic locus;genomic RNA;Genomics;Geography;Goals;Helper Viruses;Human;human disease;Immune Evasion;Immune signaling;In Vitro;in vivo;Infection;insight;Investigation;Knowledge;Laboratories;Lead;Libraries;Life Cycle Stages;Location;Mammalian Cell;Maps;Measures;metagenomic sequencing;Methods;Morphologic artifacts;mosquito-borne;mouse model;Mus;Mutation;Nonstructural Protein;novel strategies;Nymph;Outcome;Pathogenesis;Patients;Pattern;Polymerase Gene;Population;Powassan virus;Predisposition;Preparation;Production;recombinant RNA;Recombinants;Reproducibility;Research Personnel;RNA;RNA replication;RNA Viruses;RNA-Directed RNA Polymerase;Role;Sampling;secondary analysis;Source;Spatial Distribution;Therapeutic;tick-borne flavivirus;tick-borne virus;Ticks;transmission process;United States;Untranslated RNA;Variant;vector tick;vector-borne;Viral;Viral Encephalitis;viral fitness;Viral Pathogenesis;viral RNA;Virion;Virus;Virus Diseases;Virus Replication;Work

PROJECT_TITLE: The role of RNA deletion and duplication events in Powassan virus pathogenesis and evolution


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Project Narrative Radical S-adenosyl-L-methionine enzymes are found in all kingdoms of life and perform reactions that underpin human health, disease, and metabolism. We propose to study the mechanisms of these reactions, focusing on the central role of organometallic intermediates. Our approach is to investigate structurally and functionally faithful model complexes of these reactive species to elucidate their roles in catalysis.

PI_NAMEs: SUESS, DANIEL LEIF MIGDOW (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TITLE: Modeling the Organometallic Chemistry of Radical S-adenosylmethionine Enzymes

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Pediatric;Regenerative Medicine

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative This study aims to reveal the physiological triggers of cardiac regenerative potential loss during postnatal growth. This will provide novel insights into organ regeneration, possibly suggesting new targets and strategies to treat heart failure.

PI_NAMEs: HUANG, GUO  (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, LISA

PROJECT_TERMS: Acute;Adrenergic Receptor;Adult;Animals;Applications Grants;B-Cell Activation;B-Cell Lymphoma 6 Protein;BCL6 gene;Birth;Cardiac;Cardiac Myocytes;cardiac regeneration;cardiac repair;Cell Cycle;Cell Cycle Arrest;Cell Cycle Regulation;Chemicals;Clinical Treatment;coronary fibrosis;Data;Development;differential expression;Evolution;experimental study;Genes;Genetic;Genetic Models;Growth;Heart;heart dimension/size;Heart Diseases;Heart failure;heart function;Heterocephalus;hormonal signals;Human;Image;improved;inhibitor;Injury;injury and repair;insight;ischemic injury;Knowledge;Light;Loss of Heterozygosity;Mammals;Methods;Microscopy;Mole Rats;mortality;mouse genetics;Mus;mutant;Mutant Strains Mice;Myocardial Infarction;myocardial injury;Nerve;Newborn Infant;novel;organ regeneration;Pathway interactions;Patients;Phenotype;Phylogeny;Physiological;postnatal;Process;Proliferating;Publishing;Receptor Activation;regeneration potential;Regenerative capacity;regenerative repair;Regulation;repaired;Reporting;Repression;response to injury;Rodent;Role;Science;self-renewal;Signal Transduction;Stains;synergism;Thermogenesis;Thyroid Hormone Receptor;Thyroid Hormones;Tissues;transcription factor;Transcription Repressor;transcriptome sequencing;treatment strategy;United States;Up-Regulation;Viral Vector;Weight;Withdrawal;Work;Zebrafish

PROJECT_TITLE: Genetic circuitry governing heart growth and repair

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Although the role of p53 in tumor suppression is indisputable, it remains a daunting task how to target this pathway for cancer therapy. Like Mdm2, the VPRBP-USP2 axis is critical for repressing p53 function in human cancers; unlike Mdm2, the VPRBP-USP2 axis acts as a master regulator of PD-L1 expression in a p53-independnet manner. By using both tissue culture and animal models, we will dissect the mechanisms of both USP2 and VPRBP in regulating p53–mediated tumor suppression as well as their effects in anti-tumor immunity.

PI_NAMEs: GU, WEI  (contact)

PROGRAM_OFFICER_NAME: MAAS, STEFAN

PROJECT_TERMS: Acetylation;Animal Model;anti-PD-1;anti-PD1 antibodies;Antibodies;Antibody Therapy;antitumor effect;Attenuated;attenuation;C-terminal;cancer cell;Cancer Patient;cancer therapy;Cell Survival;Cell-Mediated Cytolysis;Clinical Data;Clinical Research;Cytotoxic T-Lymphocytes;Data;Development;dosage;Dose Limiting;Event;gene repression;Genes;Genetic Transcription;Human;Immune;immune checkpoint;immunodeficiency;Immunologic Surveillance;improved;In Vitro;in vivo;inhibitor;insight;knock-down;Knock-out;Ligands;Malignant Neoplasms;MDM2 gene;Mediating;Molecular;mouse model;Mus;Mutate;neoplastic cell;Normal tissue morphology;novel;Nude Mice;overexpression;Pathway interactions;patient stratification;Patients;Peptides;prevent;Probability;programmed cell death ligand 1;programmed cell death protein 1;receptor;Repression;Role;side effect;Signal Transduction;small molecule inhibitor;success;T-Cell Activation;T-Lymphocyte;Therapeutic;therapeutic target;therapeutically effective;Thinking;tissue culture;Toxic effect;TP53 gene;tumor;tumor growth;Tumor Immunity;Tumor Suppression;tumorigenesis;ubiquitin isopeptidase;ubiquitin-protein ligase;Up-Regulation

PROJECT_TITLE: Co-regulation of p53 and PD-L1 by the VPRBP-USP2 axis in transcription and ubiquitylation

STUDY_SECTION: MONC

STUDY_SECTION_NAME: Molecular Oncogenesis Study Section[MONC]


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Fragile X Syndrome;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: MANHATTAN

ORG_NAME: KANSAS STATE UNIVERSITY

ORG_STATE: KS

PHR: Project Narrative This project examines the role of the frontal cortex in Fmr1 Knock outs (model of Fragile X) during cognitive flexibility. It is important to understand how altered neural function and hyperexcitability impact cognition. By recording neural activity at the cellular level and with local field potentials, it allows for translational comparisons to human neural data.

PI_NAMEs: PLAKKE ANDERSON, BETHANY  (contact)

PROGRAM_OFFICER_NAME: RANGEL GOMEZ, MAURICIO

PROJECT_TERMS: Affect;Animals;Anterior;Attention;autism spectrum disorder;behavioral phenotyping;Brain;Categories;cingulate cortex;Cognition;Cognitive;Cognitive deficits;cognitive function;cognitive task;Cues;Data;developmental disease;Dimensions;Electroencephalography;Exhibits;Face;Female;flexibility;Fragile X Syndrome;Frequencies;frontal lobe;Future;Genetic;Genetic Models;Genetic Risk;Glutamate Receptor;Goals;Human;human data;Impairment;improved;in vivo;Individual;individuals with autism spectrum disorder;Intellectual functioning disability;Interneurons;Knock-out;Learning;Left;male;Measures;Medial;Methods;Mission;Modeling;National Institute of Child Health and Human Development;neural;Neurodevelopmental Disorder;neurophysiology;Neurophysiology - biologic function;Outcome;Pathology;Perception;Performance;Persons;Phase;Prefrontal Cortex;Publications;Pyramidal Cells;Rattus;receptor function;Research Personnel;Reversal Learning;Role;Rotation;Side;Stimulus;Syndrome;Time;touchscreen;Training;Valproic Acid;Work

PROJECT_TITLE: Understanding the role of the frontal cortex during cognitive flexibility in Fmr1 knock outs

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;HIV/AIDS;Hypertension;Infectious Diseases;Prevention;Primary Health Care

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative This hybrid clinical-implementation study will be conducted in 3 phases: 1) a pre-implementation phase using CFIR to determine the barriers and facilitators of the adoption of TASSH and to develop the practice facilitation (PF) intervention; 2) an implementation phase which will compare, in a cluster RCT of 30 HIV clinics among 960 HIV+ patients, the effect of the PF intervention vs. a self-directed condition (i.e. receipt of information for implementation of HTN control without PF) on BP reduction; and 3) a post-implementation phase using RE- AIM to compare the effect of PF vs. self-directed condition on adoption and sustainability of TASSH. The PF intervention will comprise an advisory board of key stakeholders who will provide leadership support for TASSH adaptation and its implementation; practice facilitators, and trained nurses, who will deliver TASSH.

PI_NAMEs: EZECHI, OLIVER CHUKWUJEKWU;IWELUNMOR, JULIET ;OGEDEGBE, OLUGBENGA G. (contact)

PROGRAM_OFFICER_NAME: REDMOND, NICOLE

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Acute;Address;Adopted;Adoption;Africa;antiretroviral therapy;blood pressure reduction;burden of illness;Caring;Characteristics;Chronic Care;Climate;Clinic;Clinical;Clinical effectiveness;Collaborations;Consolidated Framework for Implementation Research;Counseling;Country;Data;design;Effectiveness;effectiveness/implementation design;evidence base;Evidence based intervention;experience;Feedback;General Population;Ghana;Health;Health Insurance;Healthcare;Healthcare Systems;HIV;Hybrids;Hypertension;hypertension control;implementation framework;implementation process;implementation strategy;implementation study;Income;Infrastructure;Insurance Coverage;Intervention;Knowledge;knowledge base;Leadership;Life Style;low and middle-income countries;Maintenance;Mediator;Medical Research;Modeling;Morbidity - disease rate;mortality;New York;Nigeria;Nigerian;Nurses;Patients;Performance;personalized approach;Persons;Pharmaceutical Preparations;Phase;Physicians;post implementation;pragmatic implementation;Prevalence;prevent;primary care practice;Primary Health Care;primary outcome;Probability;Protocols documentation;Qualitative Methods;Randomized;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Reporting;Research;research to practice;Risk;Risk Assessment;Role;routine care;routine practice;secondary outcome;Self Direction;System;system-level barriers;Testing;Titrations;Training;Translating;Universities;uptake

PROJECT_TITLE: Integration of Hypertension Management into HIV Care in Nigeria: A Task Strengthening Strategy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HDM-G(91)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: BOSTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: TUFTS UNIVERSITY BOSTON

ORG_STATE: MA

PHR: Project Narrative Vibrio cholerae is a globally important pathogen and the burden of cholera is estimated to reach several million cases annually. V. cholerae virulence depends on a cell-cell communication process called quorum sensing that controls the timing of production and release of virulence factors and the formation of biofilms. The investigations proposed here will expand our understanding of how quorum sensing controls virulence in this important pathogen. In addition, this study will facilitate the development of synthetic strategies for controlling V. cholerae virulence and could have significant ramifications for improving human health.

PI_NAMEs: NG, WAI-LEUNG  (contact)

PROGRAM_OFFICER_NAME: ZEITUNI, AMIR E

PROJECT_TERMS: Affect;Animals;Bacteria;Behavior;Biochemical;Biological Assay;Cell Communication;Cell Physiology;Cell Signaling Process;Cells;Chemicals;Cholera;Chromatography;combat;Communicable Diseases;Competence;Cyclic AMP;Cyclic GMP;Data;design;Detection;Development;Dinucleoside Phosphates;Disease;Environment;environmental stressor;Ethanolamines;follow-up;Gastrointestinal tract structure;Gene Expression;Gene Expression Regulation;gene function;Genes;Genetic;Goals;gut colonization;Health;host colonization;Human;human pathogen;improved;Infection;Investigation;Knowledge;Life Cycle Stages;Ligand Binding;Ligands;Link;Mediator;Metabolism;Microbial Biofilms;Molecular;mutant;Natural Immunity;novel;novel therapeutics;pandemic disease;pathogen;Pathogenesis;Pathway interactions;Periodicity;Phosphotransferases;Physiological;Population;Predisposition;Process;Production;protein-histidine kinase;Proteins;quorum sensing;receptor;Regulon;Research;response;Role;Second Messenger Systems;Sensory;Signal Pathway;Signal Transduction;Signaling Molecule;Structural Models;Structure;System;Techniques;Time;trait;Translating;Vibrio cholerae;Virulence;Virulence Factors;virulence gene;whole animal imaging;Work;X-Ray Crystallography

PROJECT_TITLE: Signaling Mechanisms in Vibrio Cholerae Parallel Quorum Sensing Pathways

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Clinical Research;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Human Genome;Pediatric;Rare Diseases

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PUBLIC HEALTH RELEVANCE This project uses animal models of human disease combined with genomic rare variant analysis in patients with congenital heart defects to identify the mechanisms by which a group of heart defects develop. These results will increase our understanding of why heart defects occur and why they are so variable.

PI_NAMEs: WARE, STEPHANIE M (contact)

PROGRAM_OFFICER_NAME: LI, HUIQING

PROJECT_TERMS: Actomyosin;Address;Animal Model;Apical;Binding;biobank;Biological Assay;cardiogenesis;Cause of Death;Cell Lineage;cell motility;Cell Polarity;Cells;Child;cohort;Congenital Abnormality;congenital heart abnormality;Congenital Heart Defects;constriction;Cytoskeleton;Data;Defect;Development;Developmental Biology;developmental genetics;disease phenotype;Disease susceptibility;Embryonic Heart;Etiology;Exhibits;exome;exome sequencing;Family;Frequencies;functional genomics;Genes;Genetic;genetic architecture;Genetic Epistasis;Genetic Predisposition to Disease;genetic testing;genetic variant;genome sequencing;genome wide association study;Genomics;heart defect;Heterozygote;Human;human disease;Human Genetics;human genomics;human model;Immunoprecipitation;improved;In Vitro;in vivo;Indiana;Investigation;Knowledge;Lead;Link;Mass Spectrum Analysis;member;mouse model;Movement;Mus;Mutate;Mutation;novel;Outcome;Pathway interactions;Patients;Pediatric Cardiac Genomics Consortium;Penetrance;Phenocopy;Phenotype;planar cell polarity;Predisposition;Prognosis;protein protein interaction;Proteins;public health relevance;rare variant;Rho-associated kinase;risk prediction;Role;Shapes;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Technology;Testing;Tissues;transcriptome sequencing;Translating;Variant;Ventricular Septal Defects;whole genome;Xenopus

PROJECT_TITLE: Developmental and genetic function of SHROOM3

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


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

ORG_CITY: LA JOLLA

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative BDNF gene therapy for Alzheimer’s disease is neuroprotective and improves cognitive function, but delivery by direct brain injection is invasive and treats only a small percentage of cortex. Intrathecal infusion of AAV9-BDNF gene therapy is simple, minimally invasive, and broadly treats the entire cerebral cortex when combined with two hours of Trendelenburg positioning. This novel approach could enhance the safety and efficacy of gene therapy clinical trials for Alzheimer’s disease and other neurological disorders, and could support the discovery of new preclinical gene therapies for Alzheimer’s disease.

PI_NAMEs: CASTLE, MICHAEL ;TUSZYNSKI, MARK H. (contact)

PROGRAM_OFFICER_NAME: GROTHAUS, PAUL G

PROJECT_TERMS: adeno-associated viral vector;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease therapy;Amyloid;Amyloid deposition;Anatomy;Antibody Response;Behavioral;Brain;Brain region;Brain-Derived Neurotrophic Factor;Cells;Cellular biology;cellular transduction;Cerebral cortex;Cerebrospinal Fluid;Clinical;clinical translation;Clinical Treatment;Clinical Trials;cognitive function;Dependovirus;design;disease model;Doctor of Medicine;Doctor of Philosophy;Dose;enhancing factor;entorhinal cortex;experience;experimental study;foot;Gene Expression;gene therapy;gene therapy clinical trial;Gene Transduction Agent;Gene Transfer;Gliosis;Growth Factor;Head;Hippocampus;Hour;Human;Immune response;improved;Infusion procedures;Injections;Intravenous;Learning;Macaca mulatta;Mediating;Memory;Methods;minimally invasive;Molecular Biology;Mus;Nerve Degeneration;Nervous System;Nervous System Disorder;Neuroglia;neuron loss;Neurons;neuroprotection;next generation;nonhuman primate;novel;novel strategies;Outcome;Pathologic;Patients;Peripheral;pre-clinical;Pre-Clinical Model;preclinical development;Preclinical Testing;preservation;prevent;Principal Investigator;Production;promoter;Qualifying;Rattus;Reporting;Rodent;Rodent Diseases;Safety;safety testing;Serotyping;Serum;side effect;Specificity;Spinal Cord;Supination;Synapses;Synaptic plasticity;targeted treatment;tau Proteins;Testing;therapeutic evaluation;Tissues;Transgenic Mice;translational potential;treatment duration;treatment effect;Treatment Efficacy;Trendelenburg Position;Validation

PROJECT_TITLE: Improved Intrathecal BDNF Gene Therapy for Alzheimer's Disease

STUDY_SECTION: CDIN

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


ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: PROJECT NARRATIVE Biomolecular condensates mediate crucial cellular functions and are linked with neurodegeneration and cancer. In this project, the quantitative, mechanistic studies of condensates and other paradigms of molecular recognition will not only advance fundamental understanding in biology but also yield opportunities, including new targets and new pathways, for designing therapies.

PI_NAMEs: ZHOU, HUAN-XIANG  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Address;Aging;Behavior;Binding;Binding Proteins;Biological Phenomena;Biology;Cell Physiology;Cellular biology;Complex;Developmental Biology;Disease;Equilibrium;Foundations;Funding;Goals;Link;Lipids;macromolecule;Malignant Neoplasms;Measures;Mediating;Membrane;Modeling;Molecular;Molecular Biology;Molecular Conformation;molecular recognition;Nerve Degeneration;Pathway interactions;Phase;Physical condensation;Physics;Point Mutation;Post-Translational Protein Processing;Property;Proteins;Research;therapy design

PROJECT_TITLE: Quantitative, Mechanistic Studies of Biomolecular Recognition

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Childhood Injury;Clinical Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Prevention;Sleep Research;Suicide

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative Despite the enormous public health problem of suicide among adolescents, little progress has been made toward improving assessment and prevention for this vulnerable group. We will conduct a prospective, longitudinal study to examine the near-term temporal associations between within-person fluctuations in sleep disturbance, dysregulation in affective, cognitive and arousal-related systems, and changes in suicidality over time in ultra-high risk adolescents. Critically, since sleep is a modifiable risk factor, our findings hold great promise to inform the development or modification of existing sleep/mental health interventions to lower suicide risk.

PI_NAMEs: FRANZEN, PETER L;GOLDSTEIN, TINA R (contact)

PROGRAM_OFFICER_NAME: MURPHY, ERIC ROUSSEAU

PROJECT_TERMS: actigraphy;Adolescence;Adolescent;Affect;Affective;Age;age effect;age group;American;Arousal;Attention;Behavior;Behavioral;behavioral impairment;Behavioral inhibition;Biological;biopsychosocial;Cardiac;Cause of Death;Cellular Phone;Clinic;Clinical;clinical infrastructure;Cognitive;cognitive control;Complex;cost;Data;Data Reporting;Day Care;design;Development;Developmental Process;Diagnostic;diaries;Dimensions;Distal;Electrocardiogram;Emotional;Enrollment;Event;Feeling suicidal;Frequencies;Gender;heart rate variability;high risk;high risk population;high-risk adolescents;Impairment;improved;Impulsivity;innovation;Intervention;Learning;Link;longitudinal, prospective study;Machine Learning;Measures;Mediating;Mental disorders;Mental Health;Methods;Modeling;modifiable risk;Modification;mood symptom;Moods;outpatient programs;Outpatients;Participant;Pathway interactions;Patient Self-Report;Pattern;Persons;Physiology;poor sleep;Prevention;Prevention strategy;Process;programs;prospective;Psychopathology;psychosocial;Public Health;Regulation;Reporting;Research;Research Domain Criteria;Research Infrastructure;Rewards;Risk;Risk Assessment;Risk Factors;Role;Sampling;Shapes;Sleep;sleep behavior;Sleep Disorders;Sleep disturbances;sleep health;sleep quality;sleep regulation;substance use;suicidal;suicidal behavior;suicidal risk;Suicide;Suicide attempt;System;Task Performances;Techniques;Time;Vulnerable Populations;Work;Youth

PROJECT_TITLE: The Role of Sleep Health in Proximal Suicide Risk among Ultra-High Risk Adolescents


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_DEPT: NEUROLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: We propose to determine neuroprotective mechanism for microglial autophagy in the clearance of amyloid A-beta and constraining excessive neuroinflammation using Alzheimer's disease mouse models

PI_NAMEs: YUE, ZHENYU  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: abeta accumulation;Alleles;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's Disease Pathway;Amyloid;Amyloid beta-Protein;Animal Disease Models;Anti-Inflammatory Agents;Apoptotic;Autophagocytosis;Behavior;Brain;brain cell;Cell Nucleus;cell type;Cells;cytokine;Disease;Disease associated microglia;Disease Progression;EPHA1 gene;FRAP1 gene;Functional disorder;gender difference;Genes;genetic risk factor;genetic variant;genome wide association study;glial activation;Gliosis;Goals;Homeostasis;Human;Human Genetics;Immune;Immune system;Immunity;Immunologic Surveillance;Inflammasome;Inflammation;Inflammatory;insight;Late Onset Alzheimer Disease;Link;Lysosomes;Mediating;Metabolic;metabolic fitness;Metabolic stress;Microglia;Morphology;mouse model;neuroinflammation;Neurons;neuropathology;neuroprotection;neurotoxicity;new therapeutic target;pathogen;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Peripheral;phagocytosis receptor;Phenocopy;Play;Prefrontal Cortex;prevent;receptor;response to injury;restraint;Risk;Role;single-cell RNA sequencing;Surveys;Synapses;Testing;transcriptomics;TREM2 gene;Up-Regulation;Variant

PROJECT_TITLE: Determining the neuroprotective mechanism for microglial autophagy in Alzheimer's disease