NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Ovarian Cancer;Rare Diseases;Women's Health Research

PHR: Our recent clinical and experimental work has for the first time revealed that UBR5, an E3 ubiquitin ligase with novel protooncogene properties, profoundly promotes breast cancer growth and metastasis at least in a major part through regulating the expression of two important targets: CDC73 (a tumor suppressor) and PD-L1 (an immune checkpoint regulator). The proposed project will further expand and deepen the exploration of underlying cellular and molecular mechanisms whereby UBR5 controls CDC73’s crucial activities and the broad IFN--mediated signaling in cancer cells. The results will lay the groundwork for developing innovative and efficacious therapeutic strategies for TNBC by targeting UBR5 and its downstream signaling pathways.

PI_NAMEs: MA, XIAOJING  (contact);ZHOU, PENGBO

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Binding;Biochemical;Biology;BRCA1 Mutation;C-terminal;cancer cell;Cancer Patient;Cartoons;CD8-Positive T-Lymphocytes;Cells;Characteristics;chemokine;chemotherapy;Chimera organism;Chromatin;Cisplatin;Clinical;Combination immunotherapy;Complex;CTLA4 gene;Cytotoxic T-Lymphocytes;Data;Development;DNA Sequence Alteration;docetaxel;experimental study;Gene Amplification;Gene Expression Profile;Genes;Genetic Transcription;Genetically Engineered Mouse;genome-wide;Growth;Human;immune checkpoint;Immune checkpoint inhibitor;immunoregulation;Immunosuppression;In Vitro;in vivo;innovation;Interferons;Intervention;IRF1 gene;Lesion;Macrophage;Malignant - descriptor;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant neoplasm of prostate;Malignant Neoplasms;mammary epithelium;Mammary Neoplasms;Mediating;Modeling;Molecular;multicatalytic endopeptidase complex;Mutation;Neoplasm Metastasis;neoplastic cell;Nodule;novel;novel therapeutics;Oncogenes;Outcome Study;overexpression;Pathway interactions;pharmacologic;Play;Poly A;Polyubiquitination;posttranscriptional;PRKR gene;programmed cell death ligand 1;programmed cell death protein 1;programs;Property;protein degradation;Proteins;Proto-Oncogenes;prototype;recruit;Regulation;RNA Polymerase II;Role;Science;Signal Induction;Signal Pathway;Signal Transduction;Site;STAT1 gene;Structure-Activity Relationship;Testing;Therapeutic;Therapeutic Intervention;therapy resistant;Time;transcription factor;Transcriptional Regulation;transcriptome sequencing;triple-negative invasive breast carcinoma;tumor;Tumor Escape;tumor growth;tumor microenvironment;Tumor Suppressor Proteins;Tumor-Derived;tumorigenesis;tumorigenic;ubiquitin-protein ligase;Validation;Work

PROJECT_TITLE: UBR5's mechanisms of action in tumorigenesis and immunoregulation

STUDY_SECTION: TTT

STUDY_SECTION_NAME: Transplantation, Tolerance, and Tumor Immunology Study Section[TTT]


ADMINISTERING_IC: EB

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Women's Health Research

ORG_CITY: Chicago

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE  This project aims to bring the advancements in multi-high-b-value diffusion-weighted imaging (DWI) to the breast to enable a comprehensive characterization of breast tissue. This will be achieved by developing a novel, distortion-resilient, and time-efficient diffusion pulse sequence – Steer-PROP for breast DWI (SPREAD) – and an integrated multi-modal MRI analysis framework – TERMINAL – for the breast. These important tools will enable DWI acquisition with a full b-value spectrum and DWI analysis for assessing malignancy and evaluating treatment response in breast cancer.

PI_NAMEs: KARAMAN, MUGE M (contact)

PROGRAM_OFFICER_NAME: BARRY, ROBERT LEO II

PROJECT_TERMS: Adjuvant Chemotherapy;Base Sequence;Benign;Biological;Biopsy;Blood Vessels;Breast;Breast Cancer Patient;breast imaging;breast lesion;Breast Magnetic Resonance Imaging;Cell Density;Cells;Cellularity;Classification;Clinical;Communities;contrast enhanced;Contrast Media;density;design;Diffusion;Diffusion Magnetic Resonance Imaging;Disease;Echo-Planar Imaging;Goals;Heterogeneity;Histopathology;Image;Imaging Device;interest;International;Lesion;Link;Magnetic Resonance Imaging;Malignant - descriptor;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Gland Parenchyma;Mammary Neoplasms;Measurement;Measures;Modeling;Morphologic artifacts;Motion;Motivation;multimodality;Neoadjuvant Therapy;non-Gaussian model;novel;Pathologic;Phase;Physiologic pulse;Physiological;predicting response;Prediction of Response to Therapy;Property;Protocols documentation;prototype;Publications;Research;resilience;Resolution;Scanning;Structure;Techniques;Texture;Time;Tissues;tool;treatment response;Walking;working group

PROJECT_TITLE: Comprehensive Characterization of Breast Tissue Using Multi-modal MRI


ADMINISTERING_IC: MH

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PI_NAMEs: MONOSOV, ILYA E. (contact)

PROJECT_TERMS: Adaptive Behaviors;Agonist;Algorithms;Anatomy;Animal Model;Animals;Anxiety;Area;Axon;Behavior;Behavior Control;Behavioral;Brain;brain control;Brain region;Clinical;Collaborations;Computer Analysis;Data;Decision Making;Dedications;design;Desire for food;Development;Electrophysiology (science);Event;expectation;experimental study;Grant;Histologic;Human;Image Analysis;in vivo;Incentives;information processing;Insula of Reil;Internal Capsule;Laboratories;Magnetic Resonance Imaging;maladaptive behavior;Maps;Measures;Mediating;Mental disorders;Methods;Monkeys;motivated behavior;Muscimol;Negative Reinforcements;neural;neural circuit;Neurobiology;Neurons;neurotransmission;nonhuman primate;novel;novel therapeutics;Obsessive-Compulsive Disorder;optogenetics;Outcome;Pathology;Pathway interactions;Patients;Physiology;Play;Prefrontal Cortex;Procedures;Process;Property;Psyche structure;Psychological reinforcement;Publications;Rewards;Risk;Role;Symptoms;therapy development;Uncertainty;willingness;Work

PROJECT_TITLE: Physiology and information processing of the OCD circuit


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

PI_NAMEs: PHILLIPS, MARY LOUISE (contact)

PROJECT_TERMS: Adopted;Age;Anatomy;Anisotropy;Anterior;Behavior;behavioral impairment;Characteristics;Choice Behavior;cingulate cortex;Clinical assessments;Clinical Treatment;Clomipramine;Cognition;Cognitive;Collaborations;Computer Models;Corpus Callosum;Corpus striatum structure;Cues;Data;Data Analyses;density;Diffusion;Dimensions;Disease;Dorsal;Evaluation;Fiber;flexibility;Functional Magnetic Resonance Imaging;Gender;Goals;Image;indexing;Individual;Individual Differences;Insula of Reil;Internal Capsule;Intervention;Lead;Limb structure;Link;Location;Measures;Mediating;Methods;Motor;neural;neural circuit;neural network;Neural Pathways;Neurites;Neuroanatomy;neuroregulation;novel;Outcome;Participant;Pattern;Pharmaceutical Preparations;Phase;Physiology;Prefrontal Cortex;Probability;Radial;Recording of previous events;recruit;response;Rewards;Selective Serotonin Reuptake Inhibitor;Severities;Site;Structure;Symptoms;Task Performances;Therapeutic;tractography;white matter;Work

PROJECT_TITLE: Linking persistent avoidance with abnormalities in the OCD neural network


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Breast Cancer;Cancer;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Contraception/Reproduction;Dementia;Estrogen;Menopause;Natural Products;Neurodegenerative;Neurosciences;Prevention;Women's Health Research

ORG_CITY: TUCSON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Women are at greater lifetime risk for Alzheimer’s disease (AD). One potential contributing factor is the midlife neuroendocrine aging transition. PhytoSERM addresses a critical unmet need in women’s health for an alternative hormone therapy that is both safe and efficacious for menopausal symptoms and to reduce risk of AD later in life.

PI_NAMEs: BRINTON, ROBERTA EILEEN (contact);HERNANDEZ, GERSON DAVID;MOSCONI, LISA

PROGRAM_OFFICER_NAME: RYAN, LAURIE M

PROJECT_TERMS: 3 year old;Address;Age;Age Years;age-related disease;aged;Aging;Alternative Health;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer’s disease biomarker;American;arterial spin labeling;blood-based biomarker;Brain;brain metabolism;Brain region;brain volume;Breast;Breast Cancer Risk Factor;Cell Proliferation;Cerebrovascular Circulation;Cerebrum;Clinical;clinical development;clinical efficacy;Clinical Research;Clinical Trials;Clinical Trials Cooperative Group;Cognition;cognitive function;critical period;daidzein;Development;Diffusion;Diffusion Magnetic Resonance Imaging;disability;Disease;Double-Blind Method;Drug Kinetics;effective intervention;effective therapy;efficacy evaluation;Endocrine;equol;Estrogen Receptor 2;Estrogen Therapy;estrogenic;Estrogens;Exhibits;experience;Female;Fiber;fluorodeoxyglucose;fluorodeoxyglucose positron emission tomography;Formulation;Frequencies;Fright;Functional Magnetic Resonance Imaging;Genistein;Glucose;glucose metabolism;Goals;gray matter;Health;hormone therapy;Hormones;Hot flushes;Image;Inflammatory;innovation;Intervention;Label;late life;Legal patent;Life;lifetime risk;Magnetic Resonance Imaging;Malignant Breast Neoplasm;Mammary Gland Parenchyma;manufacture;manufacturing quality;Measures;Memory;menopausal aging;Menopausal Symptom;Menopause;Menstruation;Metabolic;metabolic rate;middle age;mood symptom;National Institute on Aging;Neurologic;Neurologic Symptoms;Neurosecretory Systems;Outcome;Participant;Perimenopause;Personal Satisfaction;Pharmaceutical Preparations;Phase;Phase I Clinical Trials;Phase II Clinical Trials;Phenotype;Phytoestrogens;Placebo Control;Placebos;Postmenopause;pre-clinical;preclinical development;prevent;Prevention strategy;Process;Proliferating;Quality Control;Randomized;rational design;reproductive;Research Support;Rest;Risk;Risk Reduction;Safety;Severities;sleep quality;stability testing;Tissues;Translating;Translations;treatment strategy;Uterus;vasomotor symptoms;white matter;Woman;Women's Health

PROJECT_TITLE: PhytoSERM Efficacy to Prevent Menopause Associated Decline in Brain Metabolism and Cognition: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Clinical Trial


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Clinical Research;Mental Health;Neurosciences;Patient Safety;Prevention

PI_NAMEs: BAKER, JUSTIN T (contact)

PROJECT_TERMS: Affect;Aftercare;Anisotropy;Anterior;Behavior;Behavioral;behavioral impairment;Brain;burden of illness;Clinical;Clinical assessments;clinical heterogeneity;conventional therapy;Corpus Callosum;Corpus striatum structure;Cues;Data;Data Collection;density;Devices;Diffusion Magnetic Resonance Imaging;digital phenotyping;Dimensions;Early treatment;efficacious treatment;experience;Fiber;flexibility;Functional Magnetic Resonance Imaging;Funding;Goals;Hospitals;imaging biomarker;indexing;Individual;Insula of Reil;Internal Capsule;Intervention;Limb structure;Link;Magnetic Resonance Imaging;Measures;Medication Management;member;National Institute of Mental Health;neural circuit;neural network;Neurites;Outcome;Participant;Pattern;Performance;Phase;Prediction of Response to Therapy;Prevention therapy;Probability;psychopharmacologic;Radial;Reporting;Residential Treatment;response;Rewards;Sampling;Serial Magnetic Resonance Imaging;Severities;Signal Transduction;standard of care;Structure;Symptoms;Testing;Therapeutic;Time;trait;Uncertainty;Variant;Visit

PROJECT_TITLE: Modulation of the OCD neural network by conventional treatment


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Neurosciences;Precision Medicine

PI_NAMEs: RASMUSSEN, STEVEN A (contact)

PROJECT_TERMS: Acute;Affect;Algorithms;analytical method;Anatomy;Anterior;Area;Axon;Behavioral;capsule;cingulotomy;clinical outcome measures;Crossover Design;design;Diffusion;Disease;Double-Blind Method;efficacy study;electric field;Electrophysiology (science);Feasibility Studies;feasibility testing;Fiber;Focused Ultrasound;Functional Imaging;Functional Magnetic Resonance Imaging;Funding;Goals;Human;Image;imaging study;Implant;improved;Individual;Intervention;Knowledge;Lasers;Lesion;Limb structure;Magnetic Resonance Imaging;Measures;Methodology;Modeling;Negative Finding;neural circuit;neuroregulation;novel;Outcome Measure;Patients;personalized approach;Positioning Attribute;potential biomarker;Prediction of Response to Therapy;Primates;Refractory;Resolution;Rest;Running;Safety;safety study;Scanning;Site;System;Testing;Therapeutic Effect;Time;Treatment outcome;treatment response;Uncertainty;white matter

PROJECT_TITLE: Neuromodulation of OCD Circuitry


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_CITY: CINCINNATI

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: PROJECT NARATIVE The proposed research is relevant to public health because understanding the dynamics and regulatory mechanisms of guanosine signaling in the brain during ischemia is expected to advance knowledge of the brains immediate neuroprotection response and provide critical information on potential therapeutic targets for ischemia. Methods to monitor rapid guanosine signaling at the local site of ischemia during injury are lacking and we will bridge this critical gap by developing new platforms which combine millisecond-to-second guanosine recording with microfluidic focal brain stimulation. Thus, this proposal is relevant to part of the NIH’s mission that pertains to fostering fundamental creative discoveries and innovative research strategies as a basis for protecting and improving health.

PI_NAMEs: ROSS, ASHLEY E (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TITLE: Monitoring rapid guanosine signaling during ischemia

STUDY_SECTION: BNVT

STUDY_SECTION_NAME: Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section[BNVT]


PI_NAMEs: YENDIKI, ANASTASIA  (contact)

PROJECT_TERMS: Adopted;Affect;Aftercare;analysis pipeline;anatomical tracer;anatomical tracing;Anatomy;Anterior;Autopsy;Axon;Brain;brain circuitry;Brain Mapping;brain pathway;cingulate cortex;Collaborations;Corpus Callosum;Corpus striatum structure;Data;data acquisition;Data Analyses;data analysis pipeline;data integration;design;Development;Diffusion;Diffusion Magnetic Resonance Imaging;Dorsal;Exhibits;Funding;Goals;Human;human data;human subject;in vivo;Individual;Injections;insight;Insula of Reil;interest;Internal Capsule;Intervention;Label;Limb structure;Longitudinal Studies;Macaca;Maps;Measures;Methods;Modality;Morphologic artifacts;MRI Scans;neural circuit;neuroimaging;Noise;nonhuman primate;Pathway interactions;Patients;Positioning Attribute;Prefrontal Cortex;Protocols documentation;quality assurance;reconstruction;Resolution;Role;Scanning;Signal Transduction;Techniques;Therapeutic Intervention;tool;Tracer;tractography;Translating;Travel;white matter;Work

PROJECT_TITLE: Structural Connections Core


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Asthma;Clinical Research;Genetics;Health Effects of Indoor Air Pollution;Human Genome;Lung

ORG_CITY: LA JOLLA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Although the gene ORMDL3 is highly associated with the development of asthma, little is known about the function of ORMDL3 and how it may contribute to the development of asthma. In this study we will use immune cells cells from humans as well as a mouse model of asthma to determine how ORMDL3 causes asthma. This may provide insight into novel treatments for asthma.

PI_NAMEs: BROIDE, DAVID H (contact)

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: 17q21;airway remodeling;Alleles;Allergens;Allergic inflammation;Applications Grants;Asthma;asthma model;asthmatic;base editing;Biological;Biology;Blood Cells;Caring;CD4 Positive T Lymphocytes;Cell Adhesion;Cell Physiology;Cell Proliferation;Cells;Chemotaxis;Childhood;Chromosomes;cytokine;Development;ethnic diversity;Funding;Genes;genetic association;genome wide association study;House Dust;House Dust Mite Allergens;Human;Hypersensitivity;Immune;Immunology;In Vitro;in vivo;Individual;insight;knock-down;Laboratories;Link;Lung;Mediating;mouse model;Mus;Nature;novel;overexpression;Pathogenesis;Pathway interactions;Play;polarized cell;Population Heterogeneity;postnatal;postnatal period;Production;Proteomics;Pyroglyphidae;respiratory smooth muscle;response;risk variant;Role;Science;selective expression;Th2 Cells;trafficking;transcriptome sequencing;Transgenic Mice;Vascular Endothelial Cell

PROJECT_TITLE: Chromosome 17q21, allergic inflammation, and remodeling

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-T(57)]


NIH_SPENDING_CATS: Biotechnology;HIV/AIDS;Hematology;Infectious Diseases;Orphan Drug;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Project Narrative: Human Immunodeficiency Virus (HIV)-1 infection causes severe hematopathology; including anemia, neutropenia, thrombocytopenia, leukemia, lymphoma, inflammatory disorders, and bone marrow failure. A deeper understanding of the cellular and molecular mechanisms that regulate hematopoietic stem cells (HSCs) in the BM of patients with HIV-1 infection would be valuable in designing novel therapies for HIV-associated hematological diseases.

PI_NAMEs: RATHINAM, CHOZHA VENDAN (contact)

PROGRAM_OFFICER_NAME: SHANKAR, UDAY K

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Affect;Anemia;antiretroviral therapy;B-Lymphocytes;Biochemical;Biophysics;Bone Marrow;Bone marrow failure;Bone Marrow Neoplasms;bone marrow xenograft;Cell Culture Techniques;Cell Maintenance;Cell Physiology;Cells;Cellular biology;Common Lymphoid Progenitor;Consequences of HIV;Data;Defect;Dendritic Cells;design;Disease;effective therapy;Erythrocytes;Erythroid;Exhibits;Fluorescence;Frequencies;Genetic;granulocyte-monocyte progenitors;Hematological Disease;Hematology;Hematopathology;Hematopoiesis;Hematopoietic;hematopoietic differentiation;Hematopoietic Stem Cell subsets;Hematopoietic stem cells;HIV;HIV Infections;HIV therapy;HIV-1;HIV-1 load;Human;humanized mouse;IL3 Gene;Image;immunodeficiency;Impairment;In Vitro;in vivo;Infection;Inflammatory;insight;Investigation;Knowledge;leukemia;Link;Lymphoid;Lymphoma;Lymphopenia;Mediating;Megakaryocytes;Molecular;monocyte;mouse model;Multipotent Stem Cells;Mus;Myelogenous;Myeloid Progenitor Cells;Natural Killer Cells;Neutropenia;novel;novel therapeutics;Opportunistic Infections;Outcome;Pancytopenia;pathogenic virus;Patients;Persons;Physiological;Physiology;Predisposition;progenitor;Property;reconstitution;Research;Retrovirology;Reverse Transcriptase Polymerase Chain Reaction;self-renewal;Serum;Spectrum Analysis;stem cell biology;stem cell function;Techniques;Testing;Thrombocytopenia;Undifferentiated;Viral;Virus;Virus Diseases;whole genome;Xenograft procedure

PROJECT_TITLE: Decoding HIV-1 mediated Hematopathology

STUDY_SECTION: HCCS

STUDY_SECTION_NAME: HIV Comorbidities and Clinical Studies Study Section[HCCS]


NIH_SPENDING_CATS: Biomedical Imaging;Machine Learning and Artificial Intelligence;Mental Health;Neurosciences

PI_NAMEs: WANG, DANHONG  (contact)

PROJECT_TERMS: Address;advanced analytics;Anatomy;Area;association cortex;Award;Behavior;behavioral impairment;Cerebral cortex;Clinical;Computer Models;Corpus striatum structure;Data;Decision Making;denoising;Dictionary;experimental study;flexibility;Functional Magnetic Resonance Imaging;Funding;Goals;Grain;Human;Impairment;improved;Individual;innovation;Insula of Reil;inter-individual variation;Machine Learning;Maps;Measures;Meta-Analysis;Methods;Network-based;neural circuit;neural correlate;neuroimaging;Neurons;Noise;nonhuman primate;novel;Participant;Pattern;Positioning Attribute;Property;Protocols documentation;Publishing;response;Rest;Shapes;Signal Transduction;Techniques;Technology;Testing;Therapeutic Effect;Work

PROJECT_TITLE: Precision Functional Neuroimaging Core


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biotechnology;Charcot-Marie-Tooth Disease;Genetics;Lung;Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Peripheral Neuropathy;Rare Diseases;Spinal Muscular Atrophy

ORG_CITY: COLUMBIA

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

ORG_STATE: MO

PHR: Project Narrative - Relevance to Public Health Spinal Muscular Atrophy with Respiratory Distress Type I (SMARD1) is a devastating neurodegenerative disease with no effective treatment or cure. This project is designed to characterize two novel SMARD1 mice models that are based on patient mutations as well as evaluate some potential therapeutic targets. The characterization of these mice will provide a valuable resource towards understanding how IGHMBP2 mutants result in SMARD1 disease development.

PI_NAMEs: LORSON, CHRISTIAN L. (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Address;Adolescent;Affect;Age Months;Amyotrophic Lateral Sclerosis;ATP phosphohydrolase;autosome;Binding;Biochemical;Biochemical Pathway;Biochemistry;Biological;Biological Assay;Cell Physiology;cell type;Cessation of life;Charcot-Marie-Tooth Disease;Child;Chimera organism;Clinical;Communication;Complication;Cultured Cells;Data;Defect;Degenerative Disorder;design;Development;Disease;disease model;Distal;DNA;DNA Binding;early onset;effective therapy;Electrophysiology (science);Evaluation;experimental study;gene function;gene product;gene replacement;Genes;Genetic Transcription;Hand Strength;helicase;Heterozygote;Hindlimb;improved;knowledge base;Lead;Life Expectancy;life span;Lower Extremity;Missense Mutation;Modeling;Molecular;motor neuron degeneration;Motor Neuron Disease;Motor Neurons;mouse model;Mus;Muscle;Muscle Weakness;Muscular Atrophy;mutant;Mutant Strains Mice;Mutate;Mutation;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;neuromuscular;novel;Nucleic Acid Binding;nucleic acid binding protein;Onset of illness;Paralysed;Pathway interactions;patient population;Patients;Persons;Phenotype;Predisposition;Prevalence;protein B;protein expression;Proteins;Public Health;Ramp;Rare Diseases;Regulation;Research;residence;Resistance;Resources;respiratory;Respiratory distress;Respiratory Paralysis;Respiratory physiology;RNA;RNA Binding;RNA metabolism;Role;Series;Severity of illness;Spinal Muscular Atrophy;Spinal Muscular Atrophy with Respiratory Distress Type I;Symptoms;therapeutic development;therapeutic target;therapeutically effective;Time;tool;Transgenic Organisms;translational approach;Tyrosine-Specific tRNA;United States;Weight

PROJECT_TITLE: Novel SMARD1 Mouse Models: Characterization and Evaluation of Potential Therapeutic Targets

STUDY_SECTION: CDIN

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences

PI_NAMEs: FRANK, MICHAEL J. (contact)

PROJECT_TERMS: Anatomy;Automobile Driving;Behavior;Behavioral;Biological Markers;Brain;Classification;Clinical;clinical predictors;cognitive neuroscience;computer framework;Computer Models;Data;Decision Making;Diagnosis;Diagnostic;Diffusion;Diffusion Magnetic Resonance Imaging;Disease;Engineering;experience;Functional Magnetic Resonance Imaging;Goals;Graph;improved;improved outcome;Individual;interest;Intervention;Learning;Lesion;Link;machine learning classification;machine learning method;Maps;Measures;Methods;Modeling;Motivation;neural;neural circuit;neural correlate;neural network;neuromechanism;neuroregulation;neurotransmission;Outcome;Parameter Estimation;Pathway interactions;Patients;Pattern;predictive modeling;Probability;Process;Property;prospective;Psychiatry;Reaction Time;reduce symptoms;response;Rewards;Role;Sampling;Sensitivity and Specificity;Severities;Shapes;Site;symptomatology;Symptoms;System;Testing;Theoretical model;Validation;Variant

PROJECT_TITLE: Neurocomputational Modeling Core


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: ANN ARBOR

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Our preliminary findings show that RNA abasic sites are abundant, and they stabilize R-loops to regulate the transcription of noncoding RNA. To understand the scope of gene regulation by RNA abasic sites, we will identify their regulatory role genome-wide, identify the enzymes that form RNA abasic sites, and the bases that are removed to form the abasic sites.

PI_NAMEs: CHEUNG, VIVIAN G (contact)

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: Adenosine;Apolipoprotein E;base;Base Excision Repairs;Binding Proteins;cell type;Cells;Data;DNA;DNA Damage;DNA Polymerase II;DNA Repair;endonuclease;Endonuclease I;Enhancers;Enzymes;Gene Expression;Gene Expression Regulation;Genetic Transcription;genome-wide;hammerhead ribozyme;Hybrids;Length;Mass Spectrum Analysis;Mediating;Methylation;methylpurine;Modification;nucleic acid structure;Nucleic Acids;Pathway interactions;plant poison;prevent;Process;Proteins;Publishing;Reaction;Regulation;Research;response;Ribosomal RNA;Ricin;RNA;RNA Polymerase II;RNA Precursors;Role;Signal Transduction;Site;Stress;Structure;Untranslated RNA

PROJECT_TITLE: Determining the role of RNA abasic sites in gene regulation

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: WALTHAM

ORG_DEPT: BIOLOGY

ORG_NAME: BRANDEIS UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative Dynamic rearrangements of the actin cytoskeleton are essential for countless biological processes, including cell motility, endocytosis, cell division, intracellular transport, and cell and tissue morphogenesis. Furthermore, defects in actin regulation lead to a range of disorders, including Alzheimer’s disease, Huntington’s disease, Parkinson’s diseases, Amyotrophic Lateral Sclerosis (ALS), cardiovascular diseases, developmental disorders (e.g., limb deformities, infertility, and hearing impairment), and cancer. This proposal focuses on the molecular and cellular mechanisms underlying actin dynamics and organization. It takes aim at major gaps in our knowledge of how groups of actin regulatory proteins work together in multi-component mechanisms to govern actin dynamics in living systems. The proposed research will resolve these mechanisms, and in doing so provide new insights into the molecular basis of human disease.

PI_NAMEs: GOODE, BRUCE L (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Acceleration;Actins;Affect;Alzheimer's Disease;Amyotrophic Lateral Sclerosis;Animals;Binding;Biochemical;Biological;Biological Process;Cardiovascular Diseases;Cell division;cell motility;Cell Physiology;Cells;cellular imaging;cofilin;Complex;coronin protein;Cryoelectron Microscopy;Cytoskeleton;Cytosol;Defect;Deformity;depolymerization;developmental disease;Disease;Dissociation;Endocytosis;F-Actin;Filament;Funding;Genetic;genetic regulatory protein;Glia Maturation Factor;Goals;Growth;hearing impairment;human disease;Huntington Disease;In Vitro;in vivo;Individual;Infertility;inhibitor;insight;Intracellular Transport;Knowledge;Lead;Limb structure;Malignant Neoplasms;Mammalian Cell;Mediating;Microfilaments;Molecular;Morphogenesis;mutant;National Institute of General Medical Sciences;new technology;novel strategies;Nucleotides;Organism;Parkinson Disease;Process;protein structure;Proteins;reconstitution;Regulation;Research;Role;single molecule;Structure;System;Testing;Time;Tissues;Total Internal Reflection Fluorescent;Work;Yeasts

PROJECT_TITLE: Molecular and cellular mechanisms regulating actin dynamics

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


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Immunotherapy;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: IRVINE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE Regulatory T (Treg) cells play a central role in immune homeostasis and mitigating organ-specific autoimmune disorders including multiple sclerosis (MS), in which the immune system attacks axons in the Central Nervous System (CNS). Our goal is to investigate how Treg cells function to limit MS using two-photon microscopy to directly visualize cellular interactions in the CNS during experimental autoimmune encephalomyelitis (EAE), a murine model of MS. A better understanding of the cellular and molecular mechanisms of Treg cell function will aid in developing effective Treg-based therapeutic strategies to treat MS and several other autoimmune diseases.

PI_NAMEs: OTHY, SHIVASHANKAR  (contact)

PROGRAM_OFFICER_NAME: GUERAU, MIREIA

PROJECT_TERMS: Ablation;Antigen Presentation;Antigen-Presenting Cells;Antigens;Area;Autoimmune;Autoimmune Diseases;autoinflammatory;Axon;axon injury;base;Behavior;Benchmarking;Calcium;calcium indicator;Calcium Signaling;Candidate Disease Gene;cell behavior;Cell membrane;Cell Physiology;Cell Survival;Cell Therapy;Cells;Central Nervous System;Clinical Trials;Clonal Expansion;Clone Cells;CNS autoimmunity;Communicable Diseases;Complex;cost;Crowding;Cues;Detection;Development;Ensure;Environment;Evaluation;Experimental Autoimmune Encephalomyelitis;experimental study;Failure;fighting;follow-up;forkhead protein;Functional disorder;Genetic;Goals;healthcare burden;Home;Homeostasis;Image;Immune;immune imaging;Immune system;Immune System Diseases;immunological synapse;immunoregulation;Immunosuppression;in vivo;Infection;Inflammation;insight;Interleukin-2;Ion Channel;Knowledge;Label;lymphoid organ;Malignant Neoplasms;Mediating;Molecular;Monitor;Motility;mouse model;Movement;Multiple Sclerosis;Myelin;neuroinflammation;Organ;Organ Transplantation;Outcome;Pathologic;Pathway interactions;Pattern;Permeability;Phase;Physiological;Piezo 1 ion channel;Play;Positioning Attribute;preservation;Process;Proteins;ratiometric;Recovery;Regulatory T-Lymphocyte;remyelination;repaired;Reporter;Resolution;response;Role;Scanning;Signal Transduction;Spinal Cord;Surface;T-Cell Receptor;targeted treatment;Testing;Therapeutic;therapeutic evaluation;therapeutic target;tissue repair;Tissues;Transgenic Mice;two photon microscopy;two-photon;Visualization

PROJECT_TITLE: Tissue-Specific Mechanisms of Regulatory T Cells in the CNS during Autoimmune Encephalomyelitis

STUDY_SECTION: HAI

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


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Eye Disease and Disorders of Vision;Genetics;Machine Learning and Artificial Intelligence;Macular Degeneration;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE / PUBLIC HEALTH RELEVANCE Most common diseases afflicting human health result from complex combination of genetic, stochastic, behavioral and environmental factors interacting with age, whereas rare inherited retinal diseases (IRDs) are simpler single-gene defects that form the ideal basis for gene-based treatments. Despite decades of exciting progress, there is only one approved treatment for IRDs and a major contributing factor for this scarcity is the lack of biomarkers that can provide sensitive, reliable, and clinically meaningful measurement of photoreceptor degeneration over the duration of a typical clinical trial. This research plan is designed to fill this major gap for the most common molecular form of IRD which is Stargardt disease caused by ABCA4 mutations and forge a path to follow for other IRDs.

PI_NAMEs: CIDECIYAN, ARTUR V (contact)

PROGRAM_OFFICER_NAME: GAO, JAMES

PROJECT_TERMS: adaptive optics;Age;American;Anatomy;Apoptotic;Artificial Intelligence;artificial intelligence model;Atrophic;Attention;autosome;Behavioral;Biological Markers;Blindness;Cells;Clinical;Clinical Trials;cohort;Complex;Data;Data Set;design;Detection;Development;Dimensions;Disease;disease natural history;Disease Progression;efficacy evaluation;Environmental Risk Factor;Evaluable Disease;Evaluation;first-in-human;forging;Functional disorder;functional outcomes;Future;gene therapy;gene-targeted therapy;Genes;Genetic;Genomics;Health;Human;Image;improved;Individual;Inherited;inherited retinal degeneration;insight;Intervention;Intervention Trial;Learning;Literature;Location;longitudinal, prospective study;macula;Maps;Measurement;Measures;Methods;Molecular;Molecular Disease;Mutation;Neighborhoods;novel;Outcome Measure;Outcome Study;patient subsets;Patients;Peripheral;personalized predictions;Phenotype;Photophobia;photoreceptor degeneration;Photoreceptors;programs;prospective;public health relevance;Research;Retina;Retinal Cone;Retinal Diseases;retinal rods;Retinitis Pigmentosa;Risk;RPE65 protein;Single-Gene Defect;spatiotemporal;Stargardt's disease;Structure;successful intervention;Testing;therapy development;Thinness;Tissues;Training;Vertebrate Photoreceptors;Vision;Visit;visual dysfunction;Work;Wrestling

PROJECT_TITLE: Photoreceptor Disease in Inherited Retinal Degenerations

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 NV-P (81)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Infectious Diseases;Lung;Pediatric;Pneumonia;Pneumonia and Influenza

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Project Narrative Respiratory syncytial virus (RSV) infection can cause severe lung inflammation and life-threatening illness in young children but there are currently no available therapies to treat or prevent RSV. This study focuses on understanding how RSV infection triggers defective natural killer (NK) cell immunity and disrupts inflammation resolution pathways that contribute to lung inflammation and respiratory failure in children. Restoring host- protective NK cell immune pathways with specialized pro-resolving mediator molecules has the potential to lead to novel therapeutic approaches to accelerate the resolution of lung inflammation in RSV infection.

PI_NAMEs: DUVALL, MELODY G. (contact)

PROGRAM_OFFICER_NAME: NATARAJAN, ARUNA R

PROJECT_TERMS: 2 year old;Acceleration;Acute;Apoptosis;Biological Specimen Banks;Bronchiolitis;Cells;Cessation of life;Child;Childhood;Chronic;confocal imaging;Confocal Microscopy;cytokine;Cytoplasmic Granules;Cytoskeletal Proteins;Cytoskeleton;cytotoxicity;Data;Defect;effective therapy;endotracheal;Enrollment;Ensure;Equilibrium;Family;Fatty Acids;Flow Cytometry;Future;Health;Hospitalization;hospitalization rates;Hospitals;Host Defense;Human;Hypoxemia;Immune;Immune Targeting;Immunity;Immunologic Factors;immunological synapse;immunological synapse formation;Immunology;Immunophenotyping;immunoregulation;Impairment;Infant;Infection;Inflammation;Inflammatory;innovation;Intubation;Investigation;Knowledge;Laboratories;Leukocytes;Life;Link;lipoxin A4;Lytic;Mediating;Mediator;Motility;Mus;Natural Killer Cells;novel;novel therapeutic intervention;Outpatients;Pathway interactions;Patients;Pediatric Hospitals;Pediatric Intensive Care Units;Plasma;Pneumonia;post-pandemic;prevent;Prevention strategy;Process;Production;prospective;protein expression;Public Health;Pulmonary Inflammation;receptor;receptor expression;Recovery;recruit;Research;Resolution;Respiratory Failure;Respiratory syncytial virus;Respiratory Syncytial Virus Infections;Role;Severity of illness;Signal Pathway;Signal Transduction;Steroids;Supportive care;Techniques;Testing;Therapeutic;Time;Tissues;trafficking;ventilation;Viral;Virus;virus identification;Visit

PROJECT_TITLE: NK cell inflammation resolution circuits in pediatric RSV infection

STUDY_SECTION: LCMI

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


ORG_CITY: INDIANAPOLIS

ORG_DEPT: SURGERY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative Critical limb threating ischemia (CLTI), the most severe form of peripheral arterial disease, is characterized by rest pain and tissue loss, is a major risk factor for amputation, and accounts for over 10 billion dollars in medical costs annually. Surgical treatment for CLTI often is unsatisfactory or not a viable option, and there are no effective pharmacological therapies, especially for diabetic patients; thus, a great need exists for novel treatment strategies to stimulate vascularization, counteract ischemic muscle damage, and ultimately reduce the incidence of lower limb amputations. This proposal is designed to determine the potential of a novel vertebral bone adherent mesenchymal stromal cell, encapsulated in an alginate hydrogel, to ameliorate effects of CLTI and to determine mechanisms by which these cells promote muscle regeneration, ultimately leading to the development of molecular therapies for this major cardiovascular disease.

PI_NAMEs: MURPHY, MICHAEL PATRICK (contact)

PROGRAM_OFFICER_NAME: REID, DIANE M

PROJECT_TERMS: Address;Age;Alginates;Allogenic;Amputation;angiogenesis;Autologous;Biomimetics;Blood Vessels;Bone Marrow;Cardiovascular Diseases;cell preparation;Cell Therapy;Cells;Clinical Treatment;Clinical Trials;cohort;Conduct Clinical Trials;cytokine;Data;Death Rate;density;design;Development;diabetic;Diabetic mouse;diabetic patient;Diagnosis;diet-induced obesity;Disease;Dose;Encapsulated;exosome;experience;Future;gain of function;Genetic;Goals;Hindlimb;Histology;Human;Hydrogels;Immune;immune clearance;Immunohistochemistry;improved;Incidence;Inflammatory;Injections;Interleukin-10;Intervention;Investigational New Drug Application;Ischemia;Isolated limb perfusion;Lasers;limb amputation;limb ischemia;Limb structure;loss of function;Lower Extremity;Macrophage;Mediating;Medical Care Costs;mesenchymal stromal cell;Modeling;Modification;Molecular;Mononuclear;Morbidity - disease rate;Morphology;mortality;mouse model;Mus;Muscle;Muscle function;muscle regeneration;myogenesis;next generation;novel;Operative Surgical Procedures;Organ Donor;Pain;Pathway interactions;Patients;Perfusion;perfusion imaging;Peripheral arterial disease;pharmacologic;Phase;Phase I Clinical Trials;Phenotype;Population;Preparation;preservation;prevent;Production;Publishing;Refractory;regenerative therapy;Regulatory T-Lymphocyte;Rest;revascularization;Risk;Risk Factors;Role;Route;secondary analysis;Standardization;stem cell function;Suspensions;Testing;tissue regeneration;Tissues;treatment strategy;Vascularization;vertebra body;Vertebral Bone

PROJECT_TITLE: Human Vertebral Body Mesenchymal Stromal Cells from Organ Donors For  Limb Preservation in a Murine Model of Diabetic Hindlimb Ischemia

STUDY_SECTION: BTSS

STUDY_SECTION_NAME: Bioengineering, Technology and Surgical Sciences Study Section[BTSS]


ADMINISTERING_IC: DK

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Nutrition;Obesity;Pediatric;Physical Activity;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Umbilical Cord Blood/ Placenta;Stem Cell Research - Umbilical Cord Blood/ Placenta - Human;Women's Health Research

ORG_CITY: GREENVILLE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: EAST CAROLINA UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative Infants born to mothers with obesity during pregnancy are at greater risk of developing obesity. Lifestyle interventions, such as exercise, during pregnancy may be a viable strategy to offset this risk; however, mechanisms are lacking. This research project will be the first step to understanding the cellular mechanisms, using human umbilical-cord mesenchymal stem cells, of how maternal exercise decreases obesity risk in infants.

PI_NAMEs: BROSKEY, NICHOLAS  (contact)

PROGRAM_OFFICER_NAME: SILVA, CORINNE M

PROJECT_TERMS: 5 year old;5'-AMP-activated protein kinase;Adipocytes;Adult;Adverse effects;adverse outcome;Aerobic Exercise;Affect;Age;Age Months;American;Ancillary Study;Basal metabolic rate;Beta Cell;Bioenergetics;Blood;Body Composition;Body fat;Body mass index;Candidate Disease Gene;candidate identification;cell type;Cellular Metabolic Process;college;Data;Deposition;Discipline of obstetrics;Dual-Energy X-Ray Absorptiometry;Energy Metabolism;Enrollment;Epigenetic Process;Exercise;Exposure to;Fatty acid glycerol esters;fetal;Generations;Genes;Glucose;glycogen synthase kinase 3 beta;Gynecology;Health;Human;improved;indexing;Indirect Calorimetry;Infant;Infant Health;Insulin;insulin sensitivity;Life;lifestyle intervention;lipid biosynthesis;Lipids;longitudinal, prospective study;maternal obesity;Measures;Mesenchymal Stem Cells;Mesoderm Cell;Metabolic;metabolic profile;Metabolism;metabolomics;methylation pattern;Mitochondria;mode of exercise;Modeling;Mothers;multiple omics;Muscle Cells;myogenesis;Obesity;obesity in children;obesity in pregnancy;obesity risk;offspring;Outcome;oxidation;Oxidative Phosphorylation;parent grant;Parents;Pathway interactions;Phenotype;postnatal;Pregnancy;Pregnant Women;Production;Proteins;Publishing;Randomized;Recommendation;Research Personnel;Research Project Grants;resistance exercise;respiratory;Rest;Risk;Role;sedentary;stem cell model;Testing;Tissues;Translating;treatment as usual;Triglycerides;Umbilical cord structure;Weight;Woman;Work

PROJECT_TITLE: Effect of Maternal Exercise in Women with Obesity on Offspring Mesenchymal Stem Cell Metabolism

STUDY_SECTION: HSDO

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: MENANDS

ORG_NAME: WADSWORTH CENTER

PHR: PROJECT NARRATIVE The proposed research will develop working prototypes to enable imaging technology and provide previously unavailable polymer-based, indexing-patterned substrates and methods for correlative light and electron microscopy (CLEM) study of cells grown on porous substrates. These designable porous substrates will not only facilitate cells to obtain in vivo-like morphology and function but also simplify and streamline CLEM protocols, leading to better understanding of diseases at molecular and ultrastructral levels. Therefore, the proposed research is relevant to the part of the NIH’s mission that pertains to reducing illness and disability.

PI_NAMEs: SUI, HAIXIN  (contact);XIE, YUBING

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: 3-Dimensional;Address;Behavior;Biological;Biomedical Research;Cell Culture Techniques;Cell Enlargement;cell growth;cell type;Cells;cellular imaging;Cilia;Communities;density;Development;disability;Disease;Electron Microscopy;electron tomography;Electrons;Ensure;experience;fabrication;Feedback;Fluorescence Microscopy;Freeze Substitution;Freezing;functional status;Glass;Goals;Growth;Imaging technology;in vivo;indexing;innovation;interest;Ions;kinetosome;Label;light microscopy;live cell imaging;Location;Methods;Microfabrication;Microscopic;microscopic imaging;Mission;Molecular;Monitor;Morphology;Mus;Neon;novel;Organ;Organoids;Outcome;Pattern;Permeability;Plant Resins;Polymers;Porosity;Preparation;pressure;Production;Property;Protocols documentation;prototype;renal epithelium;Research;Resolution;Sampling;Scanning;Scientist;Specimen;Structure-Activity Relationship;System;Techniques;Technology;technology development;Testing;Thinness;three dimensional cell culture;Time;Tissues;tomography;tool;Training;Ultramicrotomy;United States National Institutes of Health;Validation

PROJECT_TITLE: Development of polymer-based cell culture substrates for correlative light and electron microscopy (CLEM)

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


NIH_SPENDING_CATS: Nutrition;Obesity;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: Contact PD/PI: Zhao, Shangang Project Narrative: Visceral adiposity is a major risk factor for development of metabolic disorders. Strategies that prevent visceral fat unhealthy expansion may be crucial to prevent and reverse metabolic disorders. The goal of this project is to uncover the paracrine effects of leptin in regulating visceral fat expansion. Project Narrative

PI_NAMEs: ZHAO, SHANGANG  (contact)

PROGRAM_OFFICER_NAME: BLONDEL, OLIVIER

PROJECT_TERMS: Acute;Adipocytes;Adipose tissue;Biochemical;Brown Fat;Cells;combat;CXCL14 gene;Dedications;Deterioration;Development;diet-induced obesity;Doxycycline;Fatty acid glycerol esters;Female;Gene Expression;glucose tolerance;Goals;Health;Heterogeneity;High Fat Diet;Histology;Hypertrophy;In Vitro;in vivo;Inflammation;insight;insulin sensitivity;Kidney;Leptin;Leptin deficiency;LoxP-flanked allele;male;Measures;Mediating;Mesentery;Metabolic;Metabolic Diseases;Metabolic syndrome;Modeling;mouse model;Mus;novel;Obesity;overexpression;paracrine;Physiological;Population;precursor cell;preservation;prevent;progenitor;promoter;Regulation;Regulatory Element;response;Risk Factors;Role;Signal Transduction;single cell sequencing;stem cells;Stromal Cells;subcutaneous;Tamoxifen;Techniques;Testing;Tissues;tool;transcriptome sequencing;Transgenic Mice;Visceral;Visceral fat

PROJECT_TITLE: Paracrine effects of leptin in regulating visceral fat expansion

STUDY_SECTION: BMDM

STUDY_SECTION_NAME: Basic Mechanisms of Diabetes and Metabolism Study Section[BMDM]


ORG_CITY: CLEVELAND

ORG_DEPT: GENETICS

ORG_NAME: CLEVELAND STATE UNIVERSITY

PHR: Project Narrative  Treatments are limited for infections of Trypanosoma brucei, which sequentially expresses different variant surface glycoproteins (VSGs, its major surface antigen) in a strictly monoallelic manner to evade the host’s immune response. We have found that RAP1 silences all but one VSG genes and suppresses VSG switching. In this proposal, we will investigate how RAP1’s novel nucleic acids binding activities and its interactions with other telomeric proteins, histones, and chromatin remodelers contribute to monoallelic VSG expression and proper antigenic variation.

PI_NAMEs: LI, BIBO  (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Affect;African Trypanosomiasis;Antigenic Variation;Binding;Cell Proliferation;Chromatin;Chromatin Remodeling Factor;Chromatin Structure;Chromosomes;Collaborations;Complex;Data;Development;Digestion;DNA;DNA Binding;ds-DNA;Electrophoretic Mobility Shift Assay;Ensure;Future;Gel;Gene Pool;Genes;genetic approach;Genetic Recombination;Genetic Transcription;Genome;genome integrity;Histones;Homologous Gene;Hong Kong;Human;Immune response;Immunologics;improved;In Vitro;in vivo;Infection;ISWI;Leishmania;Mediating;Membrane Glycoproteins;mutant;novel;Nucleic Acid Binding;Parasites;Parasitic infection;Pathogenesis;Play;Post-Translational Protein Processing;Proliferating;Property;Proteins;recruit;Regulation;Ribonucleases;RNA;RNA Binding;RNA Recognition Motif;RNA Sequences;Role;Signal Transduction;Site;Structure;Surface Antigens;telomere;Telomere Maintenance;Testing;Time;Titrations;Trypanosoma brucei brucei;Trypanosoma cruzi;Universities;Variant;Yeasts

PROJECT_TITLE: Essential functions of Trypanosoma brucei RAP1

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


NIH_SPENDING_CATS: Hematology;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project Narrative There are many possible ways for an infection in the lung to become a severe pneumonia. We will test whether a subset of pneumonias is severe because of a deleterious interaction between our coagulation system and our immune system within the infected lung. If so, this particular subset of pneumonia patients may respond favorably to therapies that interfere with these activities.

PI_NAMEs: MIZGERD, JOSEPH P (contact)

PROGRAM_OFFICER_NAME: MONGODIN, EMMANUEL FRANCK

PROJECT_TERMS: adverse outcome;Alveolar;Alveolar Macrophages;Anticoagulants;antimicrobial;Blood Cells;Blood Vessels;Cell Culture Techniques;Cells;Coagulation Process;differential expression;elastase inhibitor;Elastases;Epithelial Cells;Exhibits;extracellular;Feedback;Fibrin;Fibrinolysis;fibrogenesis;Gene Targeting;Genes;Genetic;Goals;Greater sac of peritoneum;Heterogeneity;Histopathology;Human;human subject;Hyperplasia;Immune system;improved outcome;Infection;Inflammatory;influenza pneumonia;inhibitor;Interruption;ITGAM gene;ITGB2 gene;Leukocyte Elastase;Leukocytes;Lung;lung injury;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;Necrosis;neutrophil;Oral cavity;Pathologic;Pathway interactions;Patients;pharmacologic;Phenotype;Plasmin;Pneumococcal Pneumonia;Pneumonia;pneumonia model;Pulmonary Inflammation;Pulmonology;recruit;Respiratory Tract Infections;Sorting;System;targeted treatment;Testing;Thrombin;Thromboplastin;Time;transcriptome;Vaccines

PROJECT_TITLE: Fibrin in the Infected Lung


NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: We have found that the gene TWIST1 increases the risk for multiple vascular diseases in humans, likely by causing smooth muscle cells in the blood vessel wall to multiply and change their cell properties, but the mechanisms by which this occurs are unclear. Our studies are designed to uncover how smooth muscle cells multiply and change their cell properties in very granular detail, and to determine how TWIST1 modifies this process to cause disease. We will also determine how common genetic changes in people with vascular disease affect TWIST1 expression and the risk for disease.

PI_NAMEs: WIRKA, ROBERT  (contact)

PROGRAM_OFFICER_NAME: SCHOPFER, DAVID WESLEY

PROJECT_TERMS: Ablation;Affect;Alleles;Antibodies;Apolipoprotein E;Architecture;Arterial Fatty Streak;Atherosclerosis;Bar Codes;Binding Sites;Biological Assay;Blood Vessels;causal variant;Cell Count;Cell Cycle;cell fate specification;Cell Lineage;Cell Proliferation;Cells;Cellular biology;Cleavage Under Targets and Release Using Nuclease;Clonal Expansion;Coronary Arteriosclerosis;Coronary artery;Data;design;Disease;disorder risk;DNA Binding;Enhancers;Felis catus;Fibroblasts;gene function;Gene Modified;Genes;Genetic;Genetic Transcription;Genetic Variation;genome wide association study;genome-wide;genomic locus;High Fat Diet;Human;Hyperplasia;In Situ;in vivo;Individual;inhibitor;knock-down;Knock-out;Lead;Lesion;Location;Luciferases;Maps;Mediating;migration;Modeling;Molecular;Molecular Target;mouse model;Moyamoya Disease;Mus;Mutation;novel;overexpression;Pathogenesis;Pathway Analysis;Pathway interactions;Peripheral arterial disease;Persons;Phenotype;Play;Process;Proliferating;Property;protective allele;Protocols documentation;Repression;Resources;Risk;risk variant;RNA;Role;Shapes;Signal Transduction;single-cell RNA sequencing;Smooth Muscle Myocytes;Stroke;transcription factor;Transcription Repressor;transcriptome sequencing;TWIST1 gene;Vascular Diseases

PROJECT_TITLE: The role of Twist1 in SMC phenotypic modulation during atherosclerosis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Biotechnology;Chronic Pain;Genetics;Human Genome;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy

ORG_CITY: RICHARDSON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

PHR: Project Narrative In individuals with neuropathic pain, females show increased expression of interferon gamma (IFNγ) induced genes in their dorsal root ganglia (hDRG) suggesting a potential sex specific mechanism in the production of pain. To elucidate which cells in hDRG are capable of releasing IFNγ, I will isolate each immune cell type from hDRGs of both sexes and perform transcriptomic and proteomic assessments looking for IFNγ genes and proteins. Then I will expose cultured hDRG neurons of both sexes to IFNγ and perform a comprehensive analysis looking at the functional, transcriptomic, and proteomic changes that occur to determine what alterations IFNγ could be causing at the hDRG to produce neuropathic pain.

PI_NAMEs: LESNAK, JOSEPH  (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Animal Model;Animals;Bioinformatics;Calcium;career;CD4 Positive T Lymphocytes;Cell Separation;cell type;Cells;cost;cytokine;cytotoxic;Data;Data Set;design;Development;experimental study;Exposure to;Female;Future;Generations;Genes;Genetic Transcription;Genomics;Goals;Healthcare;HIF1A gene;Human;human tissue;Hyperalgesia;Hypersensitivity;IFNGR1 gene;Image;Immune;immunoregulation;Individual;Inflammatory;insight;Institution;Interferon Type II;Learning;Ligands;Link;Macrophage;male;Measurement;Mediating;Molecular;monocyte;Neuroimmune;Neuroimmunomodulation;neuroinflammation;Neurons;next generation sequencing;Nociceptors;novel;novel therapeutics;Outcome;Pain;pain processing;pain reduction;painful neuropathy;phosphoproteomics;Physiological;Play;Postdoctoral Fellow;Prevalence;Production;Prostaglandins;Proteins;Proteomics;receptor;Reproducibility;Research;response;RNA;Role;secondary outcome;sex;Sex Differences;sexual dimorphism;Signal Transduction;single-cell RNA sequencing;Site;skills;Spinal Ganglia;T-Lymphocyte;Techniques;Technology;Testing;Therapeutic;Tissues;Training;transcription factor;transcriptome;transcriptome sequencing;transcriptomics;translational scientist;Viral;Virus Diseases;Wages;Work

PROJECT_TITLE: Elucidating the role of interferon gamma production and signaling in the generation of neuropathic pain in human dorsal root ganglia

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-4 Study Section [NST-4]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Complementary and Integrative Health;Infant Mortality;Mental Health;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention

PHR: PROJECT NARRATIVE This study will test the delivery of a tailored music intervention as an evidence-based therapeutic approach for very preterm infants hospitalized in the Neonatal Intensive Care Unit (NICU) during a critical period of brain development. We will test the effects of the intervention on acute and cumulative stress during the NICU stay, relevant measures of regional brain volumes (amygdala) and intranetwork connectivity (language and salience networks), and a range of neurodevelopmental outcomes, with a primary outcome of language performance at 2 years corrected age. The overall goal is to establish music medicine as an evidence-based innovative therapy in the neonatal intensive care unit that improve long-term neurodevelopmental outcomes for the ~63,000 very preterm infants born each year in the U.S. and many more worldwide.

PI_NAMEs: ERDEI, CARMINA  (contact);MONTGOMERY, ANGELA MARIE

PROGRAM_OFFICER_NAME: MILLER, BRETT

PROJECT_TERMS: 2 year old;Acoustics;Acute;acute stress;Adult;Age;aging brain;Amygdaloid structure;Area;arm;Auditory;Auditory area;Behavior;Behavioral;Biological Aging;Brain;Brain imaging;brain magnetic resonance imaging;Brain region;brain volume;capsule;Caring;Child;Child Behavior;Chronic stress;clinically relevant;Cognition;Cognitive;Communities;critical period;Data;deprivation;Development;Diffusion;Early Intervention;Electronics;Elements;Emotional;Employment;Environment;Evaluation;evidence base;experience;Exposure to;extreme prematurity;Family;Frequencies;Goals;Hospitalization;Human;Impairment;improved;Individual;Infant;innovation;Innovative Therapy;interest;Intervention;intervention effect;Intervention Studies;Investigation;Language;Language Delays;language outcome;Lead;Length;Long-Term Effects;Longterm Follow-up;Loudness;Magnetic Resonance Imaging;Measures;Medical;Medicine;Mental Health;Morbidity - disease rate;Music;Music Therapy;Neonatal Intensive Care Units;neurodevelopment;Neurodevelopmental Impairment;neuroimaging;neurosensory;Noise;novel;Observational Study;Outcome;Outcome Measure;Pain;Parents;Pathway interactions;Pattern;Performance;Perinatal;Periodicity;Physiological;postnatal;Pregnancy;premature;Premature Birth;Premature Infant;primary outcome;Primary Prevention;Radiation;Randomized;randomized trial;Randomized, Controlled Trials;Research Design;respiratory;Rest;Sample Size;School-Age Population;Schools;Sensory;skills;social;social communication;Societies;sound;Special Education;standard care;Stimulus;Stress;stress reduction;Structure;Survivors;Techniques;telomere;Testing;Therapeutic;Third Pregnancy Trimester;Time;Translating;Voice;white matter;Work;young adult

PROJECT_TITLE: The Impact of Music Medicine on Preterm Brain Development and Behavior

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-R (12)]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Arthritis;Genetics;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative: VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a newly identified inflammatory and hematologic disease caused by somatic mutations in UBA1. VEXAS syndrome is present in tens of thousands of Americans, confers higher morbidity and mortality, and remains treatment resistant. Here we propose to utilize mouse models to define the cellular and molecular mechanisms of disease to improve our understanding of pathogenesis and potential treatments.

PI_NAMEs: BECK, DAVID  (contact)

PROGRAM_OFFICER_NAME: PARK, HEIYOUNG

PROJECT_TERMS: Affect;American;Animal Model;autoinflammatory;Automobile Driving;B-Lymphocytes;Biochemistry;Blood;Bone Marrow;Cell Line;Cell model;cell type;Cells;Chemicals;Clinical;Clonal Expansion;conditional knockout;Cultured Cells;Cytoplasm;Disadvantaged;Disease;effective therapy;Enzyme Activation;Enzymes;Exhibits;experimental study;fitness;Goals;Hematological Disease;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Immune;improved;Individual;Inflammation;Inflammatory;inhibitor;insight;Knock-in;Lead;Link;LoxP-flanked allele;Lymphocyte;Lymphoid;Lymphoid Cell;Mediating;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;multicatalytic endopeptidase complex;Mus;mutant;Mutation;Myelogenous;Myeloid Cells;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Phenotype;Post-Translational Protein Processing;Process;progenitor;Protein Isoforms;Proteins;Proteomics;Refractory Disease;Regulation;Resistance;response;Rheumatism;Rheumatoid Arthritis;Role;Severity of illness;Signal Pathway;Signal Transduction;small molecule;Somatic Mutation;stem cells;Symptoms;Syndrome;systemic inflammatory response;T-Lymphocyte;Temporal Arteritis;Transgenic Mice;Transplantation;Ubiquitin;Vacuole;Work;Zebrafish

PROJECT_TITLE: Regulation of inflammation by the ubiquitin proteasome pathway

STUDY_SECTION: ACTS

STUDY_SECTION_NAME: Arthritis, Connective Tissue and Skin Study Section[ACTS]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Post-Traumatic Stress Disorder (PTSD);Social Determinants of Health;Substance Misuse

ORG_CITY: LITTLE ROCK

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: Project Narrative The cyclical nature and repercussions of the associations between addiction, incarceration, and traumatic stress have been thoroughly documented in decades of research. However, evidence-based, trauma-focused interventions are not often used in prisons, despite promising evidence that they may reduce drug use and crime by improving the mental health of incarcerated people prior to release. This study will: 1) test the effectiveness of a trauma-focused group therapy to reduce post-incarceration drug use; 2) evaluate implementation facilitation, a promising strategy for supporting uptake of the therapy in prisons, and 3) measure the cost of the therapy and the implementation strategy to inform later scale up.

PI_NAMEs: ZIELINSKI, MELISSA JEAN (contact)

PROGRAM_OFFICER_NAME: ZUR, JULIA BETH

PROJECT_TERMS: acceptability and feasibility;addiction;Adoption;Adult;Aftercare;Attention;Bibliotherapy;budget impact;Characteristics;Chronic;Clinical Treatment;Cognitive;cognitive testing;Communities;community burden;community living;Complex;Consolidated Framework for Implementation Research;Consultations;coping;cost;cost estimate;Cost Measures;Crime;Criminal Justice;Data;depressive symptoms;design;diagnostic criteria;drug abuse prevention;Drug Addiction;Drug usage;Drug Use Disorder;Drug user;Educational Status;Effectiveness;effectiveness outcome;effectiveness testing;effectiveness/implementation design;Enrollment;Ensure;evidence base;Evidence based intervention;Evidence based practice;experience;Exposure to;Female;flexibility;Focus Groups;Frequencies;Geography;Goals;Group Therapy;Guidelines;Hybrids;implementation evaluation;implementation facilitation;implementation outcomes;implementation strategy;Imprisonment;improved;Individual;International;Intervention;Interview;Justice;Link;Mediating;Mental Depression;Mental Health;Methods;Motion;National Institute of Drug Abuse;Nature;novel;novel strategies;Outcome;Participant;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Population;post intervention;Post-Traumatic Stress Disorders;post-traumatic symptoms;Prisons;Professional counselor;Protocols documentation;Provider;Randomized;randomized trial;recidivism;Records;reduced substance use;Relapse;Reporting;Research;Research Support;Risk;scale up;Schedule;secondary outcome;self help;Severities;Site;standard of care;Strategic Planning;Structure;Substance Use Disorder;Supervision;Surveys;Symptoms;System;Testing;Time;Training;Trauma;trauma exposure;traumatic stress;treatment as usual;treatment comparison;uptake;US State;Vision;Work

PROJECT_TITLE: Effectiveness, Implementation, and Cost of Cognitive Processing Therapy in Prisons

STUDY_SECTION: IPTA

STUDY_SECTION_NAME: Interventions to Prevent and Treat Addictions Study Section[IPTA]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: Project Relevance/Project Narrative Although a number of medicines have been used for the treatment of hypertension, more than 10 million of the patients are resistant to medications. The objective of this project is to develop a tissue-like bioadhesive electronic device that is soft, stretchable, and suture-free for the treatment of resistant-hypertension. Compared to existing devices for resistant-hypertension therapy, this novel device will significantly reduce the risk of tissue damage and inflammation, introduce minimal invasiveness to patients, providing the next-generation device for hypertension therapies and helping a huge number of resistant-hypertension patients control their blood pressure. 1

PI_NAMEs: ZHOU, TAO  (contact)

PROGRAM_OFFICER_NAME: LUNDBERG, MARTHA

PROJECT_TERMS: 3-Dimensional;3D Print;Acute;Adopted;Adverse effects;Animals;Baroreflex;bioelectronics;Blood Pressure;blood pressure reduction;carotid sinus;Charge;Chronic;design;Development;Device Designs;Devices;Drug resistance;Effectiveness;Electric Stimulation;Electrodes;Electronics;Ensure;Equipment Malfunction;experience;fabrication;Frequencies;Geometry;Goals;Healthcare Systems;Hydrogels;Hypertension;hypertension treatment;Implant;implantable device;improved;in vivo;Inflammation;Injections;manufacture;Measures;mechanical properties;Medical Device;Medicine;Metals;minimally invasive;Modeling;Modulus;Morbidity - disease rate;mortality;Nerve;Nervous System;neuroregulation;next generation;novel;Outcome;Patients;Periodicals;Pharmaceutical Preparations;Physiologic pulse;practical application;Property;Rattus;Research;resilience;Resistance;Resistant Hypertension;response;Risk Reduction;Safety;Stretching;success;Surgical sutures;System;Testing;therapy resistant;Time;Tissues;voltage;Width;Work

PROJECT_TITLE: 3D Printed Soft and Stretchable Tissue-Like Bioadhesive Electronic Device Enabled Neuromodulation for Resistant Hypertension Therapy


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

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Project Narrative  Dysregulation of gene expression is a frequent cause of disease. Expression of two genes is frequently coupled, for example in the case of bidirectional promoters which control the expression of about one in ten human genes, yet are poorly understood and we lack the technology to study them. We therefore propose to develop an integrated experimental and computational toolkit to study coupled expression of two genes.

PI_NAMEs: HANSEN, ANDERS SEJR (contact)

PROGRAM_OFFICER_NAME: DARINGER, NICHOLE MARIE

PROJECT_TERMS: Address;Architecture;Automobile Driving;Bacteriophages;Bayesian Analysis;Bayesian Modeling;Benchmarking;Binding Proteins;Biological Models;Biomedical Engineering;Bruck-de Lange syndrome;CCR5 gene;Cell Physiology;Cells;Collaborations;Communities;Computer Models;computerized tools;Computing Methodologies;Coupled;Data;Dedications;Detection;Disease;dosage;empowerment;Engineering;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Goals;Human;Human Characteristics;human imaging;Image;image processing;imaging modality;Label;live cell imaging;Location;machine learning method;mathematical model;Mathematics;Methodology;Methods;Microscope;Microscopy;Modality;Modeling;molecular imaging;Monitor;movie;Noise;open source;Photobleaching;Plasmids;promoter;Proteins;real-time images;Real-Time Systems;Regulation;Resolution;RNA;RNA Phages;Signal Transduction;single molecule;spatiotemporal;synthetic biology;System;Technology;Time;tool;Transcription Initiation Site;Visualization;Work

PROJECT_TITLE: An integrated toolkit for real-time analysis of coupled nascent transcription


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Androgen receptor signaling is a major player driving prostate cancer progression. This application is designed to elucidate the molecular mechanism by which loss of the chromatin remodeler gene CHD1 results in abnormal intratumoral androgen synthesis, aberrant activation of the androgen receptor, and resistance to antiandrogen therapy in prostate cancer. Studies in this propose will evaluate the anti-cancer efficacy of the newly identified small molecular inhibitors of the signaling pathway that drives antiandrogen therapy resistance in prostate cancer with loss of the CHD1 gene.

PI_NAMEs: DOMINGO-DOMENECH, JOSEP MARIA (contact);RODRIGUEZ-BRAVO, VERONICA

PROGRAM_OFFICER_NAME: VENKATACHALAM, SUNDARESAN

PROJECT_TERMS: abiraterone;Address;Adrenal Glands;advanced prostate cancer;Androgen Antagonists;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;Androgens;Anti-androgen Therapy;anti-cancer;Ants;Automobile Driving;Cancer Patient;cancer statistics;Castration;Cells;CHD1 gene;Cholesterol;Chromatin;clinically significant;CYP17A1 gene;Data;dehydroepiandrosterone;Dehydroepiandrosterone Sulfate;derepression;design;Disease;Down-Regulation;effective therapy;enzalutamide;Enzymes;Epigenetic Process;gene repression;Genes;Genetic;genetic corepressor;Genetic Transcription;genetic variant;Growth;Histone Acetylation;Histone H3;histone methylation;Hydroxysteroid Dehydrogenases;inhibitor;inhibitor therapy;intratumoral androgen;Knowledge;Link;loss of function;Lysine;Male Castration;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;Methylation;Molecular;next generation;novel;Output;Pathogenesis;Patients;Play;Post-Translational Protein Processing;preclinical efficacy;prostate cancer cell;prostate cancer progression;Proteins;Reader;Receptor Signaling;Resistance;Role;Sampling;Signal Pathway;Signal Transduction;Sin3A protein;small molecule inhibitor;Stanolone;Steroid biosynthesis;Steroids;Stress;Testing;Testosterone;therapeutic target;therapy resistant;Transactivation;transcription factor;Transcription Repressor;Up-Regulation

PROJECT_TITLE: Mechanism and therapeutic targeting of abnormal androgenesis in CHD1-deficient prostate cancer

STUDY_SECTION: MCTA

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics A Study Section[MCTA]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Childhood Obesity;Clinical Research;Genetics;Human Genome;Microbiome;Nutrition;Obesity;Pediatric;Precision Medicine;Prevention;Social Determinants of Health

ORG_CITY: CHAMPAIGN

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: PROJECT NARRATIVE The proposed research is relevant to improving human health because it will define how interactions between genetic and environmental factors in early life nutrition contribute to risk of childhood obesity. This project will leverage an on-going cohort to produce longitudinal genetic, microbiome, dietary, growth, and behavioral data sets for integration and development of predictive algorithms to identify at-risk children who would benefit from precision nutrition-guided interventions to prevent and treat childhood obesity.

PI_NAMEs: DONOVAN, SHARON MARIE (contact)

PROGRAM_OFFICER_NAME: MARUVADA, PADMA

PROJECT_TERMS: Adipose tissue;Affect;algorithm development;Bayesian Network;Behavior;Behavioral;biobank;Biological;Biological Markers;Birth;Body Composition;Child;Childhood;cognitive control;cohort;Computational Biology;contextual factors;Data;data integration;Data Set;Development;developmental plasticity;Diet;dietary;Dietary Component;Dietary intake;Dimensions;dopamine system;dysbiosis;early childhood;early-life nutrition;Eating;Eating Behavior;Emotional;Emotions;Environment;Environmental Risk Factor;Epigenetic Process;epigenome;epigenome-wide association studies;evidence based guidelines;executive function;Exhibits;fecal microbiota;Firmicutes;Genes;Genetic;Genetic Risk;Genetic Variation;Genome;genome wide association study;Growth;gut microbiome;Health;Human;improved;indexing;Individual;infancy;Inflammation;Informal Social Control;Intervention;Knowledge;Life;Link;Maps;Measures;Mediating;Methylation;microbial;microbial community;microbiome;microbiome composition;microbiota composition;Modeling;network models;neural network;novel;novel strategies;nutrition;Obesity;obesity development;obesity in children;obesity risk;Outcome;Pathway Analysis;Pathway interactions;personalized predictions;Phenotype;Phylogenetic Analysis;precision nutrition;predicting response;prediction algorithm;Predisposition;prevent;Process;Psychosocial Factor;Questionnaires;rapid growth;rapid weight gain;Regulation;Research;Risk;Risk Factors;risk variant;Sampling;Serotonergic System;Serotonin;serotonin transporter;System;Systems Biology;Temperament;Testing;theories;Time;Training;Tryptophan Metabolism Pathway;Variant;Weight;Weight Gain

PROJECT_TITLE: Elucidating Gene-Environment-Behavior Interactions to Uncover Causal Mechanisms for Obesity in Early Life


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: Project Narrative This project will equip neuroscience researchers, radiologists, MRI technologists, and study coordinators with au- tomatic, objective, fast, and accurate tools for image quality assessment so that timely decisions for re-scans can be made to improve the likelihood of collecting usable structural MRI data of sufficient sample size for subsequent analyses. Our tools will allow (i) high-speed image quality assessment with high specificity and sensitivity, (ii) ret- rospective artifact correction without the need for modification of pulse sequences or mounting of motion markers, and (iii) method generalizability and optimality for multiple sites, scanners, and imaging protocols without explicit data sharing. Successful completion of this project will allow image quality assurance to be done automatically in large-scale, multi-site, and longitudinal studies, and increase the amount of usable data for improving statistical power.

PI_NAMEs: YAP, PEW-THIAN  (contact)

PROGRAM_OFFICER_NAME: DUAN, QI

PROJECT_TERMS: Agreement;Algorithms;Artificial Intelligence;Brain;Collaborations;computerized tools;Consumption;Data;data acquisition;data curation;Data Set;data sharing;deep learning;design;Ensure;Ethics;Excision;Eye;Goals;Head;hemodynamics;Human;human imaging;Image;image processing;Imaging Device;imaging facilities;improved;Individual;Institution;Intelligence;Intervention;large datasets;Legal;Longitudinal Studies;magnetic field;Magnetic Resonance Imaging;Manuals;Medical;Methods;millisecond;Modification;Morphologic artifacts;Motion;neural network;Neurosciences;novel;Patients;Performance;Physiologic pulse;Predisposition;Protocols documentation;quality assurance;Quality Control;radiologist;Research Personnel;Sample Size;Sampling;Scanning;Sensitivity and Specificity;Site;Slice;Speed;Structure;supervised learning;Surface;Techniques;Time;tool;Training;trend;unsupervised learning;usability;Visual

PROJECT_TITLE: AI-Powered MRI Quality Control and Artifact Correction for Multi-Site Studies

STUDY_SECTION: EITN

STUDY_SECTION_NAME: Emerging Imaging Technologies in Neuroscience Study Section[EITN]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE  Degeneration of the inner ear hair cells is the major cause for hearing loss. De novo regeneration of the hair cells presents promising approaches to treat hearing loss. The proposed studies are aiming at identifying genes and genetic processes essential for the early development of mammalian cochlea and the formation of the organ of Corti and will provide the foundation for future treatment for hearing loss.

PI_NAMEs: GAN, LIN  (contact)

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Abate;Acceleration;Affect;Afferent Neurons;ATAC-seq;Binding;Biological Process;Candidate Disease Gene;candidate identification;CDKN1B gene;cell type;Cochlea;cochlear development;Cochlear duct;Code;combinatorial;Compensation;competence factor;Complex;conditional knockout;Cyclin-Dependent Kinase Inhibitor;Development;Ectopic Expression;Epithelial Cells;Epithelium;Event;experimental study;Failure;Foundations;Future;GATA3 gene;gene regulatory network;Genes;Genetic;Genetic Processes;Genetic Transcription;hair cell regeneration;Hair Cells;hair regeneration;hearing impairment;hearing loss treatment;hearing restoration;homeodomain;Impairment;Inner Hair Cells;islet;Knock-out;Knowledge;Laboratories;Labyrinth;LIM Domain;Modeling;Molecular;mutant;Natural regeneration;Neurons;novel;null mutation;Organ;Organ of Corti;Outcome Study;Outer Hair Cells;Pathogenesis;Pathway interactions;Pattern;Play;Proteins;Regenerative Medicine;Regulation;Role;Sensorineural Hearing Loss;Sensory;single nucleus RNA-sequencing;Specific qualifier value;spiral ganglion;Supporting Cell;Technology;Testing;Tissues;transcription factor;transcriptome sequencing

PROJECT_TITLE: Genetic Regulation of Cochlear Duct Patterning and Prosensory Formation

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Cerebral Palsy;Clinical Research;Neurosciences;Patient Safety;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Physical Rehabilitation;Rehabilitation

ORG_CITY: SALT LAKE CITY

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE The proposed research is relevant to public health with the goal to improve orthopaedic management of foot deformity for individuals with cerebral palsy by evaluating hindfoot function using biplane fluoroscopy and establishing standardized bone coordinate systems for consistent and accurate measurement of kinematics. Our contribution here is expected to include a robust approach for defining accurate standardized bone coordinate systems that are agnostic to asymptomatic, pathological, and deformity morphometric variation. This study is expected to identify long-term surgical correction strengths and deficiencies in adult patients living with CP and to provide knowledge to guide future clinical decision-making to improve long-term surgical interventions that benefit these patients as they grow into adulthood and achieve independence.

PI_NAMEs: LENZ, AMY L. (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Activities of Daily Living;Address;Adult;Advisory Committees;Affect;Age;Ankle;Articulation;Automobile Driving;Bilateral;Biomechanics;bone;Cerebral Palsy;Chicago;Childhood;Clinical;clinical decision-making;Clinical Research;Collaborations;comparison control;Data;Data Collection;Deformity;Diagnosis;disability;Effectiveness;Engineering;Ensure;Evaluation;Fluoroscopy;foot;Foot Deformities;Future;Gait;Goals;Growth;Human;improved;in vivo;Individual;insight;International;Intervention;Investigation;Joints;kinematics;Knowledge;Lateral;lateral column;Long-Term Effects;Longitudinal Studies;Longterm Follow-up;Measurement;Measures;Methods;Mission;model development;Modeling;Morphology;Motion;Neurologic;novel;Operative Surgical Procedures;Orthopedics;Orthotic Devices;Osteotomy;Outcome;Pain;Pain Free;Palpable;Paper;Pathologic;Patients;Pediatric Hospitals;pediatric patients;Phase;Population;prevent;Protocols documentation;Puberty;Public Health;Publishing;Quality of Care;Quality of life;Recommendation;reconstruction;recruit;Reporting;Research;research study;Site;Societies;standard measure;Standardization;Subtalar joint structure;success;Surface;Surgeon;surgery outcome;System;Talus;Time;transition to adulthood;Universities;Utah;Variant;Weight Gain;Work

PROJECT_TITLE: Post-Surgical Form and Function of Planovalgus Foot Deformities in Patients with Cerebral Palsy

STUDY_SECTION: MRS

STUDY_SECTION_NAME: Musculoskeletal Rehabilitation Sciences Study Section[MRS]


NIH_SPENDING_CATS: Biotechnology;Infectious Diseases

ORG_CITY: MADISON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Fungi, including the spore-forming environmental yeast Cryptococcus, are emerging pathogens that cause life- threatening diseases in humans. The proposed research is relevant to public health because determining the fundamental biology of Cryptococcus spores and how they infect the mammalian lung will provide information necessary to understand how fungal pathogens infect people and cause fatal diseases. This project is relevant to the missions of the NIH and NIAID because it proposes basic research that will ultimately lead to new strategies to prevent and/or treat severe fungal disease, which will enhance human health and reduce illness, particularly among immunocompromised patients.

PI_NAMEs: HULL, CHRISTINA M (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Affect;Alveolar Macrophages;anti-fungal agents;Basic Science;Biochemical;Biogenesis;Biological;Biological Assay;Biological Models;Biology;Blood Circulation;Case Fatality Rates;Cell Culture Techniques;cell type;Cells;cellular targeting;Central Nervous System;Cessation of life;chemical genetics;Chemicals;chemotherapy;Competence;Cryptococcosis;Cryptococcus;Dangerousness;Death Rate;Development;Disease;Disease Progression;emerging pathogen;Environment;Equus caballus;Event;experience;experimental study;Fungal Spores;fungus;Gene Expression Profiling;Genetic;Germination;Goals;Growth;Growth and Development function;Health;high risk;high throughput screening;Human;Immunocompromised Host;improved;In Vitro;in vivo;Individual;Infection;Infiltration;Inhalation;innovation;insight;Invaded;Investigation;Kinetics;Laboratory Study;Life;Lung;Maps;Mediating;Meningoencephalitis;Mission;Modeling;Molecular;Molecular Genetics;Molecular Target;Morbidity - disease rate;mortality;mouse model;Mus;National Institute of Allergy and Infectious Disease;novel;novel therapeutic intervention;novel therapeutics;particle;pathogen;Pathogenesis;pathogenic fungus;Pathogenicity;Pathway interactions;Patients;Persons;Phagocytes;Phagocytosis;Population;population based;prevent;Prevention;Prevention strategy;Process;programs;Proteins;Proteomics;Public Health;Reaction;Reporting;Repression;Reproduction spores;Research;Resolution;Role;skills;Study models;System;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;Time;tissue culture;Tissues;tool;Toxic effect;Transcript;transcriptome;transcriptomics;Transplant Recipients;United States;United States National Institutes of Health;virtual;Work;Yeasts

PROJECT_TITLE: Maturation, Germination, and Pathogenesis of Cryptococcus Spores


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

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: NARRATIVE We discovered a new posttranslational modification of TDP-43, citrullination (citR), and confirmed its accumulation in Limbic-Predominant Age-related TDP-43 Encephalopathy (LATE) human brain and TDP-43 animal models. We state that the "coordinated activation state” of peptidyl arginine deiminase 4 (PAD4) induces citrullination of TDP-43, impairs protein function, promotes cytoplasmic accumulation and aberrant protein phase-separation dynamics. This application will unravel mechanisms of PAD4-mediated citrullination implicated in TDP-43 pathogenesis that characterize LATE and ADRDs.

PI_NAMEs: SELENICA, MAJ-LINDA B (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: Acceleration;Affect;aging population;Alzheimer's disease related dementia;Animal Model;Antibodies;Arginine;Arginine deiminase;Biochemical;Biological Markers;Biology;Brain;Brain region;Cells;Chronic;Citrulline;Clinical;Cognitive deficits;comorbidity;Custom;Cytoplasm;Data;Dementia;digital;DNA-Binding Proteins;Epitopes;Fostering;Functional disorder;gain of function;Genes;Genetic;Human;human tissue;Impaired cognition;Impairment;In Vitro;in vivo;indexing;Kinetics;Laboratories;limbic-predominant age-related TDP-43 encephalopathy;Liquid substance;loss of function;Mass Spectrum Analysis;Mediating;mimetics;mouse model;neurobehavioral;Neurons;Neuropathogenesis;neuropathology;novel;Nuclear Import;nucleocytoplasmic transport;Outcome;Pathogenesis;Pathologic;Pathology;Phase;Phase Transition;Phenotype;Phosphorylation;Post-Translational Protein Processing;protein aggregation;protein function;protein TDP-43;Proteins;Public Health;Recombinants;response;Risk;Role;Solid;Solubility;Spectrum Analysis;Synapses;TDP-43 aggregation;Testing;Work

PROJECT_TITLE: Emerging role of PAD4 mediated TDP-43 citrullination in the neuropathology of LATE and Alzheimer’s Disease Related Dementias

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 AN-Q (55)]


NIH_SPENDING_CATS: Brain Disorders;Cerebrovascular;Congenital Structural Anomalies;Neurosciences;Pediatric;Stroke

ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: Project Narrative Although brain arteriovenous malformations (bAVMs) are a high-risk factor for intracerebral hemorrhage, especially for young patients, the pathophysiology is not well understood, and the treatment options are severely limited. By the notion that endothelial-to-mesenchymal transition (EndMT) is involved in human bAVM, the current proposal addresses the underlying molecular mechanisms of the EndMT in bAVM development by in vivo and in vitro approaches using our novel mouse model of bAVM. The proposal is relevant to the NIH's mission because understanding the pathomechanisms of bAVMs could lead to the development of therapeutic strategies for bAVM patients, subsequently preventing hemorrhagic stroke and improving their life quality.

PI_NAMEs: KIM, EUNHEE  (contact)

PROGRAM_OFFICER_NAME: KOENIG, JAMES I

PROJECT_TERMS: Address;Animal Model;Arteries;Arteriovenous malformation;Astrocytes;Attenuated;Blood Vessels;Brain;brain arteriovenous malformations;brain endothelial cell;Brain hemorrhage;cadherin 5;Calpain;calpain inhibitor;Cardiac;Caspase;CD44 gene;Cell Physiology;Cells;Cerebral hemisphere hemorrhage;Cessation of life;Characteristics;Clinical Research;clinically relevant;Coculture Techniques;comparison control;Data;Development;disability;Electrical Resistance;Endothelial Cells;Endothelium;Family;Functional disorder;Gene Expression;Genes;Goals;Hemorrhage;high risk;Human;improved;In Vitro;in vivo;Incidence;Induced Mutation;inhibitor;Injections;Intervention;ITPR1 gene;KRAS2 gene;KRASG12D;Life;Lung;MADH4 gene;Matrix Metalloproteinases;Measures;Mediating;Mediator;MEKs;Mesenchymal;Methods;Mission;Molecular;mouse model;Mus;mutant;Mutate;Mutation;N-Cadherin;Neurofibrillary Tangles;Neurologic Deficit;notch protein;novel;Operative Surgical Procedures;overexpression;Pathology;Pathway interactions;Patients;Pharmacological Treatment;Phenotype;prevent;Process;Proliferating;Protein Isoforms;Proteins;prototype;Quality of life;Reporting;Research;Resected;Risk Factors;Role;Signal Transduction;single-cell RNA sequencing;slug;STAT3 gene;System;Testing;Tetanus Helper Peptide;therapeutic development;Time;Transforming Growth Factor beta;treatment strategy;Tube;United States National Institutes of Health;Veins;VWF gene

PROJECT_TITLE: Endothelial-to-mesenchymal transition in mutant KRAS-induced brain as a cause of arteriovenous malformations

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Cardiovascular;Clinical Research;Genetics;Heart Disease;Human Genome;Pediatric;Precision Medicine;Prevention

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

PHR: PROJECT NARRATIVE Thoracic aortic aneurysm is a prevalent and currently incurable cardiovascular disease associated with significant morbidity and mortality, which affects children and adults. The proposed research seeks to identify novel genetic factors that modify its degree of severity and to develop a novel echocardiographic image analysis algorithm. We anticipate that the knowledge arising from this research will benefit patients by increasing the ability to give more precise assessment of prognosis and tailor management accordingly as well as identify mechanisms that may be amenable to future therapeutic targeting.

PI_NAMEs: LANDIS, BENJAMIN JOHN (contact)

PROGRAM_OFFICER_NAME: CHARETTE, MARC F

PROJECT_TERMS: 3' Untranslated Regions;Adopted;Adult;Affect;Age;Algorithmic Analysis;Algorithms;Alleles;Aorta;automated algorithm;automated analysis;bicuspid aortic valve;biobank;Biological Assay;Biomedical Engineering;Blood specimen;Cardiac;Cardiology;Cardiovascular Diseases;Caring;Child;Child health care;Childhood;Classification;Clinical;Clinical Data;clinical imaging;Clinical Research;cohort;Collaborations;Data;Data Collection;data integration;Data Set;Decision Making;Development;Diagnosis;Diameter;Disease Progression;disorder risk;Dissection;DNA;Echocardiography;Enhancers;Enrollment;Etiology;Evaluation;follow-up;Freezing;Future;gene regulatory network;Genes;Genetic;Genetic Markers;Genetic Transcription;genetic variant;genome sequencing;Goals;Health;heart imaging;Heritability;Hospitals;Human;Image;Image Analysis;image archival system;improved;Indiana;inter-individual variation;Investigation;kinematics;Knowledge;Lead;longitudinal analysis;Measurement;medical schools;Methods;Modeling;Molecular;Molecular Analysis;molecular imaging;Monitor;Morbidity - disease rate;Morphology;mortality;Nervous System Disorder;next generation sequencing;novel;Operative Surgical Procedures;Outcome;Participant;Pathogenesis;Patients;personalized care;Phenotype;Population;precision medicine;predict clinical outcome;prevent;Prognosis;programs;Property;Regulator Genes;Reporter;Research;Resources;Risk;risk prediction;Sample Size;Sampling;Severities;Single Nucleotide Polymorphism;Smooth Muscle Myocytes;Subgroup;Testing;therapeutic target;Thoracic aorta;Thoracic Aortic Aneurysm;Time;Tissue Sample;Tissues;tool;transcriptome sequencing;transcriptomics;Universities;Untranslated RNA;whole genome

PROJECT_TITLE: Novel molecular and cardiac imaging paradigms for precision medicine in aortopathy

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


ORG_CITY: Aurora

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Narrative Recent experiments reveal that the scaffold and neurotransmitter receptor proteins that make up synapses are not homogeneously distributed as previously thought, but cluster into one or more distinct nanometer- scale structures within the synapse. The functional significance of these structures remains unclear. To investigate their role in synaptic function, we propose to apply novel tools we previously developed to rapidly and reversibly control their size and position within the synapse. Understanding how these structures influence synapse function will deepen our understanding of how they contribute to neural signaling in the healthy brain and whether they play a role in synaptic dysfunction responsible for numerous brain diseases and disorders.

PI_NAMEs: KENNEDY, MATTHEW J (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: Acute;Address;Affinity;affinity labeling;antibody engineering;Binding Sites;Brain;Brain Diseases;Calibration;Coupled;Data;density;Elements;Excitatory Synapse;experimental study;Functional disorder;Glutamate Receptor;Glutamates;Inhibitory Synapse;Link;Measurement;Measures;Modeling;N-Methyl-D-Aspartate Receptors;nano;nanoarchitecture;nanocolumn;nanometer;nanoscale;Nanostructures;neurotransmission;Neurotransmitter Receptor;neurotransmitter release;Neurotransmitters;novel;novel strategies;Optics;optogenetics;Plant Photoreceptors;polypeptide;Positioning Attribute;postsynaptic;Postsynaptic Membrane;presynaptic;Probability;Property;Reagent;receptor;Receptor Activation;receptor binding;recruit;Regulation;response;Role;scaffold;sensor;Series;Site;Structure;Study models;Synapses;synaptic function;Synaptic Receptors;Synaptic Transmission;Testing;Time;time use;tool;Variant;vesicular release;Work

PROJECT_TITLE: Evaluating the functional impact of synaptic nanoarchitecture

STUDY_SECTION: NC

STUDY_SECTION_NAME: Neuronal Communications Study Section[NC]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Emerging Infectious Diseases;Genetic Testing;Genetics;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: Newark

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Summary This project will develop a new way to easily test for many genetic mutations in a single test using a simple device that could be used at the point of care. When applied to tuberculosis, most types of drug resistance will be easily and rapidly diagnosed. This innovative diagnostic could vastly simplify treatment decisions and potentially save hundreds of thousands of lives.

PI_NAMEs: ALLAND, DAVID  (contact)

PROGRAM_OFFICER_NAME: LACOURCIERE, KAREN A

PROJECT_TERMS: Address;analytical method;Biological Assay;Blinking;Catalogs;causal variant;Chemistry;Clinical;clinically relevant;Collaborations;Companions;design;Detection;detection limit;detection platform;Development;Devices;Diagnostic;diagnostic development;Diagnostic tests;digital;Disease;DNA Sequence Alteration;Drug resistance;Drug resistance in tuberculosis;Drug resistant Mycobacteria Tuberculosis;Engineering;Ethambutol;fluoroquinolone resistance;Fluoroquinolones;Foundations;Future;Genes;innovation;instrument;Intermediate resistance;isoniazid;Laboratories;Length;Linezolid;low and middle-income countries;Mechanics;melting;Molecular;molecular diagnostics;mutant;Mutation;Mutation Detection;Mycobacterium tuberculosis;nano;novel;novel diagnostics;novel therapeutics;Nucleic Acid Amplification Techniques;Nucleic Acids;Performance;Pharmaceutical Preparations;point of care;point of care testing;Predisposition;Process;promoter;Pyrazinamide;Pyrazinamide resistance;rapid diagnosis;Rapid diagnostics;Resistance;resistance gene;resistance mutation;Resources;Rifampin;Risk;Sampling;Scientist;Specificity;Specimen;Sputum;System;Technology;Temperature;Testing;Time;Tuberculosis;tuberculosis diagnostics;tuberculosis drugs;tuberculosis treatment;United States National Institutes of Health;validation studies;Vertebral column

PROJECT_TITLE: Nanoreactor beads for POC TB resistance testing

STUDY_SECTION: EDIT

STUDY_SECTION_NAME: Etiology, Diagnostic, Intervention and Treatment of Infectious Diseases Study Section[EDIT]


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: The goal of this project is to establish novel modRNA formulations that tailor expression of proteins to specific cell types and determine how expression in specific cells directs immunity to modRNA-encoded protein.

PI_NAMEs: BROWN, BRIAN D (contact)

PROGRAM_OFFICER_NAME: SPAIN, LISA M

PROJECT_TERMS: 2019-nCoV;3' Untranslated Regions;adaptive immunity;Affect;Animals;Antibodies;Antibody Response;Antigen Presentation;Antigen-Presenting Cells;antigen-specific T cells;Antigens;B-Lymphocytes;Biodistribution;cell type;Cells;Data;Drug Delivery Systems;Drug Formulations;Drug usage;Endothelium;enzyme replacement therapy;expression vector;FDA approved;Genetic Transcription;Goals;Hematopoietic;Hepatocyte;Human;immune activation;Immune response;Immunity;Immunization;Immunophenotyping;In Vitro;in vivo Model;Injections;lipid nanoparticle;Medicine;Messenger RNA;MicroRNAs;Modeling;Muscle Cells;Neurons;novel;Nucleosides;Organ;Outcome;Pattern;Pharmaceutical Preparations;Phenotype;Population;prevent;protein expression;Proteins;Publishing;Reporter;Reporting;RNA;RNA vaccine;Site;Specificity;stem cells;T-Lymphocyte;Technology;Testing;Therapeutic;therapeutic protein;transcriptomics;Transfection;transgene expression;Transgenes;vaccine efficacy;vector;Work

PROJECT_TITLE: microRNA-controlled mRNA therapeutics

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-X (81)]