ORG_CITY: HADLEY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

PHR: Project Narrative This project will explore the role of daily rhythms on tissue regrowth for the first time by incorporating rhythms in lab studies, reinstating lost rhythms, and ensuring we give therapeutics at the correct time of day. We will develop robotic and drug delivery tools to control these rhythms and to align therapeutics with them. This work can unlock unexplored mechanisms that can help us improve tissue growth for lab studies and tissue regeneration in patients.

PI_NAMEs: KEARNEY, CATHAL J (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Affect;biological systems;bone;Cell Culture Techniques;Cells;circadian;Circadian Dysregulation;Circadian Rhythms;Clinic;Culture Setup;Diabetes Mellitus;Disease;Drug Delivery Systems;Ensure;falls;Foundations;Future;Glucocorticoids;Growth;Growth Factor;improved;In Vitro;in vivo;Individual;Lead;Light;Natural regeneration;Obesity;patient population;Patients;Periodicity;Pharmaceutical Preparations;Phase;Play;Probability;Process;product development;repaired;Research;robotic device;Robotics;Role;Signal Transduction;Site;Skin;System;Temperature;Testing;Therapeutic;Therapeutic Uses;Time;tissue culture;Tissue Engineering;tissue regeneration;tissue repair;Tissues;tool;tool development;Translating;ultrasound;Vascularization;Vision;Work

PROJECT_TITLE: It Will All Get Better with Time: Circadian Rhythms in Tissue Engineering


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: Aurora

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOCHEMISTRY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: NARRATIVE Many enzyme families use NADP(H) and NAD(H) as coenzymes for their catalytic function, whereby they utilize a hydride (the H-) for oxidation or reduction as defined within the giant family of oxidoreductases. We have discovered that the single hydride controls a global change within the Biliverdin Reductase B (BLVRB) family, which are essential redox regulators in multiple organisms. The novelty here is that despite the ubiquitous nature of NADP(H) and NAD(H)-dependent enzymes, this will be the first study aimed at elucidating the atomic resolution mechanism of global regulation mediated by the hydride in a family of reductases.

PI_NAMEs: EISENMESSER, ELAN Z (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TITLE: The global regulation of dynamics and structure mediated by single hydride in a family of reductases

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: LOS ANGELES

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: PROJECT NARRATIVE This proposal will provide fundamental new knowledge on the mechanisms and rules for exporting mitochondrial DNA-encoded double-stranded RNAs into the cytosol of mammalian cells. This process and pathway becomes activated during times of mitochondrial stress and induces a robust immune response, thereby resembling an infection by a double-stranded RNA virus coming from outside of a cell. Mutations in the central component of this process and pathway, PNPase (polynucleotide phosphorylase), have been identified in inherited deafness and in neurodegenerative diseases, highlighting the importance of this export pathway in human health and disease.

PI_NAMEs: KOEHLER, CARLA M (contact);TEITELL, MICHAEL A

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Alcoholic Liver Diseases;Alleles;Area;Autoimmune Diseases;Base Pairing;BAX gene;Binding;Biogenesis;biological adaptation to stress;Biological Markers;Biological Models;Biology;Categories;Cells;Code;cohort;Critiques;Cytosol;Data;deafness;Defect;Development;Disease;DNA;Double Stranded RNA Virus;Double-Stranded RNA;Embryo;Enterobacteria phage P1 Cre recombinase;Enzymes;Equipment;Exoribonucleases;exosome;extracellular;Fibroblasts;Generations;genetic deafness;Goals;Grant;Health;Heart Diseases;helicase;Human;Immune response;Immunology;Infection;Influentials;Inherited;Innate Immune Response;Innate Immune System;Inner mitochondrial membrane;innovation;Interferon Type I;Ion Channel;Joints;knock-down;Knockout Mice;Knowledge;Laboratories;Lead;Leigh Disease;Lipids;Liver diseases;Malignant Neoplasms;Mammalian Cell;Mass Spectrum Analysis;Mediating;Membrane;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;mitochondrial dysfunction;mitochondrial membrane;Mitochondrial Proteins;Mitochondrial RNA;Modeling;Molecular;mouse model;Mus;mutant;Mutation;Nervous System Disorder;Neurodegenerative Disorders;novel;Nuclear;Nucleic Acids;Outer Mitochondrial Membrane;Paper;pathogen;Pathologic;Pathway interactions;Patients;Pattern;Peptides;Physiological;Physiology;Point Mutation;Polyribonucleotide Nucleotidyltransferase;Process;prohibitin;Proteins;Publications;Publishing;Qualifying;Reagent;receptor;Research;response;Rest;RNA;RNA metabolism;Role;sensor;Signal Pathway;Signal Transduction;Specificity;Stress;Testing;trafficking;Training;Type I Interferonopathy;Untranslated RNA;Work

PROJECT_TITLE: RNA trafficking in mitochondria

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

PHR: Project Narrative We have recently found an average 54% increase in the number of hypocretin (orexin) producing neurons and a 32% shrinkage of these neurons in human heroin addicts. This is the largest change that has been reported in neuronal morphology in opiate addiction. We plan to determine the cause of this change and test the hypothesis that this increase causes, and can be manipulated to prevent or attenuate, the opiate withdrawal syndrome.

PI_NAMEs: SIEGEL, JEROME M (contact)

PROGRAM_OFFICER_NAME: MOORE, HOLLY MARIE

PROJECT_TERMS: Acute;addiction;Agonist;Amphetamines;Amygdaloid structure;Animals;antagonist;Area;Attenuated;Axon;Back;Behavior;Brain;Buprenorphine;Cell Count;Cell Size;Cells;Chronic;Clozapine;Data;Dendrites;density;designer receptors exclusively activated by designer drugs;Distal;dosage;Dose;Drug Addiction;Drug resistance;Dynorphins;Electric Capacitance;Excision;gamma-Aminobutyric Acid;Glutamates;Habenula;Half-Life;Heroin;Human;hypocretin;In Vitro;Injections;interest;Intrinsic drive;Knockout Mice;Location;locus ceruleus structure;Mediating;melanin-concentrating hormone;Membrane;Methadone;molecular marker;Morphine;morphine administration;Morphine Dependence;Morphology;Motor;Motor Cortex;Mus;Naloxone;Narcolepsy;Nature;neurogenesis;Neurons;noradrenergic;Opiate Addiction;opiate tolerance;Opioid;Opioid agonist;opioid epidemic;Opioid Receptor;opioid use;opioid withdrawal;optogenetics;Oxides;patch clamp;Pattern;Peptides;Pharmaceutical Preparations;Physiological;Physiology;Population;prevent;Production;Property;psychologic;receptor;Relapse;relapse prevention;Reporting;Resistance;response;Ritalin;Role;Saline;sensory cortex;Site;Sleep;Slice;Substance Withdrawal Syndrome;Substantia nigra structure;Symptoms;Synapses;Techniques;Testing;Thalamic structure;Therapeutic;Time;Transgenic Mice;Transgenic Organisms;Tyrosine 3-Monooxygenase;Ventral Tegmental Area;Viral Vector;Wild Type Mouse;Withdrawal;Withdrawal Symptom;Work;γ-hydroxybutyrate

PROJECT_TITLE: Role of hypocretin in opiate addiction and withdrawal

STUDY_SECTION: NNRS

STUDY_SECTION_NAME: Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section[NNRS]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Building Research Capacity at Institutions with Limited NIH Funding;Cystic Fibrosis;Emerging Infectious Diseases;Genetics;Infectious Diseases;Lung;Rare Diseases

ORG_CITY: KENNESAW

ORG_NAME: KENNESAW STATE UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative The structure and specificity of the Inhibitor of Vertebrate Lysozyme 2 (IVYp2) protein from the pathogenic bacterium Pseudomonas aeruginosa will be determined using an integration of structural biology, enzymology, and microbial genetics. This organism is often resistant to multiple classes of antibiotics and is responsible for significant mortality in patients with cystic fibrosis and opportunistic infections. Understanding IVYp2’s structure and functional specificity may enable the development of novel classes of antimicrobial drugs to fight multidrug resistant bacteria.

PI_NAMEs: LEEPER, THOMAS C (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: anti-microbial drug;Antibiotics;antimicrobial;Bacteria;Binding;Biochemical Pathway;Biochemistry;Biological Assay;Biophysics;Cell Wall;comparative;Complement;Complement Inactivators;Complex;crosslink;Crosslinker;Cystic Fibrosis;cystic fibrosis patients;Data Collection;Development;Drug Design;drug discovery;Enzymatic Biochemistry;Enzyme Inhibition;Enzyme Kinetics;Enzymes;ESKAPE pathogens;experimental study;Family;fighting;Future;Genes;Glycoside Hydrolases;graduate student;Human;Hydrolase;Hydrolysis;Immunity;In Vitro;in vivo;inhibitor;innovation;interest;Interferometry;knock-down;Knock-out;liquid chromatography mass spectrometry;Lytic;Mediating;member;Methods;Microbial Genetics;molecular recognition;mortality;Multi-Drug Resistance;multidrug-resistant Pseudomonas aeruginosa;Multiple Bacterial Drug Resistance;Muramidase;mutant;novel;novel drug class;Opportunistic Infections;opportunistic pathogen;Organism;paralogous gene;pathogen;pathogenic bacteria;Pathogenicity;Peptidoglycan;Phenotype;Plasmids;Predisposition;Property;Protein Isoforms;Proteins;Pseudomonas aeruginosa;repaired;Research;Resistance;Role;Small Interfering RNA;Specificity;structural biology;Structure;Training;Translational Repression;undergraduate student;Underrepresented Populations;Universities;Vertebral column;Work

PROJECT_TITLE: Comparative structural and functional analysis of Pseudomonas aeruginosa inhibitor of vertebrate lysozyme paralogs


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

ORG_CITY: MINNEAPOLIS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative This proposal will evaluate virus transmission and evolution in a new rodent model that aims to bridge natural and laboratory setting. This research will define virus and host features that impact intra and interspecies transmission helping to better understand the mechanisms of viral zoonosis.

PI_NAMEs: LANGLOIS, RYAN  (contact);WANG, ZHONGDE

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: 2019-nCoV;Acute;Address;Animal Model;Animals;Anti-viral resistance;Anti-viral Response;Astrovirus;Biological;Biological Models;Consumption;cross-species transmission;Data;Deer Mouse;Dose;Ebola;emerging virus;Evaluation;Event;Evolution;Excretory function;Exposure to;Failure;Family;genetic variant;global health;Habitats;Hamsters;Human;human migration;human morbidity;human mortality;human pathogen;Immunity;Immunocompromised Host;immunodeficiency;In Vitro;Individual;Infection;Interferons;Laboratories;Laboratory mice;Length;Measures;Methods;Middle East Respiratory Syndrome Coronavirus;model organism;Modeling;Murine hepatitis virus;Murine pneumonia virus;Mus;Natural Immunity;Norovirus;Oral;pathogen;pathogen spillover;pathogenic virus;Pathology;Physiological;Population;Population Dynamics;prevent;Rattus;Research;respiratory;Rodent;Rodent Model;Role;Route;Sendai virus;Shapes;Signal Transduction;STAT2 gene;success;System;Testing;Time;Tissues;tool;transcriptome sequencing;transmission process;Variant;Vertebrate Viruses;Viral;viral transmission;virome;Virus;Work;ZIKA;Zoonoses

PROJECT_TITLE: Natural model for evaluating within- and cross-species virus transmission

STUDY_SECTION: VPI

STUDY_SECTION_NAME: Viral Pathogenesis and Immunity Study Section [VPI]


ADMINISTERING_IC: NS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Epilepsy;Genetics;Neurodegenerative;Neurosciences

ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE Cognitive impairment is a major comorbidity of epilepsy and may be more disabling to patients than the seizures themselves. This proposal focuses on identifying the molecular and cellular mechanisms underlying memory impairment in temporal lobe epilepsy, which is the most common form of focal epilepsy and is often refractory to medications. Identifying these mechanisms will enable the development of targeted therapeutics to restore memory processes in patients.

PI_NAMEs: HO, VICTORIA  (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: Acute;Address;Adult;Affect;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Animals;Astrocytes;Automobile Driving;Autophagocytosis;axon growth;axonal sprouting;Behavior;Behavioral;Calcium;Candidate Disease Gene;carboxypeptidase C;Cathepsins;Cathepsins B;Cell Physiology;cell type;Cells;Characteristics;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Cognitive;comorbidity;Cysteine;Development;differential expression;Disabling;Disease;Electrophysiology (science);Environment;Epilepsy;Episodic memory;Exhibits;experimental study;extracellular;Family;Fire - disasters;Follow-Up Studies;Functional disorder;Gene Deletion;Genes;Genetic Transcription;Heterogeneity;Hippocampus;histological studies;Homeostasis;Human;Image;Impaired cognition;Impairment;improved;inhibitor;Interneurons;Knock-out;knockout gene;Link;Location;Maps;Mediating;Medical;Memory;Memory impairment;memory process;Microglia;Microscope;miniaturize;Molecular;mossy fiber;mouse model;Mus;Neurons;novel;Organism;Overlapping Genes;Partial Epilepsies;Pathogenicity;Pathologic;Pathologic Processes;Patients;Peptide Hydrolases;Performance;Pharmaceutical Preparations;Phase;Pilocarpine;post gamma-globulins;prevent;Property;Proteolysis;Quality of life;Refractory;Role;Seizures;side effect;single nucleus RNA-sequencing;spatial memory;Status Epilepticus;Synapses;targeted treatment;Temporal Lobe Epilepsy;Therapeutic Intervention;Time;Tissues;transcriptomics;Up-Regulation;water maze

PROJECT_TITLE: Cell Type-Specific Transcriptional Changes Underlying Memory Impairment in Temporal Lobe Epilepsy

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]


ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: Project Narrative  The central objective of this proposal is to develop a technological platform that harnesses light energy and biocatalysis to synthesize molecules of significant relevance to human life. We envision doing this by establishing cyanobacterial endosymbionts within yeasts cells, such that the endosymbiotic cyanobacteria provide ATP and assimilated carbon (generated from photosynthesis) to the yeast cells, which utilize it to produce biologically important natural products. The above endosymbiotic platform will allow us to couple the remarkable biosynthetic and biocatalytic potential of yeast to the photosynthetic ability of cyanobacteria to develop a sustainable and simple bioproduction platform to produce key precursors of FDA approved compounds, Artemisinin and Taxol.

PI_NAMEs: MEHTA, ANGAD  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Harnessing light and model endosymbiosis to produce natural products

STUDY_SECTION: SBCB

STUDY_SECTION_NAME: Synthetic and Biological Chemistry B Study Section[SBCB]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE - OVERALL Glioblastoma (GBM) remains one of the deadliest cancers. We will research how to improve the body’s immune cells recognition and destruction of GBM cells, by understanding how to better activate T cells in the tumor’s environment. Our group will perform a clinical trial of a novel personalized vaccine but also study how to make this even more efficacious in mouse models of GBM in order to get the body’s immune system to reject GBMs.

PI_NAMEs: CHIOCCA, E. ANTONIO (contact);REARDON, DAVID A

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Achievement;Address;anti-cancer;anti-PD-1;Attenuated;attenuation;biocomputing;Biometry;Brain Neoplasms;cancer type;CD4 Positive T Lymphocytes;CD8B1 gene;CDK4 gene;Cells;checkpoint receptors;Clinical;clinical application;clinical translation;Clinical Trials;cohort;Collaborations;Combination immunotherapy;Combined Vaccines;Complex;Computer Analysis;computerized tools;Data;Dendritic Cell Vaccine;effector T cell;Environment;epidermal growth factor receptor VIII;Failure;Genomics;Glioblastoma;Glucocorticoids;Goals;Human;Image;Immune;immune checkpoint blockade;Immune response;Immune system;Immunobiology;Immunophenotyping;immunoregulation;Immunosuppression;Immunotherapy;immunotherapy clinical trials;immunotherapy trials;improved;inhibitor;innovation;insight;KLRB1 gene;Long-Term Survivors;Malignant Neoplasms;Methods;Modality;Modeling;mouse model;Mus;neoantigen vaccine;neoantigens;neuro-oncology;Newly Diagnosed;novel;Oncolytic viruses;palliate;Pathway interactions;Patients;PD-1 blockade;Peptide Vaccines;Peptides;Phase Ib Trial;pre-clinical;preclinical trial;programmed cell death protein 1;programs;Regulation;Reporting;Research;Research Personnel;Research Project Grants;response;Safety;Sampling;Services;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Standardization;success;T cell infiltration;T memory cell;T-Cell Activation;T-Lymphocyte;Technology;Testing;Treatment Efficacy;tumor;Tumor Immunity;tumor-immune system interactions;Vaccines

PROJECT_TITLE: Understanding and Overcoming T cell Immunosuppression in Glioblastoma


ADMINISTERING_IC: OD

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Genetics;Human Genome;Women's Health Research

ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

ORG_STATE: NY

PHR: PROJECT NARRATIVE Fibrotic remodeling of extracellular matrix increases breast cancer risk and contributes to therapy resistance, but the underlying mechanisms remain unclear. This proposal will elucidate how interactions with fibrotic matrix regulate breast cancer DNA damage response and metabolism, key drivers of cancer progression and therapy response. Findings from these studies will enable novel treatment strategies to counter drug resistance and tailor therapeutic strategies specifically for patients with increased breast fibrosis.

PI_NAMEs: MOORE, ELIZABETH S (contact)

PROGRAM_OFFICER_NAME: TANDON, RITESH

PROJECT_TERMS: 3-Dimensional;Activation Analysis;animal model development;Antineoplastic Agents;Antioxidants;Basal Cell Cancer;Basal metabolic rate;Biologic Characteristic;Biological Assay;Biological Markers;Biological Models;Biological Sciences;Biophysics;Breast;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Model;Breast Cancer Patient;Breast Cancer Risk Factor;Breast Cancer therapy;Breast Cancer Treatment;Cancer Biology;cancer drug resistance;Cancer Prognosis;cancer therapy;career;career development;Cell Communication;Cell Cycle Checkpoint;Cellular Metabolic Process;chemotherapeutic agent;chemotherapy;Chromatin;Clinical;clinical care;clinical prognosis;Collagen;Collagen Type I;Complement;Core Facility;Data;Deposition;Detection;DNA biosynthesis;DNA crosslink;DNA Damage;DNA fiber assay;DNA Repair;DNA Repair Pathway;Drug resistance;Educational process of instructing;Engineering;Environment;experience;extracellular;Extracellular Matrix;Faculty;fatty acid oxidation;Fibrillar Collagen;Fibrosis;Future;Gene Expression Profiling;Genetic;Genetic Transcription;Genome Stability;Genus Hippocampus;Goals;Grant;Growth;Human;humanized mouse;Image;Immunofluorescence Immunologic;improved;In Vitro;in vivo;in vivo Model;innovation;interdisciplinary approach;interdisciplinary collaboration;Kinetics;Knowledge;Laboratories;Laboratory Animal Medicine;Link;Malignant Breast Neoplasm;mammary;Mammary Neoplasms;Manuscripts;mechanical properties;Mediating;Mentored Research Scientist Development Award;Mentors;Mentorship;Metabolic;metabolic phenotype;Metabolism;metabolomics;Methodology;Molecular;Molecular Genetics;mouse model;Mus;Mutagens;neoplastic cell;novel;Oncology;Oxidation-Reduction;Oxidative Stress;Pathway interactions;patient derived xenograft model;patient prognosis;Patients;pharmacologic;Pharmacotherapy;Phenotype;Phosphotransferases;physical science;Plasmids;Play;Preparation;Process;programs;Property;recruit;Regulation;repaired;replication stress;Reporter;Reporting;Research;Research Training;Resistance;resistance mechanism;Resolution;response;Role;Scientist;Signal Transduction;skills;Stromal Cells;Structure;Surgical Models;symposium;System;Technical Expertise;Techniques;Testing;Therapeutic;therapy resistant;tissue culture;Tissue Engineering;Training;transcriptome sequencing;translational physician;treatment response;treatment strategy;triple-negative invasive breast carcinoma;tumor;tumor metabolism;tumor microenvironment;tumor progression;tumorigenic;Universities

PROJECT_TITLE: Fibrotic extracellular matrix: uncovering its role in breast cancer genome stability and metabolic plasticity


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunization;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases;Skin Cancer;Vaccine Related

PHR: Narrative Project 1 will conduct a clinical trial to evaluate NeoVax, a novel individualized neoantigen vaccine platform developed at the Dana-Farber Cancer Institute, together with PD-1 blockade as a strategy to enhance anti-tumor immune responses and improve outcome for patients with newly diagnosed glioblastoma. The trial will focus on the evaluation of the impact of timing of administering PD-1 blockade relative to vaccination on the generation long-term T cell memory responses, which we think are important to clinical outcome.

PI_NAMEs: REARDON, DAVID A (contact)

PROJECT_TERMS: Address;Affect;anti-PD-1;anti-PD1 therapy;anti-tumor immune response;Antigen Targeting;antigen-specific T cells;Antigens;cancer infiltrating T cells;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cells;central tolerance;Clinical;Clinical Trials;Clonality;cohort;Collaborations;Combined Modality Therapy;Computer Analysis;Dana-Farber Cancer Institute;Data;design;Development;Diagnosis;Effector Cell;effector T cell;exhaustion;Exhibits;Gene Expression;Generations;Glioblastoma;high risk;Immune;Immune response;Immunize;Immunofluorescence Immunologic;immunogenic;immunogenicity;Immunologic Adjuvants;Immunologics;immunoregulation;Immunosuppression;Immunotherapeutic agent;Immunotherapy;Impact evaluation;improved outcome;long term memory;Malignant - descriptor;Malignant neoplasm of brain;Malignant Neoplasms;Manuscripts;Melanoma;Melanoma patient;Memory;mutant;Mutation;Nature;neoantigen vaccination;neoantigen vaccine;neoantigens;Newly Diagnosed;novel;Oncology;Operative Surgical Procedures;Outcome;palliative;Patient-Focused Outcomes;Patients;PD-1 blockade;Peptides;peripheral blood;Peripheral Blood Mononuclear Cell;Phase Ib Clinical Trial;Phase Ib Trial;Phenotype;Pilot Projects;Poly ICLC;Population;preservation;Production;programmed cell death protein 1;Radiation;Radiation therapy;Recurrence;Research Personnel;Resources;response;Rest;Safety;Sampling;Schedule;Signal Transduction;Specificity;Statistical Data Interpretation;T cell infiltration;T cell response;T memory cell;T-Cell Immunologic Specificity;T-Lymphocyte;Therapeutic;transcriptome;tumor;Tumor Antigens;tumor heterogeneity;tumor microenvironment;tumor specificity;Tumor Tissue;Tumor-infiltrating immune cells;Up-Regulation;Vaccinated;Vaccination;vaccine platform;vaccine strategy;Vaccines;Work

PROJECT_TITLE: Proj. 1 Targeting Tumor-Specific Neoepitopes for Glioblastoma Immunotherapy


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Immunization;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases;Vaccine Related

PHR: Narrative – Project 2 Project 2 will evaluate the ability of vaccination, oncolytic viruses or targeted therapies to improve Immune checkpoint blockade (CPB) therapy using immune competent GBM mouse models and determine how CPB timing and sequence in these combinatorial approaches affects T cell memory and therapeutic efficacy. These studies will inform rational selection of therapies for augmenting effects of CPB in GBM patients.

PI_NAMEs: CHIOCCA, E. ANTONIO (contact)

PROJECT_TERMS: Adult;Affect;anti-CTLA-4 therapy;anti-PD-1;anti-PD1 therapy;anti-tumor immune response;Biological Assay;Caring;CD8-Positive T-Lymphocytes;CDK4 gene;Cell Cycle;cell population study;cell type;Cells;checkpoint inhibition;Clinical Trials;combinatorial;Combined Modality Therapy;CTLA4 blockade;CTLA4 gene;Data;design;Development;efficacy testing;expectation;Future;Genetic Transcription;Glioblastoma;Goals;Harvest;Immune;immune checkpoint blockade;Immunocompetent;immunogenic cell death;Immunologic Memory;Immunologics;Immunosuppression;improved;insight;KLRB1 gene;Maintenance;Malignant neoplasm of brain;Malignant Neoplasms;Mediator;Memory;Modeling;mouse model;Mus;novel therapeutics;Oncolytic;Oncolytic viruses;Outcome;Pathway interactions;Patient-Focused Outcomes;Patients;PD-1 blockade;peptide vaccination;Peptide Vaccines;Phase I Clinical Trials;pre-clinical;Prognosis;programmed cell death ligand 1;programmed cell death protein 1;rational design;Regimen;response;Selection for Treatments;small molecule;T cell differentiation;T cell infiltration;T cell response;T memory cell;T-Cell Activation;T-Lymphocyte;targeted treatment;Testing;Therapeutic;Therapeutic Effect;Treatment Efficacy;tumor;tumor microenvironment;tumor-immune system interactions;Vaccination;Vaccine Therapy;Vaccines

PROJECT_TITLE: Proj. 2: Combining immune checkpoint blockade with T cell activation


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Biomedical Imaging;Data Science;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences;Pediatric

ORG_CITY: CHAPEL HILL

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative This project will empower neuroscience researchers with robust computational tools needed to study the early developing human brain in terms of tissue microstructure and white matter connection pathways using diffusion MRI. We will develop tools to tackle challenges speciﬁc to analyzing infant diffusion MRI data, including (i) com- plex microstructure arising from the interweaving of differentially oriented neurites (axons and dendrites) in the context of the extracellular matrix; and (ii) complex white matter ﬁber geometries, such as crossing, bending, and fanning. We will also create tools to cater to the big-data era need of dealing with data from multiple imaging sites with potential discrepancies in acquisition protocols and scanner behaviors, allowing intra- and inter-site variability to be reduced via data harmonization for consistent analysis with signiﬁcantly boosted statistical power.

PI_NAMEs: YAP, PEW-THIAN  (contact)

PROGRAM_OFFICER_NAME: BENNETT, YVONNE MARIE

PROJECT_TERMS: Address;Adult;Affect;Algorithms;Anatomy;Anisotropy;Award;Axon;Behavior;Big Data;Brain;brain tissue;Child;Communities;Complex;computerized tools;connectome;critical period;Crowns;Data;data harmonization;Dedications;deep learning;Dendrites;design;Development;developmental disease;Diffusion;diffusion anisotropy;Diffusion Magnetic Resonance Imaging;empowerment;Environment;Exhibits;Extracellular Matrix;Fiber;Geometry;Goals;Growth;Human;Image;imaging modality;improved;Infant;Life;Magnetic Resonance Imaging;Measurement;Methods;Minnesota;Myelin;myelination;Nature;Neurites;Neurodevelopmental Disorder;Neurologic;Neurosciences;North Carolina;Pathway interactions;Pattern;Process;Property;Protocols documentation;Research;Research Personnel;Signal Transduction;Site;Structure;Techniques;Time;Tissues;tool;tractography;Universities;white matter

PROJECT_TITLE: Computational Diffusion MRI for Studying Early Human Brain Development


ADMINISTERING_IC: HD

FUNDING_MECHANISM: RESEARCH CENTERS

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

ORG_CITY: IOWA CITY

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: The University of Iowa Intellectual and Developmental Research Center (Hawk-lDDRC) fully integrates basic and clinical research across the lifespan-from conception to adulthood-in a manner that is focused on the prevention, diagnosis, treatment, and amelioration of intellectual and development disabilities {IDDs), tailored to an underserved rural population. Researchers will collaboratively draw upon four Hawk-lDDRC Research Cores to examine the interaction of genetic/polygenic and epigenetic risk markers in autism and developmental delay using an innovative smartphone research application that enables direct family participation. The University of Iowa's long and distinguished history of lifespan research, access to a stable, non-transitory rural population, and the use of an interconnected telehealth system will facilitate longitudinal multi-generational research on IDDs that examines intrinsic and extrinsic risk factors in rural populations, as well as develops and conducts new treatments and clinical trials designed to reach individuals at all stages of life.

PI_NAMEs: ABEL, EDWIN TED G.;STRATHEARN, LANE  (contact)

PROGRAM_OFFICER_NAME: PARISI, MELISSA

PROJECT_TERMS: Adult;Affect;Animals;autism spectrum disorder;Basic Science;Behavior;biobank;Cellular Phone;Child;Child Abuse and Neglect;Clinical;clinical care;Clinical Research;Clinical Sciences;clinical translation;Clinical Trials;Clinical Trials Design;Cognitive;Collaborations;Communication;Communities;Conceptions;cost effective;Country;Development;Developmental Delay Disorders;Developmental Disabilities;Diagnosis;Disabilities experience;disability;Disability research;Down's Syndrome;early childhood;Early identification;Education;Educational workshop;effective intervention;Electrophysiology (science);Ensure;Environment;Environmental Risk Factor;Epigenetic Process;epigenetic regulation;exome;Family;Fostering;Foundations;Funding;Future;gene therapy;Genes;Genetic;Genetic Variation;genome sequencing;Genomics;Goals;Government Officials;Human;human old age (65+);Huntington Disease;improved;in utero diagnosis;Individual;Infrastructure;innovation;Intellectual and Developmental Disabilities Research Centers;Intellectual functioning disability;interdisciplinary collaboration;Interdisciplinary Communication;Interdisciplinary Study;Intervention;Iowa;Joints;Journals;Knowledge;Language Development;Leadership;Life;life span;Link;meetings;Mentors;Midwestern United States;Mission;multidisciplinary;neural circuit;Neurodevelopmental Disability;Neurosciences;Newsletter;novel;organizational structure;Parent-Child Relations;Patient Recruitments;pediatric patients;Phenotype;Policy Maker;pollutant;Population;Population Heterogeneity;Positioning Attribute;Pregnancy;premature;prenatal stress;Prevalence;prevent;Prevention;Prevention strategy;Productivity;programs;Publications;Recording of previous events;recruit;Reporting;Research;research facility;Research Personnel;Research Project Grants;Research Support;Resources;retention rate;Risk Factors;Risk Marker;RNA;Rural;Rural Population;rural setting;rural underserved;Scientist;Series;Services;social media;Structure;Talents;telehealth systems;Translational Research;treatment trial;Universities;web site;whole genome

PROJECT_TITLE: University of Iowa Hawkeye Intellectual and Developmental Disabilities Research Center (Hawk-IDDRC)


NIH_SPENDING_CATS: Aging;Brain Disorders;Disability Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric

PI_NAMEs: ABEL, EDWIN TED G. (contact)

PROJECT_TERMS: Adult;Advisory Committees;Area;Award;Basic Science;Budgets;Clinical;clinical care;Clinical Research;Clinical Sciences;Collaborations;Communication;Communities;Conceptions;cost effective;Development;Developmental Disabilities;Diagnosis;disability;Education;Education and Outreach;Educational workshop;Ensure;Environment;Evaluation;experience;Family;Fellowship;Foundations;Funding;Genetic;Government;Government Officials;Grant;human old age (65+);improved;innovation;Institution;Intellectual and Developmental Disabilities Research Centers;Iowa;K-Series Research Career Programs;Leadership;life span;meeting reports;meetings;Mentored Clinical Scientist Development Program;Mentors;Methods;Mission;multidisciplinary;National Institute of Child Health and Human Development;Nature;Newsletter;next generation;operation;organizational structure;Physicians;Policy Maker;Population;Population Heterogeneity;Prevention;Privatization;Productivity;programs;Progress Reports;Publications;Quality Control;recruit;Research;research data dissemination;research facility;Research Personnel;Research Project Grants;Research Support;Resources;Risk Marker;Rural;Rural Population;satisfaction;Scientist;Series;Services;social media;Students;Surveys;Training;Translational Research;translational research program;Universities;Vision;web site;Work

PROJECT_TITLE: Core A: Administrative Core


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Neurosciences;Rare Diseases

PHR: Project Narrative This project focuses on the role of the CD161-CLEC2D pathway in inhibiting T cell function in GBM. The major goal of this study is to define the molecular mechanisms by which CD161 signaling inhibits T cell function in GBM and to determine the therapeutic significance of targeting the CD161 – CLEC2D interaction.

PI_NAMEs: WUCHERPFENNIG, KAI W (contact)

PROJECT_TERMS: anti-PD1 antibodies;Antibodies;Blocking Antibodies;brain tissue;C Type Lectin Receptors;cancer infiltrating T cells;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Line;Cell Physiology;Cell surface;Cell-Mediated Cytolysis;Cells;Cellular Immunity;Clinical Trials;Clonal Expansion;Clone Cells;Collaborations;Color;Combined Modality Therapy;cytokine;cytotoxic;cytotoxicity;Data;Diagnosis;Dinoprostone;Effector Cell;effector T cell;exhaust;experimental study;Flow Cytometry;Gene Expression;Gene Expression Profile;Genes;genetic approach;Glioblastoma;Glioma;Goals;Human;humanized mouse;Immune;Immunocompetent;Immunodeficient Mouse;Immunohistochemistry;Immunosuppression;Immunotherapy;implantation;interest;Interferon Type II;KLRB1 gene;Label;Length;Ligands;Malignant Neoplasms;Mediating;Messenger RNA;Molecular;Monoclonal Antibodies;mouse model;Mus;Myeloid Cells;Natural Killer Cells;neoantigen vaccine;neoplastic cell;Operative Surgical Procedures;overexpression;participant enrollment;Pathway interactions;Patients;Peptide Vaccines;Peptide/MHC Complex;Phase;Population;population based;programmed cell death ligand 1;programmed cell death protein 1;programs;Proteins;receptor;receptor expression;Relapse;response;Role;Sampling;Signal Transduction;single-cell RNA sequencing;Spatial Distribution;T cell infiltration;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;Therapeutic;transcriptome sequencing;tumor;Tumor Immunity;WFDC2 gene;Work

PROJECT_TITLE: Proj. 3: Immunosuppressive circuits in T cells and other immune cells in GBM patients enrolled in clinical trials


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

PHR: PROJECT NARRATIVE Glioblastome multiforme (GBM) is a deadly form of brain cancer that is not benefitting from current advances in immune-based therapies. This could be due to the inherent state of immune suppression that serves to prevent unwanted inflammation in the brain. The proposed studies will advance our knowledge of how immunoregulatory cytokine signaling acts together with steroid hormone signaling to suppress anti-tumor immune responses in GBM.

PI_NAMEs: KUCHROO, VIJAY K. (contact)

PROJECT_TERMS: anti-CTLA4;anti-PD-1;anti-tumor immune response;Automobile Driving;biocomputing;Brain;cancer immunotherapy;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Physiology;Cells;Cerebral Edema;checkpoint receptors;Clinical Management;Clinical Trials;Collaborations;Complement;CTLA4 gene;cytokine;Cytokine Signaling;Data;Dexamethasone;Dose;effector T cell;Excision;exhaustion;Failure;fighting;Functional disorder;Gene Expression;Genes;Glioblastoma;Glucocorticoids;hormonal signals;Human;Immune;immune cell infiltrate;immune checkpoint;immune checkpoint blockade;Immune response;Immune system;immunoregulation;Immunosuppression;Immunosuppressive Agents;Immunotherapy;improved;Individual;Inflammation;Investigation;KLRB1 gene;Knowledge;Malignant neoplasm of brain;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Mediator;Melanoma;Modeling;mouse model;Mus;novel;Operative Surgical Procedures;Pathway interactions;Patients;Play;Population;Pre-Clinical Model;prevent;programmed cell death protein 1;programs;receptor;receptor expression;receptor function;Regulatory T-Lymphocyte;Renal Carcinoma;Reporter;Resistance;response;RNA;Role;Signal Transduction;single-cell RNA sequencing;Site;Statistical Data Interpretation;steroid hormone;success;synergism;T-Lymphocyte;Testing;Therapeutic;Time;Treatment outcome;tumor;tumor growth;tumor microenvironment;Tumor-Infiltrating Lymphocytes;Vaccines

PROJECT_TITLE: Proj 4: Triggers for the Induction of T Cell Dysfunction on T cells in Glioblastoma


NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Brain Disorders;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Depression;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Mental Illness;Neurosciences;Pediatric;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID;Prevention;Social Determinants of Health;Suicide

ORG_CITY: PITTSBURGH

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative. The proposed study will advance our understanding of the impact of COVID-19 infection on risk for psychopathology in youth and its impact on dysregulations in inflammatory and HPA axis markers, which will help identify youth at highest risk following COVID-19 infection who can then be targeted for closer monitoring and interventions. It will also improve our understanding of the biological mechanisms implicated in risk for psychopathology following COVID-19 infection and guide the development of new treatment approaches. The results obtained from this study will also extend to other types of infections and is essential to inform our preparedness efforts for future epidemics and pandemics, which are inevitable and on the rise.

PI_NAMEs: MELHEM, NADINE M. (contact)

PROGRAM_OFFICER_NAME: ZEHR, JULIA L

PROJECT_TERMS: Acute;Adolescent;Adult;Age;aged;Antibodies;Anxiety Disorders;Biological;Biological Markers;Blood;C-reactive protein;Cessation of life;Characteristics;Child;Chronic;Chronic Disease;chronic infection;Clinical;Cognitive;cognitive function;COVID-19;COVID-19 impact;COVID-19 pandemic;COVID-19 severity;cytokine;Data;Development;Domestic Violence;Emerging Communicable Diseases;Family;Family history of;Feeling suicidal;Frequencies;future epidemic;future pandemic;Genes;Goals;Hair;high risk;Hydrocortisone;hypothalamic-pituitary-adrenal axis;Immune response;Impaired cognition;improved;Incidence;Individual;Infection;Inflammation;Inflammatory;Influenza;Interleukin-6;Intervention;Job loss;Measures;Mental Depression;Mental disorders;Mental Health;Messenger RNA;Monitor;Morbidity - disease rate;mortality;novel therapeutic intervention;pandemic disease;pandemic impact;Participant;physical symptom;post SARS-CoV-2 infection;protective factors;Psychiatric Diagnosis;psychiatric symptom;Psychiatric therapeutic procedure;Psychopathology;psychosocial;Public Health;Race;Readiness;Recording of previous events;recruit;Reporting;Respiratory Tract Infections;Risk;Risk Factors;Salivary;SARS-CoV-2 infection;Schools;Severities;sex;Socioeconomic Status;stressor;suicidal behavior;suicidal risk;Testing;Time;TNF gene;transmission process;Vaccination;Youth

PROJECT_TITLE: COVID-19, Inflammation and HPA axis activity, and Risk for Psychopathology in Youth

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BP-P(02)M]


NIH_SPENDING_CATS: Infectious Diseases

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: Project Narrative Cryptococcus neoformans is an environmental fungus that can cause life-threatening infections in the lungs and brain of individuals with defects in their immune system. This project seeks to determine the mechanisms by which the fungus can actively inhibit the response of immune cells in the lungs and prevent resolution of the infection. This information will enable the development of therapies that can enhance the immune system to specifically help patients clear the fungus and avoid serious infectious complications.

PI_NAMEs: HEUNG, LENA J (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: adaptive immune response;Antifungal Therapy;Antigen-Presenting Cells;Autoimmunity;Bacteria;Binding;Bone Marrow;Brain;CD8-Positive T-Lymphocytes;Cell Surface Receptors;Cells;Complex;Cryptococcosis;Cryptococcus;Cryptococcus neoformans;Cryptococcus neoformans infection;cytokine;cytotoxic CD8 T cells;Data;Death Rate;Defect;Dendritic Cells;Development;Disease Progression;Dissection;fungicide;fungus;Genetic;Goals;HIV/AIDS;Immune;Immune response;Immune system;Immunity;Immunocompromised Host;immunoregulation;improved;in vitro Model;in vivo;Individual;Infection;Inflammatory;Inflammatory Response;Inhalation;Intervention;ITAM;Life;Lung;Macrophage;Malignant Neoplasms;Mediating;Meningoencephalitis;Modeling;Molecular;monocyte;mortality;mouse model;Mus;Mycoses;Myelogenous;Myeloid Cells;Natural Killer Cells;novel;novel strategies;Organ Transplantation;Outcome;pathogenic fungus;Patients;permissiveness;Phagocytosis;Play;Populations at Risk;prevent;Production;Proliferating;Proteins;receptor;Receptor Signaling;recruit;Regimen;Regulation;Repression;Resolution;response;Role;Signal Pathway;Signal Transduction;Solid;T cell response;T-Cell Proliferation;therapy development;TNF gene;Toll-like receptors;tool;TREM2 gene;uptake

PROJECT_TITLE: DAP12 and the host response to cryptococcosis


PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Disability Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Prevention;Social Determinants of Health

PI_NAMEs: BASSUK, ALEXANDER G (contact)

PROJECT_TERMS: Acceleration;Address;Adolescence;Adult;adverse pregnancy outcome;Affect;Age;Architecture;Area;autism spectrum disorder;Basic Science;biobank;Bioinformatics;Biology;care systems;Caregivers;Caring;Clinic;Clinical;Clinical Data;clinical practice;Clinical Research;clinical translation;Clinical Trials;cohort;Collaborations;Conceptions;Consent;Control Groups;cost effective;Country;critical period;Data;data access;Data Mart;design;Development;Diagnosis;Disability research;electronic consent;Etiology;Family;Funding;Genetic study;Geography;Hand;Healthcare Systems;human subject;improved;Individual;Infrastructure;Inpatients;Intellectual and Developmental Disabilities Research Centers;Intellectual functioning disability;International;Intervention;Iowa;Laboratories;Life;life span;manufacture;Mental disorders;Mission;Molecular;novel;organizational structure;Outcomes Research;Participant;patient population;Patient Recruitments;Patients;perinatal period;Personal Satisfaction;Pharmaceutical Preparations;Population;Population Heterogeneity;Pregnancy;Pregnancy Outcome;prenatal;Prevention;Primary Care;prospective;Provider;Puberty;Race;recruit;Research;research clinical testing;Research Infrastructure;Research Personnel;research study;Resistance;Resources;Risk Assessment;Role;Rural;rural area;Rural Population;Schools;Services;Site;Source;synergism;Testing;Translating;Translational Research;Underserved Population;Universities;urban area;Work

PROJECT_TITLE: Core B: Clinical Translational Core


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Immunization;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases;Vaccine Related

PHR: Narrative The Molecular Immunology Core provides centralized single-cell RNA-sequencing expertise to characterize immune cells and malignant cells in glioblastoma. We will provide know-how to profile both clinical samples and mouse models with these techniques, serving all projects.

PROJECT_TERMS: Animal Model;anti-PD1 antibodies;antigen-specific T cells;Blood;Brain Neoplasms;cancer cell;cancer infiltrating T cells;Cell Separation;Cells;Clinical;Clinical Trials;Clonal Expansion;Combination immunotherapy;Complex;conventional therapy;Data;Data Set;data sharing;Diagnosis;DNA Sequencing Facility;Ecosystem;Ensure;Epigenetic Process;Equipment;Experimental Models;Flow Cytometry;Gene Expression;Genetic;genetic information;Genetic Transcription;Genomics;Genotype;Glioblastoma;Goals;Heterogeneity;Human;Human Resources;Immune;Immunologics;Immunosuppression;Immunotherapy;Individual;Knowledge;Length;Malignant Neoplasms;Methods;Molecular Immunology;mouse model;Myeloid Cells;neoantigen vaccine;neoantigens;novel therapeutic intervention;Operative Surgical Procedures;participant enrollment;Pathway interactions;Patients;Peptide Vaccines;Phase;Population;Premalignant Cell;programs;Quality Control;Reagent;Recurrence;Recurrent tumor;Regulatory Pathway;Relapse;Reproducibility;Research Personnel;Resolution;Resources;Sampling;Services;single cell technology;single-cell RNA sequencing;Specimen;Standardization;success;T cell infiltration;T-Lymphocyte;Techniques;Technology;technology platform;Testing;tool;Transcript;transcriptome;tumor

PROJECT_TITLE: Core 1: Tumor Processing and Single Cell RNA sequencing Core


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because the early-stage preclinical validation of therapeutic leads that target novel pathways of energy homeostasis and nutrient metabolism offers promise for the management of obesity-related disorders. The proposed studies are relevant to the mission of the NIDDK because they are expected to identify new lead compounds for the treatment of non-alcoholic fatty liver disease.

PI_NAMEs: COHEN, DAVID E. (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Acyl Coenzyme A;Address;Adipocytes;Adipose tissue;Biological;Biological Assay;Biophysics;Brown Fat;Calories;Cell Culture Techniques;Cells;Consumption;Coupled;cytotoxicity;Data;design;Development;Disease;Dose;Drug Kinetics;drug-like compound;efficacy testing;Energy Metabolism;Enzymatic Biochemistry;Enzymes;experimental study;fatty acid metabolism;fatty acid oxidation;Fatty Acids;Fatty Liver;Genes;glucose metabolism;glucose production;Goals;Hepatic;Hepatocyte;high throughput screening;Homeostasis;Human;improved;In Vitro;in vivo evaluation;Inflammation;Inflammation Mediators;inhibitor;Intervention;Lead;lead optimization;Left;Lipid Binding;Lipids;Liver;Mediating;Medical;Medication Management;member;Metabolic;Mission;Mitochondria;Modality;mouse model;Mus;National Institute of Diabetes and Digestive and Kidney Diseases;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;novel therapeutics;nutrient metabolism;obesity management;Outcome Study;Overnutrition;parent grant;Pathogenesis;Pathogenicity;Pathway interactions;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Physiological;Positioning Attribute;pre-clinical;Prevalence;prevent;Production;Property;Public Health;Regulation;Research;Resistance;Role;Route;Safety;Schedule;small molecule;small molecule inhibitor;Specificity;structural determinants;Structure;Structure-Activity Relationship;Testing;Therapeutic;therapeutic lead compound;Thermogenesis;Tissues;Triglycerides;Validation

PROJECT_TITLE: Them1 Inhibitors for the Management of Non-Alcoholic Fatty Liver Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-EMS-H(55)R]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Neurosciences;Rare Diseases

PHR: PROJECT NARRATIVE— Core 2 Biocomputation and Biostatistics The goal of Core 2 Biocomputation and Biostatistics is to assure that all experiments conducted through this P01 focused on T cell activation and attenuation in glioblastoma multiforme have access to state-of-the-art computational support for the single cell RNA sequencing analyses which are critical to each of the projects, and to state-of-the-art statistical support for design and analysis of all clinical, correlative, murine, and basic laboratory projects. This assures that the work of this GBM P01 will be robust and reproducible, and thereby contribute to understanding the changes in T cell activation and attenuation that result from immunologic interventions in GBM.

PI_NAMEs: NEUBERG, DONNA S. (contact)

PROJECT_TERMS: Address;Algorithms;Animal Experiments;Animal Model;Animals;attenuation;B-Lymphocytes;Basic Science;biocomputing;Biological Assay;Biometry;Biostatistics Core;Cell Communication;Cell Line;cell type;Cells;Classification;Clinical;Clinical Research;Clinical Trials;clinically relevant;Clonality;Clone Cells;Collaborations;computational pipelines;computerized data processing;Correlative Study;Data;Data Analyses;data sharing;design;Ecosystem;Ensure;Experimental Designs;experimental study;Genes;Genetic;genetic manipulation;Genetic Variation;Genomics;Glioblastoma;Goals;Human;human data;immunological intervention;Immunosuppression;Immunotherapy;Individual;insight;Intervention;Investigation;Laboratories;laboratory experiment;Lead;Malignant - descriptor;Maps;Measurement;mouse model;Mus;Noise;Non-Malignant;Patients;Peer Review;Physiological;power analysis;Prediction of Response to Therapy;Process;profiles in patients;programs;Reproducibility;Resources;Scheme;single nucleus RNA-sequencing;single-cell RNA sequencing;Specimen;T-Cell Activation;T-Lymphocyte;Techniques;temporal measurement;treatment response;tumor;tumor-immune system interactions;Visualization;Work

PROJECT_TITLE: Core 2: Biocomputational and Biostatistics Core


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: m6Am is one of the most abundant epitranscriptomic modifications, occurring on the cap-proximal adenosine in eukaryotic and viral mRNAs. However, little is known about the functional consequences of m6Am on mRNAs. In this study we will use our recent identification of the m6Am methyltransferase, PCIF1, to decipher the role of m6Am in discriminating self from non-self RNA in viral infections in vitro, in cell culture, and in animals.

PI_NAMEs: GREER, ERIC LIEBERMAN;WHELAN, SEAN PJ (contact)

PROJECT_TERMS: 5'-exoribonuclease;Adenosine;Affect;Animals;Anti-viral Response;Binding;Biochemical;Biological;C-terminal;Cell Culture Techniques;Cell Nucleus;Cells;Cytoplasm;Data;Digestion;Discrimination;Elements;Embryo;Ensure;epitranscriptomics;Evolution;Fibroblasts;Genes;Genetic;Genomic approach;Goals;Growth;Guanine;Hela Cells;In Vitro;in vivo;Infection;Interferon-beta;Interferons;Knock-out;Literature;Mediating;Messenger RNA;Methods;Methylation;Methyltransferase;Modification;mRNA capping;mRNA Export;mRNA Stability;mRNA Translation;Mus;mutant;Nuclear Export;Phenotype;Phosphorylation;Positioning Attribute;Publishing;Reagent;Ribose;Ribosomes;RNA;RNA methylation;RNA Polymerase II;RNA Sequences;RNA Viruses;Role;Structure;System;Testing;tool;Transcript;transcription factor TFIIH;Transcription Initiation Site;transcriptome;Translations;Vesicular stomatitis Indiana virus;Vesicular stomatitis virus M protein;Viral;Viral Pathogenesis;viral RNA;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Cap specific N6 methylation of viral mRNA by the cellular methyltransferase PCIF1

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


PHR: Narrative Core 3 will provide services to Projects 2, 3 and 4 by providing well characterized mouse GBM cells and by performing the intracranial implantation procedures to establish GBMs in mouse brains. Monitoring of GBM growth will be performed utilizing small animal MRIs and bioluminescence imaging.

PROJECT_TERMS: Animals;bioluminescence imaging;Brain;Cells;Clinical;Collaborations;comparative;Development;Engineering;Ensure;exome sequencing;experimental study;Glioblastoma;Goals;Grant;Growth;Human Resources;Image;immune checkpoint;Immune checkpoint inhibitor;Immunology;Immunosuppression;Immunotherapy;Implant;implantation;Implantation procedure;improved;Individual;Infection;Institution;interest;Intracranial Neoplasms;Investigational Therapies;Luciferases;Magnetic Resonance Imaging;Maintenance;member;Modeling;Modification;Molecular;Monitor;Mouse Cell Line;Mus;neoantigens;Oncolytic;Oncolytic viruses;Operative Surgical Procedures;Performance;programs;Quality Control;receptor;repository;Reproducibility;Research;Research Personnel;Research Project Grants;Resistance;Resources;Sampling Biases;serial imaging;Service provision;Services;Signal Transduction;Simplexvirus;T-Lymphocyte;Technical Expertise;Techniques;Testing;Time;Transgenes;tumor;Tumorigenicity;United States National Institutes of Health;Validation

PROJECT_TITLE: Core 3: Mouse GBM models and Imaging Core


NIH_SPENDING_CATS: Aging;Biotechnology;Brain Disorders;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health

PI_NAMEs: SMITH, RICHARD J.H. (contact)

PROJECT_TERMS: Adopted;Adult;Aging;analysis pipeline;analytical method;Animal Model;Animals;Area;Basic Science;Bioinformatics;bioinformatics resource;Biological;Biological Assay;Biological Models;Calibration;Cell Nucleus;Cells;Certification;ChIP-seq;Chromium;Clinical Research;clinical translation;Code;cognitive function;Collection;Communities;Complement;Complex;Computer Analysis;Computer software;computing resources;Conceptions;cost effectiveness;Country;Data;Data Analyses;data format;Data Pooling;Data Set;Development;Diagnosis;differential expression;Disability research;DNA Methylation;DNA methylation profiling;drug repurposing;Education;Educational workshop;Epigenetic Process;epigenomics;Equipment;exome sequencing;Exons;experience;experimental study;Funding;Genetic;Genome;genome sequencing;genome-wide;genomic data;Genomics;Genotype;High-Throughput Nucleotide Sequencing;Human;Human Genetics;human model;human tissue;innovation;insight;Intellectual and Developmental Disabilities Research Centers;Intellectual functioning disability;Iowa;Laboratories;Leadership;life span;Machine Learning;Manuals;Meta-Analysis;Methodology;Methylation;methylome;Microarray Analysis;Mus;neurodevelopment;novel;Organization administrative structures;Persons;polygenic risk score;Prevention;programs;Protein Isoforms;Quality Control;Rattus;recruit;Reproducibility;Research;Research Personnel;Research Project Grants;research study;Resources;Ribosomes;Risk;Rural Population;Saliva;Sampling;service utilization;Services;single cell sequencing;single nucleus RNA-sequencing;single-cell RNA sequencing;Source;Standardization;synergism;Systems Development;Technology;Tissues;tool;Training;training opportunity;transcriptome;transcriptome sequencing;United States National Institutes of Health;Universities;Variant;whole genome;Zebrafish

PROJECT_TITLE: Core C: Developmental Genomics-Epigenetics Core


ORG_CITY: PORTLAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Energy metabolism and fertility in females are inextricably linked, and 17β-estradiol (E2) is critically involved in the regulation of both, in part through its action on kisspeptin neuronal circuits. Hypoestrogenic states often lead to obesity and subsequently obesity-related adverse health conditions such as metabolic syndrome. Our project will contribute significantly to the understanding of how the hypothalamus integrates E2 and metabolic hormonal cues to regulate energy homeostasis, which will help to develop novel therapeutic treatments.

PI_NAMEs: KELLY, MARTIN JEFFREY (contact);RØNNEKLEIV, OLINE KARIN

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Address;Adult;Agonist;Animals;Appetite Stimulants;Attenuated;Biophysics;Brown Fat;Castration;Clustered Regularly Interspaced Short Palindromic Repeats;Coupled;Cues;Development;Down-Regulation;Dynorphins;Eating;Electrophysiology (science);Energy Metabolism;Estradiol;Estrogen Receptors;estrogenic;Estrogens;Female;Fertility;Frequencies;Genetic;Glutamate Receptor;Glutamates;Goals;Gonadal Steroid Hormones;Health;Homeostasis;Hormonal;hormonal signals;Hypothalamic structure;Insulin;interdisciplinary approach;KISS1 gene;knock-down;Leptin;Link;Maintenance;male;Measures;Medial Dorsal Nucleus;Mediating;Membrane;Messenger RNA;Metabolic;Metabolic hormone;Metabolic syndrome;Metabotropic Glutamate Receptors;Molecular;Molecular Biology;mRNA Expression;Neurokinin B;neuronal circuitry;neuronal excitability;Neurons;neuropeptide Y;Neuropeptides;neurophysiology;Neurotransmitters;novel therapeutics;Obesity;optogenetics;paraventricular nucleus;parvocellular;Peptides;Physiology;presynaptic;Pro-Opiomelanocortin;programs;Property;Puberty;receptor;reduced food intake;Regulation;Reproduction;reproductive success;Research;Role;Sex Differences;Signal Pathway;Signal Transduction;Structure of dorsomedial hypothalamic nucleus;Structure of nucleus infundibularis hypothalami;Synapses;Synaptic Transmission;Temperature;tool;transmission process;vesicular glutamate transporter 2;Whole-Cell Recordings;women's treatment

PROJECT_TITLE: Cross-talk between Estrogen and Metabolic Hormone Signaling in Kisspeptin Neurons

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]


ED_INST_TYPE: HOSPITALS

ORG_CITY: HOUSTON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: PROJECT NARRATIVE Diabetic nephropathy remains a major unmet medical need, prompting intensive efforts to identify molecular drivers of the disease for which targeted therapies might be developed. The current application introduces an exciting new area of research into the pathogenesis of diabetic kidney disease by implicating the essential regulatory role of long non-coding RNAs in the development of diabetic kidney disease.

PI_NAMEs: DANESH, FARHAD R (contact)

PROGRAM_OFFICER_NAME: NIHALANI, DEEPAK

PROJECT_TERMS: Ablation;Address;Area;Binding Proteins;Biological;Biological Markers;Carbohydrates;Cardiovascular Pathology;Cell Nucleus;Characteristics;Clinical Research;Communication;Complement;Cytoplasm;Data;db/db mouse;Development;Diabetes Mellitus;diabetic;Diabetic mouse;Diabetic Nephropathy;Diagnostic;Disease;expectation;Experimental Models;Funding;Future;Gene Expression;genetic approach;Genetic Transcription;Glucose;Goals;Homeostasis;in vivo;Investigation;Investments;Kidney;Label;Laboratories;Malignant Neoplasms;Mediating;Medical;Medicine;MicroRNAs;Mitochondria;mitochondrial fitness;mitochondrial metabolism;Modeling;Molecular;mutant mouse model;neurological pathology;new therapeutic target;next generation;Non-Insulin-Dependent Diabetes Mellitus;Nuclear;Nucleotides;Open Reading Frames;Organelles;overexpression;Pathogenesis;Pathologic;Pathology;Patients;Peptides;podocyte;PPAR gamma;Process;Property;protective effect;Proteins;Publishing;Regulation;Research;response;Response Elements;RNA;Role;targeted treatment;Techniques;Therapeutic;therapeutic target;Tissues;Transcript;transcription factor;Transgenic Mice;Translating;TUG1 gene;Untranslated RNA;Work

PROJECT_TITLE: MicroRNA In Diabetic Nephropathy

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Disability Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

PI_NAMEs: NOPOULOS, PEGGY C (contact)

PROJECT_TERMS: Address;Adult;Age;analysis pipeline;Animal Model;Animals;Behavior;Behavioral;Behavioral Assay;Bioinformatics;biomedical imaging;Brain;Brain imaging;Child;Clinic;Clinical;Clinical Research;Clinical Trials;Cognition;Cognitive;cognitive change;Collaborations;Communities;Conceptions;cost effectiveness;Country;Data;data management;Data Set;design;Development;Diagnosis;disability;Disability research;Elderly;Ensure;Equipment;Experimental Designs;experimental study;Family;flexibility;Fostering;Funding;Human;human model;Image;Image Analysis;Imaging Device;Imaging Techniques;Individual;Intellectual and Developmental Disabilities Research Centers;Intellectual functioning disability;Investigation;Iowa;Knowledge;Laboratories;laboratory experience;Laboratory Finding;Laboratory Personnel;Learning;life span;Manuals;Memory;Metabolism;Modality;Monitor;neonate;neural circuit;neuroimaging;Neurosciences;novel;Physiologic pulse;Prevention;Process;programs;Protocols documentation;quality assurance;Research;Research Personnel;Research Project Grants;research study;Research Support;Resources;rural area;Rural Population;Scientist;service utilization;Services;Sleep;Social Interaction;Specific qualifier value;Structure;synergism;System;Technology;tool;Training;Transcranial magnetic stimulation;Translating;translational approach;Translations;Universities

PROJECT_TITLE: Core D: Neurocircuitry and Behavior Core


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Biotechnology;Natural Products

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE To better develop new medicines to treat human disease, we rely on advances in synthetic chemistry to better produce molecules for their studies in biomedical applications. This proposal seeks to expand the available synthetic toolkit by delving into the untapped potential of enzymes as biocatalysts for organic synthesis. By taking two approaches, an approach that seeks to repurpose known biosynthetic enzymes to furnish diverse products, and a second approach that seeks to discover hidden non-native reactivities of enzymes, this research will offer expedient, mild and stereoselective routes to chemical structures that have immediate therapeutic potential.

PI_NAMEs: SMITH, KENDRICK LINWOOD (contact)

PROGRAM_OFFICER_NAME: GIBBS, KENNETH D

PROJECT_TERMS: Active Sites;Address;Amino Acids;Anabolism;antimicrobial;Antineoplastic Agents;Bioinformatics;chemical reaction;Chemical Structure;chemical synthesis;Chemicals;Chemistry;cofactor;Complement;Complex;Coupled;Cyclization;Cytochrome P450;design;Development;drug discovery;Environment;Enzymes;Exhibits;experience;Family;Flavins;functional group;halogenation;high throughput technology;Human;human disease;Human Pathology;Hydroxylation;In Vitro;inhibitor;innovation;Lead;Learning;lens;Libraries;Maps;marine;Medicine;Mentors;metalloenzyme;Methodology;Methods;Mixed Function Oxygenases;Modernization;Molecular;Molecular Biology Techniques;Natural Products;Nature;non-Native;novel;novel therapeutics;Organic Synthesis;Organism;oxidation;Pathway interactions;Pharmaceutical Preparations;Pharmacologic Substance;Phase;Porifera;Preparation;Protein Engineering;Proteins;Proteomics;Pyridoxal Phosphate;Reaction;Research;Route;scaffold;screening;Site;small molecule;Synthesis Chemistry;Techniques;Terpenes;Therapeutic;tool;Training;Translating;Translations;Tropolone;Veins;Viral

PROJECT_TITLE: Designing chemoenzymatic approaches to biologically active molecules enabled by enzyme library screening


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Prevention;Social Determinants of Health

PI_NAMEs: STRATHEARN, LANE  (contact)

PROJECT_TERMS: 3 year old;adolescent with autism spectrum disorder;Affect;Age;Anxiety;Autism Diagnosis;autism spectrum disorder;autistic behaviour;autistic children;Behavior;Birth;Blood;Brain;Cellular Phone;Child;Clinical assessments;clinical translation;cognitive development;cohort;Collection;cost estimate;Data;Day Care;Development;Developmental Delay Disorders;Developmental Disabilities;Devices;Diagnosis;disability;disability risk;Disease;DNA;DNA Methylation;Dryness;Early Intervention;Ecological momentary assessment;educational atmosphere;Emotional;Enrollment;Environment;Environmental Risk Factor;Epigenetic Process;Ethnic Origin;Etiology;Exclusion;experience;Family;Genetic;Genetic Predisposition to Disease;Genetic study;Genomics;Goals;Home;Individual;innovation;Intellectual and Developmental Disabilities Research Centers;Intellectual functioning disability;Intervention;Iowa;Language;Learning;Life;life span;Longitudinal Studies;Measures;Mediating;Mental Depression;Methylation;Modeling;Modification;Mothers;neural circuit;Neuropeptides;Newborn Infant;Oranges;Outcome;Oxytocin;Oxytocin Receptor;Perinatal;Play;polygenic risk score;Pregnancy;Prevalence;Prevention strategy;prospective;prototype;Race;rare condition;receptor;Receptor Gene;recruit;repetitive behavior;Research;Research Project Grants;Resources;Rest;Risk;Risk Assessment;Risk Marker;Role;Sampling;Scanning;sex;Site;smartphone application;social;social communication;Social Development;Social Environment;Societies;Socioeconomic Status;Spottings;Stress;Testing;Time;trait;United States;Universities

PROJECT_TITLE: Project: Epigenetics, Polygenic Risk and the Social Environment in Autism


NIH_SPENDING_CATS: Genetics

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Transcription factors control the expression of genes, but much remains to be understood about how they work. The stress-response nuclear factor κB (NFκB) transcription factor family regulates cell growth, immune responses, inflammatory viral responses, and apoptotic death and is often mis-regulated in cancer, arthritis, asthma, diabetes, AIDS, and viral infections. This proposal combines rigorous theory with a wide range of biophysical experiments to characterize how active NFκB transcription complexes assemble on DNA and nucleosome arrays focusing on how NFκB selects specific genes to activate under different stress conditions in order to gain a deeper understanding of transcription activation in general.

PI_NAMEs: KOMIVES, ELIZABETH A. (contact);WOLYNES, PETER GUY

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Acceleration;Acquired Immunodeficiency Syndrome;Affinity;Apoptotic;Arthritis;Asthma;Atomic Force Microscopy;Autoimmune Diseases;Behavior;Binding;Biochemical;biological adaptation to stress;biophysical techniques;Biophysics;cell growth;Cell Nucleus;Cells;Cessation of life;ChIP-seq;Code;Collaborations;Complex;Computer Models;Coupling;Data;design;Diabetes Mellitus;Disease;DNA;DNA Binding;DNA Binding Domain;DNA Sequence;Elements;Endowment;Event;Excision;Exhibits;experimental study;Family;flexibility;Floods;Gene Expression;Genes;Genetic Enhancer Element;Genetic Transcription;Goals;Growth;I Kappa B-Alpha;Immune;Immune response;In Vitro;in vivo;Inflammatory;Invaded;Kinetics;Laboratories;Length;Malignant Neoplasms;Measures;Mediating;Micro Array Data;Molecular;molecular recognition;Monitor;Mutagenesis;mutant;Nuclear;Nuclear Export;Nuclear Proteins;Nucleosomes;Play;Process;Promoter Regions;protein complex;protein folding;Proteins;Publishing;recruit;Regulation;Relaxation;Research Personnel;response;Role;RPS3 gene;Series;simulation;single-molecule FRET;Site;Slide;Speed;stoichiometry;Stress;Structure;System;Systems Biology;Testing;theories;Therapeutic;Thermodynamics;Time;TNF gene;TNFRSF5 gene;Transactivation;Transcription Coactivator;transcription factor;Transcription Initiation;Transcriptional Activation;Transcriptional Regulation;transcriptome sequencing;Viral;Virus Diseases;Work

PROJECT_TITLE: The landscape of NFκB transcription dynamics


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Contraception/Reproduction;Networking and Information Technology R&D (NITRD);Patient Safety;Urologic Diseases;Women's Health Research

ORG_CITY: RESEARCH TRIANGLE PARK

ORG_NAME: RESEARCH TRIANGLE INSTITUTE

PHR: Project Narrative The PFDN was established in 2001 to improve the care of women with PFDs by conducting well-designed multicenter studies to inform diagnosis, prevention, and treatment. A qualified, experienced DCC is critical in helping the PFDN optimize research productivity through effective study design, implementation, data collection, quality assurance, monitoring, and statistical analysis. RTI will continue to provide multidisciplinary expertise to support high-impact collaborative clinical research studies and provide communications and logistical support to optimize the efficiency and productivity of the Network.

PI_NAMEs: GANTZ, MARIE G (contact)

PROGRAM_OFFICER_NAME: TEPEDE, ABISOLA KAFAYAT

PROJECT_TERMS: Address;Adherence;bench-to-bedside translation;Biometry;Blood;Caring;Clinical;Clinical Investigator;Clinical Research;clinical research site;Clinical Trials;Clinical Trials Data Monitoring Committees;Code;Collaborations;Communication;Communication Tools;Computer software;cost;Custom;dashboard;Data;Data Analyses;Data Collection;Data Coordinating Center;data management;data pipeline;data quality;data submission;design;Diagnosis;electronic data capture system;Emerging Technologies;Ensure;Equipment and Supplies;evidence base;experience;Fecal Incontinence;Feces;flexibility;Functional disorder;Genetic;health economics;improved;Increased frequency of micturition;innovation;Institutional Review Boards;International;Investigation;Journals;Lead;Leadership;Life;Machine Learning;Manuscripts;meetings;Methods;micturition urgency;Mission;mobile application;Monitor;Multicenter Studies;multidisciplinary;National Institute of Child Health and Human Development;Observational Study;operation;Outcome Measure;Paper;Patient Outcomes Assessments;Patients;payment;Pelvic Floor Disorders;pelvic organ prolapse;Persons;Pharmaceutical Preparations;Play;Prevention;Principal Investigator;Privatization;Procedures;Process;Productivity;protocol development;Protocols documentation;Provider;Psychometrics;Publications;Qualifying;quality assurance;remote monitoring;Reporting;repository;Research;Research Design;research study;Resources;Risk Factors;Role;Safety;Services;Site;Specimen;Speed;Statistical Data Interpretation;support network;symposium;System;Technology;Time;Time Study;tool;Training;Training Activity;translational study;Twitter;United States National Institutes of Health;Urinary Incontinence;Urine;Vagina;web platform;web portal;web site;Woman;Work

PROJECT_TITLE: Pelvic Floor Disorders Network Data Coordinating Center


ORG_CITY: Newark

ORG_NAME: UNIVERSITY OF DELAWARE

ORG_STATE: DE

PHR: Project Narrative This center of Biomedical Research Excellence is a multidisciplinary center that using synthesis, chemical biology and computation to develop molecular approaches for understanding and treating human disease, with a focus on infectious diseases and cancer.

PI_NAMEs: FOX, JOSEPH M (contact)

PROGRAM_OFFICER_NAME: BERNAL, FEDERICO

PROJECT_TERMS: Adjuvant;Analytical Chemistry;Award;Biochemistry;Biological;Biology;Capsid;catalyst;Cells;Centers of Research Excellence;Chemicals;cohort;Collaborations;Communicable Diseases;Complement;Core Facility;Custom;Delaware;demethylation;design;Disease;Engineering;Enzymes;Extramural Activities;Faculty;Faculty Recruitment;Funding;Goals;Grant;HIV;Human;Human Biology;human disease;Immune response;Infrastructure;instrumentation;interest;Kinetics;Laboratories;Legionnaires' Disease;Lung;Macromolecular Complexes;Malignant Neoplasms;Mass Spectrum Analysis;member;Mentors;Messenger RNA;Microscopy;Molecular;Molecular Target;multidisciplinary;nanoparticle;nucleotide analog;pathogenic bacteria;Pathway interactions;Phase;Pilot Projects;professor;programs;recruit;Regulation;Research;Research Personnel;Resource Sharing;screening;Services;small molecule;Structure;success;Therapeutic;tool;Tuberculosis;Universities;vaccine development;Virus

PROJECT_TITLE: Discovery of Chemical Probes and Therapeutic Leads, Phase II


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Infectious Diseases

PROJECT_TERMS: Achievement;Adjuvant;Advisory Committees;Area;Award;Biological;Biology;Biomedical Research;Capsid;career development;Career Mobility;Cells;Centers of Research Excellence;chemical synthesis;Chemicals;cohort;Communicable Diseases;Core Facility;Development;Disease;drug discovery;Educational workshop;endopeptidase Clp;Enzymes;Event;experience;Faculty;faculty mentor;flexibility;formative assessment;Funding;Goals;Grant;Group Meetings;Growth;Growth and Development function;HIV;Human;Human Biology;human disease;Immune response;Immunology;Infrastructure;Lead;Leadership;Legionnaires' Disease;Link;Lung;Macromolecular Complexes;Malignant Neoplasms;Manuscripts;Maps;meetings;member;Mentors;Messenger RNA;Microbiology;Modeling;Modification;Molecular;Molecular Probes;nanoparticle;pathogenic bacteria;Pathway interactions;Phase;Pilot Projects;Postdoctoral Fellow;Preparation;programs;Publications;recruit;Regulation;Research;research and development;Research Personnel;Research Training;Resources;Series;small molecule;Structure;Students;success;support network;Therapeutic;tool;Training;Tuberculosis;Universities;vaccine development;Virus;Vocational Guidance;Work;Writing

PROJECT_TITLE: Fox COBRE Phase II Admin Core


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Infectious Diseases

ORG_CITY: GAINESVILLE

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: NARRATIVE Chronic inflammation drives the destruction of the tissues supporting the teeth, and is the central driver of periodontal disease; however, this microbe-elicited immune response is insufficient to clear the host of periodontal pathogens such as Porphyromonas gingivalis. Our studies have recently identified the importance of sphingolipids synthesized by P. gingivalis as novel molecules capable of disrupting the host inflammatory response, and support that sphingolipid-mediated mechanisms may facilitate persistence of this organism in the host, thus providing a mechanism capable of modulation of the chronic inflammation that characterizes periodontal disease. The goal of this study is to understand precisely how P. gingivalis utilizes its sphingolipids to modulate host inflammation, with the vision toward development of novel periodontal disease treatment strategies that target these sphingolipids.

PI_NAMEs: DAVEY, MARY ELLEN;GIBSON, FRANK C (contact)

PROGRAM_OFFICER_NAME: MCNEALY, TAMARA L

PROJECT_TERMS: Affect;Atmosphere;Bacteroides;Bacteroidetes;Biochemical;bone loss;Cell Communication;Cell Culture Techniques;Cell membrane;cell motility;Cells;Chemistry;Chronic;Clinical;Collaborations;Communication;cytokine;defined contribution;Development;Disease;Elements;Gene Modified;Genes;Genetic;Genetic Transcription;Gingiva;Goals;Growth;Health;Human;Image;Immune;immune function;Immune response;Immunity;Immunologics;immunoregulation;Immunosuppression;In Vitro;in vivo;Infection;Inflammation;inflammatory milieu;Inflammatory Response;Innate Immune Response;intestinal homeostasis;Knowledge;Lipids;Macrophage;Mediating;member;Membrane;Metabolism;Methodology;Methods;Microbe;microbial;microscopic imaging;Modeling;Molecular;Mucous Membrane;Mus;mutant;Nature;neutrophil;novel;Oral;Oral cavity;Oral Examination;oral infection;oral pathogen;Organism;Pathogenesis;Pathogenicity;Periodontal Diseases;periodontopathogen;Physiology;Play;Porphyromonas gingivalis;Prevention;programs;Prokaryotic Cells;Proteins;Publications;Publishing;Research;response;Role;Signal Pathway;Signal Transduction;Signaling Molecule;Source;Sphingolipids;subgingival microbiota;Surface;symbiont;System;targeted treatment;Techniques;Testing;therapeutic development;Tissues;Tooth structure;trafficking;transcriptome sequencing;transcriptomics;treatment strategy;Vesicle;Virulence;Vision

PROJECT_TITLE: Microbial sphingolipids and suppression of host inflammation in periodontal disease


NIH_SPENDING_CATS: Bioengineering;Building Research Capacity at Institutions with Limited NIH Funding

PI_NAMEs: BAI, SHI  (contact)

PROJECT_TERMS: Address;Advisory Committees;Analytical Chemistry;Biological;Biological Process;Calorimetry;Centers of Research Excellence;Chemicals;Core Facility;cost;Custom;Delaware;Development;Doctor of Philosophy;Electronics;Face;Funding;Goals;Growth;improved;In Situ;Infrastructure;Institution;instrument;instrumentation;Kinetics;Laboratories;Leadership;Life Cycle Stages;Manufacturer;Mass Spectrum Analysis;Measures;microcalorimetry;Mission;Molecular;Monitor;NMR Spectroscopy;Nuclear Magnetic Resonance;Phase;Positioning Attribute;Proteomics;Reaction;Research;Research Personnel;Research Support;Scientist;Services;skills;Specialist;Spectrophotometry;Spectrum Analysis;Structure;Surface Plasmon Resonance;System;Technical Expertise;Therapeutic;Time;Titrations;Training;Universities;University resources;Update

PROJECT_TITLE: FOX CORE Phase II Research Core #1 Analytical


NIH_SPENDING_CATS: Chronic Pain;Dental, Oral, and Craniofacial Disease;Infectious Diseases;Neurosciences;Pain Research

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: The goal of this project is to determine the roles of trigeminal nociceptive afferents to chronic pain and alveolar bone remodeling. Positive outcomes will help to develop non-opioidergic treatment for chronic pain and to develop novel methods for better treating bone loss in periodontitis and for accelerated painless tooth movement in orthodontic treatment.

PI_NAMEs: CHUNG, MAN-KYO  (contact)

PROGRAM_OFFICER_NAME: GHIM, MELISSA M

PROJECT_TERMS: Acceleration;Address;Affect;alveolar bone;Analgesics;Area;bone loss;Bone remodeling;Brain;Brain region;career;chronic pain;chronic pain management;craniofacial;Craniofacial Pain;Dentists;Development;Goals;Homeostasis;Immune response;Infection;Injury;interest;Lead;Methods;neural;Neurobiology;Neuroimmune;Neuronal Plasticity;Neurosciences Research;Nociception;Nociceptors;novel;Oral health;orofacial;Orthodontic;Outcome;pain signal;Painless;Pathologic;Periodontal Infection;Periodontitis;programs;Research;response;Role;Scientist;Stimulus;Testing;Tissues;Tooth Movement;Tooth structure;transmission process;Trigeminal System;Visit

PROJECT_TITLE: Trigeminal nociceptors: Neural intersection of chronic pain and alveolar bone remodeling


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding

PI_NAMEs: WATSON, DONALD ALLEN (contact)

PROJECT_TERMS: Advisory Committees;Analytical Chemistry;assay development;base;Biological Process;Biomedical Research;Budgets;catalyst;Cell Culture Techniques;Centers of Research Excellence;Charge;Chemicals;Chemistry;computing resources;Core Facility;Custom;data management;Delaware;Development;Doctor of Philosophy;Electronics;Engineering;Equipment;experience;Faculty;Future;Goals;Growth;Industrialization;Infrastructure;instrument;instrumentation;Intellectual Property;Laboratories;Libraries;Maintenance;Microscopy;Mission;Modeling;Molecular;Phase;Policies;Publications;Reaction;recruit;Reporting;Research;Research Personnel;Resource Sharing;Schedule;Scientist;Services;small molecule;Specialist;Synthesis Chemistry;Therapeutic

PROJECT_TITLE: FOX CORE Phase II Research Core #1 Synthesis


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Tuberculosis

ORG_DEPT: PHARMACOLOGY

PHR: Project Narrative Tuberculosis (TB) presents an ongoing global challenge to medical science that will only be met by multiple approaches. Due to the length of even “routine” TB therapy and the age of existing drugs – which contributes to the emergence of devastating resistant forms of the disease – the discovery of new drugs, especially those that function by new mechanisms of action, has become critical. In this work, we seek to discovery novel TB therapeutics that act at a newly discovered biochemical target essential to the infective organism called PptT.

PI_NAMEs: AUBE, JEFFREY  (contact)

PROGRAM_OFFICER_NAME: BOYCE, JIM P

PROJECT_TERMS: Age;Anabolism;analog;Antimycobacterial Agents;Antitubercular Agents;Back;Binding;Biochemical;Biological Assay;Cardiotoxicity;Carrier Proteins;Chemicals;Client;Clinic;Clinical;Collaborations;Critiques;design;Disease;drug candidate;Drug Kinetics;Drug resistance;drug-sensitive;extensive drug resistance;Fatty Acids;Goals;Growth;Health Personnel;high throughput screening;in silico;In Vitro;in vivo;inhibitor;knock-down;Knock-out;Laboratories;Lead;Length;Macrophage;Mammalian Cell;Measurement;Mediating;Medical;Medicine;Metabolic;metabolomics;Microsomes;Modeling;Mus;mycobacterial;Mycobacterium tuberculosis;novel;novel therapeutics;Organism;Orthologous Gene;Persons;Pharmaceutical Preparations;phosphopantetheinyl transferase;physical property;pre-clinical;preclinical development;programs;Property;Protocols documentation;rational design;Reporting;Resistance;Resolution;response;Rifampin;Safety;scaffold;Science;Series;Sodium Channel;Structure;Structure-Activity Relationship;synergism;Therapeutic;Therapeutic Agents;Treatment Protocols;Tuberculosis;tuberculosis drugs;tuberculosis treatment;Variant;Virulence Factors;Work;X-Ray Crystallography

PROJECT_TITLE: Discovery of Phospopantetheinyl Transferse Inhibitors Against Mycobacterium tuberculosis

STUDY_SECTION: DDR

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


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases

PI_NAMEs: NEUNUEBEL, MARIA RAMONA (contact)

PROJECT_TERMS: Acceleration;Address;Affinity;Amino Acids;Antibiotics;Bacteria;Bacterial Proteins;Binding;Binding Proteins;Biology;Cell membrane;Cells;Chemicals;Collaborations;combat;Complex;Confocal Microscopy;Copper;Critical Pathways;Crystallization;Cyclooctenes;Cytosol;Disease;drinking water;efflux pump;Endoplasmic Reticulum;Ensure;Face;fluorophore;Foundations;Genetic Diseases;Goals;Golgi Apparatus;Gram-Negative Bacteria;Head;Human;Immune;Immunity;improved;Individual;Infection;Inositol;insight;Intervention;Knowledge;Label;Legionella;Legionella pneumophila;Legionnaires' Disease;Ligands;Lipid Binding;Lipids;Lung;Lysosomes;Macrophage;Maps;Mediating;Membrane;Membrane Protein Traffic;Modeling;Molecular;Molecular Target;Mutation Analysis;myoinositol;novel;Organelles;Outcome;pathogen;pathogenic bacteria;Pathway interactions;permissiveness;Persons;Phase;Phosphatidylinositols;Phosphorylation;Plasma Cells;Pneumonia;Positioning Attribute;prevent;protein complex;Proteins;public drinking;Public Health;Reaction;recruit;Research;Site;spatiotemporal;Specificity;Surface Plasmon Resonance;System;Testing;Therapeutic;Time;trafficking;Transmembrane Transport;Transport Process;Travel;Vacuole;Vesicle;Virulence;Work;X-Ray Crystallography

PROJECT_TITLE: Molecular mechanisms supporting bacterial survival within immune cells


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Diabetes;Emerging Infectious Diseases;Infectious Diseases;Wound Healing and Care

ORG_DEPT: DERMATOLOGY

PHR: PROJECT NARRATIVE: This project aims to elucidate a novel pathway in early neutrophil recruitment that appears critical to host defense against skin and soft tissue infections. It addresses the decreasing ability of our antibiotic armamentarium to treat increasingly resistant microbes, a global health crisis that is driving a need to develop anti-infective therapies that augment the host immune response. This work is relevant to public health as it will provide new targets for the development of alternative antimicrobial therapies utilizing innate host defense mechanisms, which are currently lacking.

PI_NAMEs: DORSCHNER, ROBERT A (contact)

PROGRAM_OFFICER_NAME: UNDALE, ANITA H

PROJECT_TERMS: Address;Adhesions;Alternative Therapies;Anti-Infective Agents;anti-microbial peptide;Antibiotic Resistance;Antibiotics;antimicrobial;Automobile Driving;Biological Assay;Biology;Biometry;Bone Marrow Examination;career;career development;CD44 gene;Cells;Cellular biology;Clinical;Clinical Research;clinical training;Communities;Cutaneous;cytokine;Data;Dermatology;design;Development;Diabetes Mellitus;diabetic;diabetic patient;Disease;Doctor of Philosophy;Elements;Environment;experience;Face;Failure;fighting;Functional disorder;Funding;Generations;global health;Goals;Grant;Hospitals;Host Defense;Host Defense Mechanism;Human;human model;Hyaluronic Acid;Immune;Immune response;Immunity;Immunophenotyping;Immunotherapy;Impairment;in vivo;Individual;Infection;Infectious Skin Diseases;Inflammation;Inflammatory Response;innovation;Knockout Mice;Knowledge;Lesion;Leukocytes;Mediating;Membrane Proteins;Mentors;methicillin resistant Staphylococcus aureus;Microbe;Microbial Antibiotic Resistance;migration;Modeling;Molecular Biology;Morbidity - disease rate;mortality;mouse model;Mus;Neutropenia;neutrophil;Neutrophil Activation;Neutrophil Infiltration;novel;Operative Surgical Procedures;pathogen;Pathway interactions;Positioning Attribute;Prevalence;Production;programs;Public Health;recruit;Regulation;Research;Research Personnel;Research Training;Resistance;Respiratory Burst;response;Risk;Role;Scientist;Sepsis;Signal Transduction;Skin;Skin injury;Skin Tissue;Soft Tissue Infections;Soft Tissue Injuries;Staphylococcus aureus infection;Surgical Wound Infection;Systemic disease;targeted treatment;Technical Expertise;Techniques;Testing;therapeutic target;therapy development;Traction;trafficking;Training;Translating;Work;wound healing;Writing

PROJECT_TITLE: The role of the ECRG4 in Host Defense of Staph Aureus Infection

STUDY_SECTION: AMS

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Special Grants Study Section[AMS]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Building Research Capacity at Institutions with Limited NIH Funding;Emerging Infectious Diseases;Infectious Diseases;Orphan Drug;Rare Diseases;Tuberculosis

PI_NAMEs: SCHMITZ, KARL ROBERT (contact)

PROJECT_TERMS: Address;Affinity;Anti-Bacterial Agents;Aromatic Compounds;Automobile Driving;Bacteria;Binding;Biochemical;Biochemistry;Biological;Biological Assay;Biology;biophysical techniques;Cells;Cessation of life;Characteristics;Chemicals;Clinical;Collaborations;combat;Complex;Cytosol;Development;Dissection;Drug resistance;Drug resistance in tuberculosis;Drug resistant Mycobacteria Tuberculosis;endopeptidase Clp;Enzymes;Epidemic;Family;Fluorescence Resonance Energy Transfer;Genus Mycobacterium;Growth;Homologous Gene;Human;improved;In Vitro;Infection;Kinetics;Label;Lead;Libraries;Medical;Mitochondria;Modeling;Modernization;Multidrug-Resistant Tuberculosis;mycobacterial;Mycobacterium tuberculosis;novel;Pathway interactions;Peptide Hydrolases;pharmacologic;Phase;Physiology;Population;protein folding;Public Health;Regulation;Reporting;scaffold;small molecule;Specificity;Synthesis Chemistry;System;targeted treatment;Therapeutic;therapeutic development;therapeutic enzyme;therapeutic target;Tuberculosis;Work;World Health Organization

PROJECT_TITLE: Dissection of Mycobacterium tuberculosis Clp protease assembly, activity and regulation


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Electronic Nicotine Delivery Systems;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pediatric;Prevention;Substance Misuse;Telehealth;Tobacco;Tobacco Smoke and Health

PHR: Project Narrative The use of vaping products (i.e., e-cigarettes), has risen exponentially in the past decade, especially among teens and young adults. This proposal aims to use social media to detect individuals socially networking about vaping and to connect these users with a digital intervention system (i.e., chatbot with mobile app) to increase their risk awareness and support vaping cessation. Such an integrated system has the potential to improve public health outcomes related to vaping and to inform the feasibility of such a chatbot tool to sustain mHealth intervention engagement.

PI_NAMEs: CAVAZOS-REHG, PATRICIA A (contact)

PROGRAM_OFFICER_NAME: AKLIN, WILL

PROJECT_TERMS: acceptability and feasibility;Acute;Adolescent and Young Adult;Age;Artificial Intelligence;Attitude;Awareness;Behavior;Cessation of life;chatbot;Chronic;Cigarette;Clinical;combustible cigarette;Control Groups;Data;deep learning;design;Detection;detection platform;digital applications;digital intervention;digital tool;digital treatment;Electronic cigarette;Electronic Nicotine Delivery Systems;Eligibility Determination;eligible participant;Ensure;evidence base;experience;feasibility testing;Generations;Health;Health Personnel;improved;improved outcome;Individual;interest;Intervention;Long-Term Effects;Lung infections;lung injury;Machine Learning;mhealth interventions;Mining;mobile application;Modeling;Motivation;Natural Language Processing;Outcome;outreach;Parents;Participant;Perception;Population;Populations at Risk;primary outcome;Public Health;Randomized;Randomized, Controlled Trials;recruit;Reporting;respiratory;Risk;risk perception;Sampling;secondary outcome;Smoker;Smoking;social media;Social Network;Source;Specificity;support tools;Surveys;System;Systems Integration;Techniques;Technology;Teenagers;Testing;Time;tobacco advertising;Tobacco use;tool;Twitter;usability;vaping;Waiting Lists;young adult;Youth

PROJECT_TITLE: Testing the feasibility and acceptability of social media and digital therapeutics to decrease vaping behaviors

STUDY_SECTION: CIDH

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


ORG_DEPT: PATHOLOGY

PHR: Project Narrative Combination antiretroviral therapy results in the elimination of nearly all actively HIV infected cells. However, the small reservoir of remaining cells causes substantial morbidity due to chronic inflammation that has been linked to defects in the intestinal barrier. A better understanding of the fundamental causes of inflammation in HIV infected people will lead to the development of new therapies that will alleviate chronic inflammation and improve the health of PLWH.

PI_NAMEs: COLLINS, KATHLEEN L.;PARKOS, CHARLES A (contact)

PROGRAM_OFFICER_NAME: NGUYEN, KHOA DINH DANG

PROJECT_TERMS: Address;antiretroviral therapy;Area;Biology;bone;Cardiovascular Diseases;CD4 Positive T Lymphocytes;Cell Line;Cell Physiology;Cells;Chronic;Collaborations;comorbidity;cytokine;Data;Defect;Development;Epithelial Cells;Epithelium;experimental study;Exposure to;Functional disorder;Funding;Gastrointestinal tract structure;Goals;gut inflammation;Health;HIV;HIV Infections;HIV-1;HIV/AIDS;Homeostasis;Human;Immune;immune activation;Impairment;improved;Individual;Infection;Inflammation;Inflammatory;insight;Interleukin-1 beta;Interleukin-6;intestinal barrier;intestinal epithelium;Intestines;Lamina Propria;Lead;Link;Metabolic syndrome;Methodology;microbial;Molecular;Morbidity - disease rate;mortality;nef Protein;neurocognitive disorder;novel therapeutics;Pathway interactions;Permeability;Persons;premature;Prevention;Process;Production;Research;Research Personnel;response;Signal Transduction;Source;synergism;T-Lymphocyte;Testing;therapeutic target;TNF gene;trafficking

PROJECT_TITLE: Molecular mechanisms underlying HIV related intestinal epithelial barrier dysfunction

STUDY_SECTION: HCCS

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Lung;Pulmonary Hypertension;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE The proposed research is relevant to public health: it will determine the underlying mechanisms of how the secreted peptide apelin prevents right heart failure in pulmonary hypertension, a progressive and incurable disease characterized by excessive pulmonary vasoconstriction, pulmonary remodeling, right heart failure and death. Right heart function determines survival in pulmonary hypertension; however, we don’t understand what causes right heart failure and if it can be reversed. The proposed work is relevant to the mission of the NHLBI, it will lead to the development of novel right heart-directed therapies for patients with pulmonary hypertension and cardiopulmonary disease.

PI_NAMEs: FRUMP, ANDREA LEE (contact)

PROGRAM_OFFICER_NAME: SUTLIFF, ROY L

PROJECT_TERMS: ACE2;Agonist;angiogenesis;Angiotensin-Converting Enzyme Inhibitors;APLN gene;Blood Vessels;Cardiac;Cardiac Myocytes;Cells;Cessation of life;Clinical;Data;Development;Disease;Drug Delivery Systems;Endothelial Cells;Experimental Models;Functional disorder;Goals;Heart;heart function;Human;human induced pluripotent stem cells;Impairment;improved;in vivo;induced pluripotent stem cell;Industry;interest;Link;Lung;Mediating;Mediator;Mission;Modeling;Molecular;mortality;National Heart, Lung, and Blood Institute;novel;Nuclear;Nuclear Receptors;Oral;Outcome;Pathway interactions;Patient Rights;Patients;Peptides;Peptidyl-Dipeptidase A;prevent;protective effect;Public Health;Publishing;pulmonary artery endothelial cell;Pulmonary artery structure;Pulmonary Heart Disease;Pulmonary Hypertension;pulmonary vascular remodeling;Pulmonary Vascular Resistance;pulmonary vasoconstriction;receptor;receptor-mediated signaling;Renin-Angiotensin-Aldosterone System;Research;right ventricular failure;Right Ventricular Function;right ventricular remodeling;Rodent Model;Role;Signal Pathway;Signal Transduction;targeted treatment;Testing;Therapeutically Targetable;Tissues;treatment strategy;Vasodilation;Ventricular;Work

PROJECT_TITLE: The emerging role of apelin, RAAS, and ACE2 crosstalk in pulmonary hypertension

STUDY_SECTION: RIBT

STUDY_SECTION_NAME: Respiratory Integrative Biology and Translational Research Study Section[RIBT]


ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE The discovery of RNA enzymes, including natural self-cleaving nucleolytic ribozymes, has stimulated and invigorated curiosity in the chemical principles underlying the origin of life, leading to the formulation of the RNA world hypothesis. The proposed structure-function studies of precatalytic, vanadate transition state mimic and product states of the recently identified hovlinc ribozyme, as well as proposed comprehensive studies at clarifying existing discrepancies associated with structure-guided mechanistic understanding of twister (Twr) and twister-sister (TSr) ribozyme cleavage chemistry, will enhance our mechanistic understanding of the catalytic versatility of RNA and elucidate the underlying topological and catalytic principles impacting on gene regulation, genomic integrity and prebiotic RNA world events.

PI_NAMEs: PATEL, DINSHAW J (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: 3-Dimensional;Acids;Active Sites;Address;analog;Architecture;base;Binding;Binding Sites;Biochemical;Biogenesis;Biological;Catalysis;Catalytic RNA;Cations;Chemicals;Chemistry;Collaborations;comparative;Conserved Sequence;Crystallization;Curiosities;Dependence;Divalent Cations;Elements;Enzymes;Event;Evolution;follow-up;Formulation;functional group;Gene Expression Regulation;Genes;genome integrity;genome wide screen;Genomics;Goals;Hepatitis Delta Virus;Human;Hydration status;Hydrogen Bonding;Hydrophobic Interactions;inorganic phosphate;insight;interest;Introns;Life;Ligation;Literature;macromolecule;Measurement;Measures;Mediating;Messenger RNA;Modification;Molecular Conformation;Monitor;mutant;Oxygen;Peptides;Peptidyltransferase;phosphodiester;Play;Positioning Attribute;prebiotics;protonation;Publishing;Reporting;Ribosomes;RNA;RNA Processing;RNA Splicing;RNase P;Role;Screening Result;Sister;Site;Specificity;Spliceosomes;Structure;Structure-Activity Relationship;Temperature;Time;Untranslated Regions;Untranslated RNA;Vanadates;varkud satellite ribozyme;Vertebral column;Visit

PROJECT_TITLE: Structure-Activity Based Mechanistic Insights into Cleavage Chemistry by Self-Cleaving Nucleolytic Ribozymes

STUDY_SECTION: MSFA

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