NIH_SPENDING_CATS: Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Mental Illness;Neurosciences;Orphan Drug;Pediatric;Rare Diseases;Rett Syndrome;Women's Health Research

PHR: PROJECT NARRATIVE Patients with primary GRM7 mutations and mice lacking metabotropic glutamate receptor 7 (mGlu7) share many phenotypes characteristic of the monogenetic disorder, Rett syndrome (RTT), and we have identified dramatic reductions in mGlu7 expression in brain samples from patients diagnosed with RTT. Our data indicate that compounds that potentiate mGlu7 activity reverse many abnormal RTT phenotypes; coupled with the single gene nature of RTT, this suggests that pairing mGlu7 potentiation with RTT treatment may represent a viable clinical path. We propose to conduct a chemical optimization campaign to develop a candidate for eventual clinical testing, define the RTT populations most likely to respond effectively and safely to this treatment, and validate an EEG biomarker with clinical translatability.

PI_NAMEs: LINDSLEY, CRAIG ;NISWENDER, COLLEEN M (contact)

PROGRAM_OFFICER_NAME: MANDELBLAT-CERF, YAEL

PROJECT_TERMS: Agreement;Alleles;Amygdaloid structure;Anxiety;Apnea;Architecture;Attention deficit hyperactivity disorder;autism spectrum disorder;autism symptoms;Biological Markers;Brain;Brain region;Characteristics;Chemicals;Chemosensitization;Clinic;Clinical;clinical development;clinical diagnosis;clinical heterogeneity;Clinical Pathways;clinical translation;Cognitive;Cognitive deficits;cohort;common symptom;comparison control;Coupled;Data;Development;Diagnosis;Disease;DNA Sequence Alteration;Dose;drug development;Drug Kinetics;Drug Targeting;drug-like compound;efficacy testing;Electroencephalography;Engineering;epigenetic regulation;Epilepsy;Exhibits;Expression Profiling;Frequencies;Future;G-Protein-Coupled Receptors;gamma-Aminobutyric Acid;Genes;Genetic Diseases;Glutamates;Goals;Hippocampus;Human;in vivo;Intellectual functioning disability;Investigational Drugs;Knock-out;Knockout Mice;Link;Location;Long-Term Potentiation;loss of function mutation;Mental Depression;Mental disorders;Metabolism;metabotropic glutamate receptor 7;Metabotropic Glutamate Receptors;Methyl-CpG-Binding Protein 2;Modeling;Motor;mouse model;Mus;mutant;mutant mouse model;Mutation;Nature;Nervous System Disorder;Neurodevelopmental Disorder;Neurologic;neurotransmitter release;novel therapeutic intervention;Outcome Measure;Pathogenicity;patient subsets;Patients;Pattern;Pharmaceutical Chemistry;Pharmacology;Phenotype;Point Mutation;Population;positive allosteric modulator;pre-clinical;Pre-Clinical Model;presynaptic;programs;Proteins;receptor;REM Sleep;Reporting;research clinical testing;respiratory;response;Rett Syndrome;Rodent;Role;Safety;Sampling;scaffold;Schizophrenia;Seizures;Single Nucleotide Polymorphism;Sleep;sleep abnormalities;small molecule;social;Stereotyped Behavior;stereotypy;Synaptic plasticity;Syndrome;targeted treatment;Testing;Therapeutic;Tissues;tool;Transcriptional Regulation;Treatment Efficacy;Validation

PROJECT_TITLE: Development of mGlu7 receptor allosteric modulators for neurological and psychiatric disorders

STUDY_SECTION: DDNS

STUDY_SECTION_NAME: Drug Discovery for the Nervous System Study Section[DDNS-R]


ADMINISTERING_IC: GM

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

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

ORG_CITY: FARMINGTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PI_NAMEs: HOCH, JEFFREY C (contact)

PROJECT_TERMS: Archives;Bayesian Analysis;Biomolecular Nuclear Magnetic Resonance;clinical application;Cloud Computing;cluster computing;Collaborations;Communities;community empowerment;Complex;computational platform;Computer software;computerized data processing;computing resources;Custom;dashboard;Data;Data Analyses;Data Storage and Retrieval;Dedications;Deposition;Development;Ecosystem;Educational workshop;Emerging Technologies;empowerment;Encapsulated;Environment;Fostering;Goals;Grant;Health Insurance Portability and Accountability Act;improved;Infrastructure;Institution;Licensing;Link;meetings;Metadata;novel;Occupations;portability;programs;Protocols documentation;Publishing;Reporting;repository;Reproducibility;Research Personnel;Resources;Running;Services;Side;Technology;Time;tool;Training;Universities;Update;virtual;virtual machine;web server;web services

PROJECT_TITLE: NMRbox Platform

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-T]


PROJECT_TERMS: analytical tool;Biomolecular Nuclear Magnetic Resonance;Chemicals;cluster computing;Collection;Communities;Complex;Computer software;computerized data processing;Consumption;Custom;Data;Data Analyses;data dictionary;data modeling;data repository;Data Set;data submission;data visualization;Deposition;design;Development;Ensure;Environment;experimental study;Extensible Markup Language;file format;Fostering;Glean;Goals;Harvest;improved;Individual;Information Management;interoperability;Investigation;Knowledge;Libraries;Manuals;metabolomics;Metadata;Occupations;open source;Operating System;Pathway interactions;preservation;Process;Productivity;prototype;public database;Pythons;reconstruction;Recording of previous events;Reporting;repository;Reproducibility;Research;Research Personnel;Resources;Sampling;Services;small molecule;Software Tools;System;Time;tool;Translations;Validation;Work

PROJECT_TITLE: NMRbox information management: CONNJUR and BMRB integration


PI_NAMEs: EGHBALNIA, HAMID R (contact)

PROJECT_TERMS: Address;Advanced Development;analytical method;Area;Automation;Bayes Theorem;Bayesian Analysis;Bayesian Method;Biological;Biomolecular Nuclear Magnetic Resonance;Cells;Collaborations;Communication;Communities;community engagement;Complement;computational platform;Computer Analysis;computer framework;Computer software;computerized data processing;Computing Methodologies;Data;Data Analyses;Data Analytics;data exchange;data format;data modeling;Deposition;design;Development;Diagnostic;Ecosystem;Ensure;Evaluation;Experimental Models;flexibility;Future;Goals;Health Status;heterogenous data;Hour;improved;instrument;Investigation;Knowledge;Lead;Libraries;Location;Mass Spectrum Analysis;mathematical methods;Metabolic;metabolomics;Modeling;Molecular;Molecular Profiling;NMR Spectroscopy;Pharmaceutical Preparations;preservation;Probability;Procedures;Process;Proteins;Relaxation;Reliability of Results;Reproducibility;Research Personnel;Resource Development;Resources;Sampling;Science;Shapes;signature molecule;small molecule;Source;Specific qualifier value;Statistical Models;support tools;Technology;Technology Assessment;tool;Translations;Validation;virtual machine;Visual;Visualization software;Work

PROJECT_TITLE: NMRbox: Bayesian Analytics


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Human Genome;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: CHICAGO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Narrative Oral cavity squamous cell carcinoma (OCSCC), the most common subtype of head and neck squamous cell carcinoma (HNSCC), is a devastating disease with poor overall survival and limited targeted therapeutic options. While our preliminary data provide strong evidence that PDCD10 (a multifaceted protein shown to promote a range of oncogenic cellular processes in several solid malignancies) may play a role in driving OCSCC evolution, the direct relevance of PDCD10 in regulating head and neck tumorigenesis have not yet been studied. This proposal will use in vivo and organoid based preclinical models, coupled with comprehensive bioinformatics analysis of longitudinally collected primary human specimens, to evaluate the role of PDCD10 in HNSCC cancerogenesis and driving aggressive tumor cells behavior.

PI_NAMEs: IZUMCHENKO, EVGENY (EUGENE) G (contact);SHEN, LE

PROGRAM_OFFICER_NAME: CHEN, ZHONG

PROJECT_TERMS: Alcohol consumption;Animals;anti-cancer;anti-tumor immune response;Apoptosis;Automobile Driving;beta catenin;Bioinformatics;Biological Markers;Biology;cancer stem cell;carcinogenesis;Carcinogens;cell behavior;Cell Maintenance;Cell Physiology;Cell Proliferation;Cessation of life;Chemoresistance;cohort;Coupled;Data;Data Set;design;Detection;Development;Diagnosis;Disease;drinking water;Dysplasia;effective therapy;Endowment;Epithelium;Event;Evolution;Exposure to;Genes;Genomics;Head and Neck Squamous Cell Carcinoma;Head and neck structure;Histologic;Histopathologic Grade;HPV negative;Human;Human Characteristics;Human papilloma virus infection;Hyperkeratosis;improved;in vivo;Incidence;inhibitor;insight;interest;Knock-out;Knowledge;Lesion;Link;longitudinal analysis;longitudinal dataset;LoxP-flanked allele;Malignant - descriptor;Malignant Breast Neoplasm;malignant mouth neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;malignant oropharynx neoplasm;Mediating;Mesenchymal;Modeling;Molecular;Morbidity - disease rate;Morphology;mortality;mouse model;mouth squamous cell carcinoma;Mucous Membrane;Mus;neoplastic;neoplastic cell;new therapeutic target;novel;novel strategies;Oncogenes;Oncogenic;Oral;Oral Stage;oral tumorigenesis;organizational structure;Organoids;overexpression;Pathway interactions;patient prognosis;Patients;Pattern;Persons;Phenotype;Physiology;Play;pre-clinical;Pre-Clinical Model;Prevalence;Prognosis;Prognostic Marker;Proteins;Protocols documentation;Quality Control;Regulation;Reporting;Risk;Risk Assessment;Role;Sampling;self organization;self-renewal;Signal Pathway;Signal Transduction;Site;Small Intestines;Solid;Specimen;Squamous Epithelium;stem cell function;stem cell population;stem cell self renewal;stem cell survival;stem cell therapy;stem cells;stemness;Tamoxifen;targeted treatment;Therapeutic;Therapeutic Intervention;therapeutic target;tobacco products;Tongue;tool;transcriptome sequencing;transcriptomics;tumor;tumor progression;Tumor Promotion;tumorigenesis;Up-Regulation;Wild Type Mouse

PROJECT_TITLE: PDCD10 as a novel driver for head and neck squamous cell carcinoma development

STUDY_SECTION: BCO

STUDY_SECTION_NAME: Biochemical and Cellular Oncogenesis Study Section[BCO]


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

PROJECT_TERMS: Acceleration;Address;analytical method;Archives;Automation;Automobile Driving;Bayesian Analysis;Biological;Biomolecular Nuclear Magnetic Resonance;Clinical;Communities;Complement;Complex;computational platform;computer infrastructure;Computer software;computerized data processing;Computers;computing resources;Data;Data Analyses;data management;data reduction;drug discovery;Drug Screening;Ensure;Environment;Face;Frequencies;Funding;Goals;Health protection;improved;innovation;Membrane;metabolomics;mimetics;Molecular;Molecular Structure;Names;novel;Performance;Proteins;Relaxation;Reproducibility;Research;Research Personnel;Resolution;Running;Selection Criteria;Services;small molecule;solid state;Source;structural biology;technology development;Testing;Time;tool;Translations

PROJECT_TITLE: Driving Biomedical Projects


PROJECT_TERMS: Adopted;Asia;Biomedical Research;Biomolecular Nuclear Magnetic Resonance;Cloud Computing;Code;Collaborations;commercialization;Communities;Community Developments;community engagement;Computer software;computerized data processing;computing resources;Data;Data Analyses;data dictionary;data modeling;Development;Documentation;Educational workshop;Ensure;Exposure to;Extensible Markup Language;Fostering;Future;Goals;Hand;Human;Infrastructure;Institution;Instruction;Metadata;Methodology;migration;novel;open source;Participant;programs;public repository;repository;Reproducibility;Research;Research Personnel;Resources;Services;Software Tools;Source Code;Stream;sustainable resource;Technology;technology development;technology training;tool;Training;virtual delivery;virtual machine;web site

PROJECT_TITLE: Community Engagement


ADMINISTERING_IC: AI

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: MADISON

ORG_NAME: FLUGEN, INC.

ORG_STATE: WI

PHR: Respiratory infections with influenza viruses cause severe morbidity and mortality in humans and animals worldwide. Yet, current influenza vaccines offer suboptimal protection even when matched to the circulating strain. Flu vaccines that provide broad-spectrum protection against matched and mismatched strains are urgently needed. In this proposal, we will further develop our prototype monovalent M2SR vaccine as a quadrivalent broadly-protective influenza vaccine that can provide effective protection against drifted influenza viruses.

PI_NAMEs: BILSEL, PAMUK  (contact)

PROGRAM_OFFICER_NAME: GORDON, JENNIFER L

PROJECT_TERMS: Acceleration;Address;Adult;Advanced Development;aged;analytical method;Animal Model;Animals;Antibodies;Antibody titer measurement;Australia;Biological Assay;Birds;Category C pathogen;cell bank;Cell Line;Cells;Cessation of life;Clinical Research;Clinical Trials;cross immunity;cross reactivity;Development;Distant;DNA;egg;Elderly;Evaluation;experimental study;Ferrets;flasks;flu;Growth;Health;Hemagglutinin;Hospitalization;Human;human old age (65+);Immune response;Immunity;immunogenicity;Inactivated Vaccines;Individual;Influenza;Influenza A virus;Influenza A Virus, H1N1 Subtype;Influenza A Virus, H3N2 Subtype;Influenza A Virus, H5N1 Subtype;Influenza B Virus;influenza virus strain;influenza virus vaccine;influenzavirus;manufacture;manufacturing process;Morbidity - disease rate;mortality;Mucous Membrane;multidisciplinary;Mutation;National Institute of Allergy and Infectious Disease;National Security;neutralizing antibody;novel;pandemic influenza;pandemic virus;Pathogenicity;Population;Process;Production;Proteins;prototype;Public Health;Qualifying;Reagent;Recommendation;Records;Reporting;research clinical testing;Residual state;Respiratory Disease;Respiratory Tract Infections;Running;Safety;seasonal influenza;Seasons;seropositive;Serum;Specific qualifier value;T cell response;Testing;Training;universal influenza vaccine;Update;Vaccination;vaccine access;Vaccine Antigen;vaccine effectiveness;vaccine efficacy;vaccine immunogenicity;Vaccine Production;Vaccines;Vial device;virtual;Virus

PROJECT_TITLE: IND-enabling studies of an intranasal, single-replication M2SR influenza vaccine


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Skin Cancer

ORG_CITY: SALT LAKE CITY

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Melanoma is a common and highly lethal cancer. ARF6 is a protein that promotes growth, invasion and metastasis of melanoma and other cancers. Our experiments will impact cancer research by determining how ARF6 controls very common cancer pathways and by providing pre-clinical testing of ARF6-targeted therapy in multiple complementary models of melanoma.

PI_NAMEs: GROSSMANN, ALLIE H. (contact)

PROGRAM_OFFICER_NAME: BENAVIDEZ, JUSTIN MICHAEL

PROJECT_TERMS: Acceleration;ADP-ribosylation factor 6;Adult;Affect;Aftercare;Anoikis;anti-cancer research;Apoptosis;Apoptotic;Biological Assay;Biological Markers;BRAF gene;burden of illness;cancer type;Cell Line;Cell Physiology;Cell Proliferation;Cell Survival;Child;Clinical;cohort;Combined Modality Therapy;CRISPR/Cas technology;Cutaneous Melanoma;Data;Disease;Disease Progression;Drug resistance;efficacy testing;Elderly;Engineering;experimental study;Genes;Genetic;Goals;Growth;Growth and Development function;Human;Impairment;improved;In Situ Nick-End Labeling;In Vitro;in vivo;Incidence;inhibitor;insight;Invaded;Link;Maintenance;Malignant Neoplasms;MAP Kinase Gene;Measures;Mediating;MEK inhibition;MEKs;melanocyte;Melanoma;Melanoma Cell;Melanoma patient;Metastatic Melanoma;middle age;Mitosis;Modeling;Molecular;Monomeric GTP-Binding Proteins;mouse model;Mus;mutant;Mutation;Neoplasm Metastasis;neoplastic cell;novel;novel therapeutics;Nuclear;Oncogenic;Pathway interactions;patient derived xenograft model;Patients;pharmacologic;PI3K/AKT;PIK3CG gene;Positioning Attribute;Preclinical Testing;Primary Neoplasm;Proliferating;protein transport;Proteins;Proteomics;Publishing;RAS driven cancer;ras Proteins;Recurrence;Regulation;Reporting;Resistance;response;Role;Safety;Serum;Signal Transduction;Signaling Protein;Specificity;Stains;standard of care;success;targeted treatment;Testing;Therapeutic Intervention;therapeutic target;trafficking;transcriptome;Treatment Efficacy;Treatment outcome;tumor;tumor DNA;tumor growth;tumor initiation;tumor progression;Withdrawal;young adult

PROJECT_TITLE: Targeting Rheostatic Mechanisms of Melanoma Progression

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: STORRS-MANSFIELD

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

PHR: Project Narrative Satellite cells are responsible for the marked regenerative capacity of skeletal muscle. Although these stem cells were discovered more than 50 years ago, the molecular mechanisms that program satellite cells for muscle differentiation are incompletely understood. Using unique mouse lines and strategies, the proposed studies will determine the functions of two key myogenic regulatory proteins (MyoD and Myf5) in satellite cell development, myogenic programming and differentiation.

PI_NAMEs: GOLDHAMER, DAVID J (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: Address;Adopted;Adult;Alleles;Anatomy;Bioinformatics;Biological Assay;Candidate Disease Gene;candidate identification;Cell Lineage;Cell Physiology;Cell Therapy;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;conditional knockout;CRISPR/Cas technology;Data;Defect;Degenerative Disorder;Development;Differentiation and Growth;Distal;DNA;dosage;Elements;Embryo;embryo cell;Embryonic Development;Enhancers;Environment;Exhibits;experimental study;fetal;Fiber;Gene Targeting;Genes;Genetic;Genetic Enhancer Element;Genetic Recombination;genetic regulatory protein;Genetic Transcription;genome-wide;Heterogeneity;Immunofluorescence Immunologic;in vivo;injured;Injury;insight;Knock-out;Mediating;Messenger RNA;Methodology;MicroRNAs;Molecular;Mus;Muscle;muscle regeneration;Muscle satellite cell;Mutagenesis;mutant;Myoblasts;MyoD Protein;Myogenic Regulatory Factors;Natural regeneration;Neonatal;novel;Nucleic Acid Regulatory Sequences;Pathway interactions;Phenotype;Polymerase;Population;Positioning Attribute;Precision Run-On Sequencing;prenatal;programs;promoter;Property;Proteins;Publishing;Regenerative capacity;Regulation;Regulatory Element;Regulatory Pathway;Reporter Genes;Research;response;Running;self-renewal;single-cell RNA sequencing;Skeletal Muscle;skeletal muscle growth;Skeletal muscle injury;stem cell function;stem cells;Testing;tibialis anterior muscle;Tissues;tool;Transcriptional Regulation;transcriptome;transcriptome sequencing;Transfection;Transgenic Mice;Transgenic Organisms

PROJECT_TITLE: Regulation of Satellite Cell Development, Programming and Differentiation by Myogenic Factors

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]


ADMINISTERING_IC: HL

ED_INST_TYPE: HOSPITALS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cancer;Clinical Research;Digestive Diseases;Hematology;Immunotherapy;Lymphatic Research;Lymphoma;Microbiome;Nutrition;Orphan Drug;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: PROJECT NARRATIVE  For many patients with blood cancers, undergoing allogeneic bone marrow transplantation is the only chance for cure, but comes with a serious risk for developing inflammation of the intestines that can be life- threatening. In this application, we propose exploring strategies in these patients to protect the mucus layer in the large intestine, which plays a key role in separating the lining of the intestine from the bacteria that reside within the intestine.

PI_NAMEs: JENQ, ROBERT  (contact)

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: Acute;Acute Graft Versus Host Disease;Acute leukemia;Allogeneic Bone Marrow Transplantation;Allogenic;Antibiotics;Azithromycin;Bacteria;Biological Assay;Biometry;Carbapenems;Cells;chemotherapy;Chronic Leukemia;Clinical;clinical translation;Colon;commensal bacteria;conditioning;Consumption;Coupled;Data;Development;Diet Monitoring;dietary;Dietary intake;dietary restriction;Evaluation;experimental study;Feces;Fermentation;Fever;Functional disorder;Gene Expression;Gnotobiotic;graft vs host disease;gut inflammation;gut microbiome;Hematologic Neoplasms;Hematological Disease;Hematopoietic Neoplasms;Hematopoietic Stem Cell Transplantation;Homeostasis;Immune;immune function;Immune system;Immune Targeting;Immunologics;Immunosuppression;Inflammation;Infusion procedures;insight;intestinal epithelium;Intestinal Graft Versus Host Disease;Intestines;Large Intestine;leukemia;leukemia/lymphoma;Life;Link;Lymphoma;Malignant Neoplasms;Mediating;Melphalan;Metabolic;metabolomics;microbial products;microbiome;microbiota;mouse model;Mucins;Mucolytics;Mucous body substance;Mus;novel strategies;nutrition;Oral;organ transplant recipient;Pathology;Patients;Play;prebiotics;Prevalence;Process;prophylactic;Propionates;prospective;Radiation therapy;Retrospective Studies;Risk;Risk Factors;Role;Sampling;Severity of illness;Source;Specimen;stool sample;sugar;Symptoms;systemic inflammatory response;Technical Expertise;Testing;Time;Tissues;Toxic effect;translational potential;Transplant Recipients;Work

PROJECT_TITLE: Protecting colonic mucus to mitigate acute intestinal graft-versus-host disease

STUDY_SECTION: TTT

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Cancer;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Digestive Diseases;Pain Research;Pancreatic Cancer;Rare Diseases

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: NARRATIVE Chronic pancreatitis (CP) is a progressive, unrelenting disease, often leading to loss of exocrine and endocrine function and debilitating abdominal pain, resulting in significant healthcare costs. The Consortium for the study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC), formed in 2015, has been tasked with undertaking comprehensive clinical, epidemiological, and biological characterization of patients with CP (including adults and children with acute recurrent pancreatitis) to develop treatments and gain insight into the pathophysiology of CP and its sequela: chronic pain, pancreatic exocrine and endocrine insufficiency, and the diabetes/pancreatic cancer association. The Indiana University clinical center pledges to continue its contribution to ongoing CPDPC studies, and propose additional ancillary studies which will be described herein.

PI_NAMEs: FOGEL, EVAN L (contact)

PROGRAM_OFFICER_NAME: UNALP-ARIDA, AYNUR

PROJECT_TERMS: Abdominal Pain;Acute;Adult;Ancillary Study;anti-epileptic agents;Bicarbonates;Biological;Biological Markers;biomarker development;biomedical referral center;blood glucose regulation;candidate marker;carbohydrate binding protein;carbohydrate receptor;Characteristics;Child;Childhood;chronic pain;chronic pancreatitis;Clinical;clinical center;clinical practice;Clinical Research;Clinical Treatment;cohort;comparative efficacy;cost;Data;dermatome;Development;Diabetes Mellitus;Diagnosis;Disease;Disease Progression;Dose;Dose Limiting;Duct (organ) structure;Duodenum;Early Diagnosis;early onset;effective therapy;Endocrine;Enrollment;Epidemiology;Excision;Exocrine pancreas;experience;Extracorporeal Shockwave Lithotripsy;fibrogenesis;Fibrosis;Functional disorder;Funding;Galectin 3;genetic variant;Glucose Metabolism Disorders;Goals;health assessment;Health Care Costs;health care service utilization;high risk;Hormonal;Human;Hyperalgesia;improved;Indiana;Individual;individual patient;inhibitor;innovation;insight;Intervention;Investigation;Lead;Liquid substance;Lithotripsy;Liver Fibrosis;Longitudinal Studies;Magnetic Resonance Cholangiopancreatography;Magnetic Resonance Imaging;Main pancreatic duct;Malignant neoplasm of pancreas;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;Onset of illness;Operative Surgical Procedures;Opioid;opioid therapy;opioid use;Organ;Pain;Pain management;pain relief;pain score;Pancreas;Pancreatic Duct Stone;pancreatic juice;Patient Care;patient subsets;Patients;Phase;phase 1 study;pilot trial;Placebos;Population;predict clinical outcome;pressure;primary endpoint;primary outcome;Procedures;profiles in patients;Progressive Disease;Quality of life;Randomized;randomized trial;Randomized, Controlled Trials;Research;Research Design;Research Personnel;Resources;response;Risk;Risk Factors;Safety;secondary outcome;Secondary to;Sensory;Serum;Site;success;System;Testing;Tissues;tool;Toxic effect;treatment response;United States National Institutes of Health;Universities

PROJECT_TITLE: Indiana University (IU) Clinical Center for Chronic Pancreatitis Clinical Research Network


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

ORG_CITY: PISCATAWAY

ORG_DEPT: NUTRITION

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

ORG_STATE: NJ

PHR: This proposal aims to uncover new mechanisms that are responsive to amino acid insufficiency in the liver of mice. The work is relevant to public health and the mission of the NIH because it addresses the NIH 2020- 2030 Strategic Plan for Nutrition Research by asking how amino acid insufficiency affects us and when it matters.

PI_NAMEs: ANTHONY, TRACY G. (contact);WEK, RONALD C

PROGRAM_OFFICER_NAME: MARUVADA, PADMA

PROJECT_TERMS: Acids;activating transcription factor 4;Address;Affect;Aging;Amino Acids;Apoptotic;Binding;Biogenesis;biological adaptation to stress;cardiometabolism;CCAAT-Enhancer-Binding Proteins;Chemicals;Chronic Disease;Circadian Rhythms;combinatorial;Complex;Data;Dependence;Development;Diet;dietary;Disease;Diurnal Rhythm;Eukaryotic Initiation Factor-2;Event;Experimental Models;Exposure to;Fatty Liver;fitness;FRAP1 gene;Gene Targeting;Genetic;Genetic Transcription;Growth;Health;healthspan;Hepatic;Homologous Protein;improved;in vivo;Intervention;Late Effects;Life Style;lipid metabolism;Liver;liver development;liver metabolism;LoxP-flanked allele;Maintenance;Measurement;Metabolic;Metabolism;metabolome;Mission;Molecular;Monitor;mouse model;Mus;novel;Nutrient;nutrition;Nutritional Study;Outcome;paralogous gene;pathogen;Pathway interactions;Pharmacologic Substance;Phosphorylation;Phosphotransferases;Physiological;prevent;promote resilience;Protein Biosynthesis;Proteins;Proteome;proteostasis;proteotoxicity;Public Health;Publishing;Regulation;Reporting;Research;resilience;Resistance;response;restraint;Ribosomes;sensor;Sentinel;Signal Pathway;Signal Transduction;Strategic Planning;Stress;therapeutic development;transcription factor;Transcriptional Regulation;transcriptome;Translating;Translations;translatome;United States National Institutes of Health;Work

PROJECT_TITLE: Homeostatic Responses to Amino Acid Insufficiency

STUDY_SECTION: INMP

STUDY_SECTION_NAME: Integrative Nutrition and Metabolic Processes Study Section[INMP]


NIH_SPENDING_CATS: Antimicrobial Resistance;Infectious Diseases;Malaria;Natural Products;Orphan Drug;Rare Diseases;Vector-Borne Diseases

ORG_CITY: IOWA CITY

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative Combatting resistance is a critical priority in treatment of malaria, and requires continued effort in discovery and development of new antimalarial drug candidates. The recently discovered polyketide natural product bastimolide A is a new potential lead compound for antimalarial drug discovery, and its structural features are unlike other drug candidates, suggesting there may be a novel mechanism of action which could help combat resistance. Using new methods and strategies for 1,5-polyol synthesis, we will (a) synthesize bastimolide A and analogs, including chemoproteomics probes, and (b) evaluate their antiplasmodial potency, improve pharmacological properties, and identify protein(s) and lifecycle stage(s) targeted.

PI_NAMEs: FRIESTAD, GREGORY K (contact)

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: Address;analog;Anti-malarials;aqueous;artemether;Artemisinins;Binding Proteins;Biological;Biotinylation;Catalysis;Cells;Cessation of life;chemoproteomics;Child;Chloroquine;Chloroquine resistance;Clinical;clinical application;Clinical Trials;combat;Combined Modality Therapy;complement C2a;Cyclization;Data;Development;Doxycycline;drug candidate;drug discovery;Drug resistance;drug resistance development;effective therapy;Evaluation;experience;Exploratory/Developmental Grant;Feedback;functional group;Funding;Geography;HepG2;improved;indexing;infectious disease treatment;innovation;Investigational Drugs;Isomerism;Lactones;Lead;Life Cycle Stages;Liver;Macrolides;Malaria;Measurement;member;Methodology;Methods;Microsomes;Natural Products;Natural Products Chemistry;Natural Source;novel;novel strategies;novel therapeutics;Parasites;pathogen;Permeability;Pharmaceutical Chemistry;pharmacologic;pharmacophore;Phase;Plasma Proteins;Plasmodium falciparum;polyketides;polyol;Primaquine;programs;Property;Proteins;Quinine;Research Project Grants;Resistance;resistant Plasmodium falciparum;resistant strain;screening program;Signal Transduction;Solubility;Stereoisomer;Structure;tool;Toxic effect;World Health Organization

PROJECT_TITLE: Synthetic studies and antimalarial activities of bastimolides and related polyketides

STUDY_SECTION: SBCB

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


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Physical Injury - Accidents and Adverse Effects;Rehabilitation

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: PROJECT NARRATIVE Almost 30 million tendon injuries are reported each year, but therapeutic techniques produce mixed successes, with 0-85% of patients showing improvement. We have shown that focused ultrasound (fUS) can be used to create mild collagen fiber fraying and separation in rat tendons, and that the fUS treatment preserves mechanical properties of tendons as well as or better than the conventional dry needling. Our objective is to develop fUS therapy for the treatment of chronic tendinopathies and integrate passive cavitation and tissue Doppler imaging for quantitative feedback of the fUS therapy.

PI_NAMEs: SIMON, JULIANNA  (contact)

PROGRAM_OFFICER_NAME: KING, RANDY LEE

PROJECT_TERMS: Acoustics;Affect;Animals;Anisotropy;Annual Reports;biomechanical model;Biomechanics;Chronic;Collagen;Collagen Fiber;collagenase;common treatment;cost;cost estimate;Development;Devices;Dose;Dryness;Elasticity;experimental study;Family suidae;Feedback;Focused Ultrasound;Focused Ultrasound Therapy;Fractionation;Gel;healing;Human;Hydrogels;Image;improved;in vivo;Injections;injured;Injury;innovation;Insulin-Like Growth Factor I;Location;loss of function;mechanical properties;Mechanics;Modeling;Monitor;Needles;novel;Pain;patient variability;Patient-Focused Outcomes;Patients;Perfusion;personalized medicine;Photography;Physical therapy;porcine model;Predisposition;preservation;Property;Protocols documentation;Publications;quantitative imaging;quantitative ultrasound;Rattus;real time monitoring;real-time images;Reporting;response;Severities;Shock;Speed;success;Techniques;Tendinopathy;Tendon Injuries;Tendon structure;Testing;TGFB1 gene;Therapeutic;therapy development;Time;Tissues;traditional therapy;Transducers;Transforming Growth Factor beta;Transforming Growth Factors;Translations;treatment effect;treatment planning;ultrasound;United States;Work

PROJECT_TITLE: Focused ultrasound-induced cavitation in elastic, anisotropic tissues: a treatment for tendinopathies

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Biotechnology;Brain Disorders;Cerebrovascular;Dementia;Lymphatic Research;Neurodegenerative;Neurosciences;Rehabilitation;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: CLEVELAND

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: NARRATIVE  The objective of this project is to develop magnetic resonance imaging methods for in vivo evaluation of glymphatic function. The methods will be applied to investigate the role of AQP4 and the glymphatic system in post-stroke edema formation and reabsorption. Such investigation will enhance our understanding of post-stroke pathophysiology, leading to improved patient care.

PI_NAMEs: FLASK, CHRISTOPHER A;YU, XIN  (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: 3-Dimensional;absorption;acute stroke;Adult;Affect;aquaporin 4;Area;Brain;Brain Edema;Brain hemorrhage;Brain Injuries;brain parenchyma;brain tissue;Cause of Death;Cerebral Edema;Cerebrospinal Fluid;cerebrospinal fluid flow;Cerebrovascular Circulation;Cerebrum;Cessation of life;cisterna magna;clinically significant;Complex;Complication;contrast enhanced;Contrast Media;cytotoxic;Development;disability;disability burden;Edema;Evaluation;Fingerprint;Functional disorder;Future;Gadolinium;Garbage;genetic manipulation;glymphatic flow;glymphatic function;glymphatic system;Goals;Hemorrhage;Hour;Human;Image;imaging modality;Impairment;improved;in vivo;in vivo evaluation;Infarction;Infusion procedures;inhibitor;insight;Intercellular Fluid;interstitial;Intracranial Hypertension;Investigation;Ischemia;Ischemic Stroke;Kinetics;Knock-out;Knockout Mice;Laboratory Animals;Life;Liquid substance;Long term disability;long term recovery;Magnetic Resonance;Magnetic Resonance Imaging;Measurement;Measures;Metabolic;Methods;Middle Cerebral Artery Occlusion;Modeling;molecular size;Molecular Weight;mouse model;Mus;Nervous System Disorder;new therapeutic target;novel;novel strategies;Operative Surgical Procedures;Oxygen;Pathway interactions;Patient Care;Perfusion;Physiological;Play;post stroke;preservation;Process;Recovery of Function;Reporting;Resistance;Role;Scanning;solute;Stroke;stroke event;stroke model;stroke recovery;Subarachnoid Hemorrhage;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;Time;Tissue Preservation;Tissues;Tracer;two photon microscopy;vasogenic edema;Waste Products;wasting;Water;water channel

PROJECT_TITLE: AQP4 and glymphatic function in post-stroke recovery


NIH_SPENDING_CATS: Autoimmune Disease;Congenital Structural Anomalies;Digestive Diseases;Inflammatory Bowel Disease;Microbiome;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE The importance of the enteric and autonomic nervous systems for maintaining intestinal health is evident in Hirschsprung’s disease (HSCR), defined by the absence of enteric ganglia in distal bowel and caused by a number of mutations that phenocopy the disease in mouse models. This research proposal will investigate neural interactions with the microbiome and immune system that regulate inflammation and determine the role of the microbiome in mediating persistent functional and inflammatory issues experienced by HSCR patients with the hope of facilitating the development of mechanism-based therapeutics to alleviate these chronic bowel complications.

PI_NAMEs: SMITH-EDWARDS, KRISTEN MICHELLE (contact)

PROGRAM_OFFICER_NAME: CUMMINGS, DIANA M

PROJECT_TERMS: 16S ribosomal RNA sequencing;Adult;Affect;Age;Anatomy;Autonomic nervous system;Biological Assay;Calcium;calcium indicator;Cell Count;Cells;Child;Childhood;Chronic;Clinical;Colon;Communication;Complication;Congenital Abnormality;Congenital Megacolon;Data;Defect;Development;Digestive System Disorders;Disease;disease diagnosis;disease model;Distal;dysbiosis;Electrophysiology (science);Endothelin;Enteral;Enteric Nervous System;Enterocolitis;epithelial injury;Etiology;Exhibits;experience;experimental study;fecal transplantation;Flow Cytometry;Functional disorder;Ganglia;Genes;Goals;Health;Heterozygote;Human;Image;Immune;immune function;Immune system;Immune System Diseases;Immunity;Impairment;in vivo;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Intestines;Lamina Propria;Life;life span;loss of function mutation;Measures;Mediating;microbial;microbiome;microbiome composition;microbiota;Microscopy;Modeling;Motility;motility disorder;mouse model;Mucosal Immunity;Mus;Mutation;Nerve;nerve supply;neural;Neuroimmune;neuromechanism;Neuronal Dysfunction;Neurons;Newborn Infant;novel;Operative Surgical Procedures;Pathway interactions;Patients;Phenocopy;Phenotype;postnatal;Predisposition;Preparation;prevent;Prevention;Probiotics;programs;receptor;Reporting;Research;Research Proposals;Risk;Role;sensory input;Siblings;Signal Transduction;Sodium Dextran Sulfate;Symptoms;Synapses;Technical Expertise;Techniques;Testing;Therapeutic;Training;Visceral pain

PROJECT_TITLE: Neural interactions with the microbiome and immune system that produce inflammation in Hirschsprung disease models

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


NIH_SPENDING_CATS: Genetics

ORG_CITY: AMHERST

ORG_DEPT: BIOLOGY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

ORG_STATE: NY

PHR: PROJECT NARRATIVE RNA misfolding has been linked to human disease and is a major challenge for the development of RNA biotechnology, but our current understanding of how nascent RNA folds during transcription is limited. Using riboswitches as a model system, we will develop high-throughput tools to investigate how transcription coordinates the formation of biologically functional RNA structures and how perturbing these processes can cause RNA misfolding. This work will uncover basic principles of cotranscriptional RNA structure formation that will advance our ability to engineer RNA systems for biomedical applications, and predict how mutations cause RNA to fold into dysfunctional structures.

PI_NAMEs: STROBEL, ERIC J (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Address;Affect;Biochemical Reaction;Biological Models;Biology;Biotechnology;Catalysis;Cell Physiology;Cells;combinatorial;Development;DNA-Directed RNA Polymerase;Engineering;Gene Expression Regulation;Genetic Transcription;Genome;human disease;Kinetics;Knowledge;Ligands;Link;Mediating;Methods;Mutation;Process;Research;RNA;RNA Folding;RNA Sequences;Structure;System;tool;Transcriptional Regulation;Untranslated RNA;Work

PROJECT_TITLE: Mechanisms of cotranscriptional RNA structure formation

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE The Drosophila neuromuscular junction is a model synapse that uses multiple neuromodulators for neurons to control muscle contractions and electrochemical sensors could be ideal for interrogating this signaling as they can follow neuromodulation in real time. In this proposal, we will develop new electrode fabrication technologies based on carbon nanomaterials, 3D printing, and Si-based microelectromechanical systems (MEMS) strategies and apply these electrodes to neuromodulator measurements in the Drosophila NMJ and in vivo. With a focus on easy, batch fabrication, these electrodes will be made available to the neuroscience community, to facilitate studies of real-time neuromodulation and how it malfunctions during disease.

PI_NAMEs: VENTON, B. JILL (contact)

PROGRAM_OFFICER_NAME: KUMSA, DOE WONDWOSSEN

PROJECT_TITLE: Tunable Carbon Electrodes for in vivo Neurotransmitter Detection

STUDY_SECTION: BNVT

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


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Social Determinants of Health;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE: State-level pregnancy termination policies have dramatically changed over the past decade. Only limited research examines the population-level maternal and child health impacts of such policies, and research to date has not identified subgroups most at risk of experiencing an adverse outcome or state-level conditions that might buffer such adverse effects. Understanding maternal and child health effects of these policies is crucial to prepare public health and health care systems to care for groups most affected by policies and to implement other strategies to buffer adverse impacts.

PI_NAMEs: ROBERTS, SARAH C.M. (contact)

PROGRAM_OFFICER_NAME: POPKIN, RONNA

PROJECT_TERMS: Achievement;Address;Adoption;adverse birth outcomes;Adverse effects;Adverse event;adverse outcome;Affect;Age;Birth;Buffers;Caring;Characteristics;Child;Code;Country;court;Data;Data Analyses;Data Set;Databases;Development;Disparity population;econometrics;Economics;Epidemiologic Methods;Epidemiology;epidemiology study;Ethnic Origin;Exposure to;Funding;Future;gender equality;Geography;Healthcare Systems;Hearing;Heterogeneity;improved;Income;Individual;Inequity;Infant Mortality;Infrastructure;innovation;insurance claims;Legal;Legal Status;Licensing;Low Birth Weight Infant;Maternal and Child Health;maternal morbidity;Maternal Mortality;Measures;meetings;Methodology;Methods;Modification;Monitor;National Institute of Child Health and Human Development;Neonatal Mortality;Outcome;Persons;physical conditioning;Policies;Population;Pregnancy;pregnant;Premature Birth;Prevention approach;Prevention strategy;Public Health;public policy on alcohol;Race;racial difference;Reduce health disparities;Research;response;Risk;Risk Assessment;Services;severe maternal morbidity;Severities;Socioeconomic Status;Structural Racism;Subgroup;Surveys;System;Termination of pregnancy;Testing;Time;trend;Vital Statistics;Woman;Women's Health

PROJECT_TITLE: State-level factors and maternal and child health outcomes

STUDY_SECTION: SSPA

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


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

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: PROJECT NARRATIVE HIV infection has major impacts on human health in the US and worldwide. Understanding the basis of immune cell activation and broadly neutralizing antibody production using controlled presentation of HIV immunogens on the nanoscale offers important opportunity for the development of effective vaccines to prevent and treat HIV infections worldwide.

PI_NAMEs: BATHE, MARK  (contact);IRVINE, DARRELL J

PROGRAM_OFFICER_NAME: MALASPINA, ANGELA

PROJECT_TERMS: 3-Dimensional;Acquired Immunodeficiency Syndrome;adaptive immune response;Adjuvant;Affinity;Agonist;Animal Model;Antibody Affinity;Antibody Formation;Antigen Presentation;Antigen-Presenting Cells;Antigens;Artificial nanoparticles;B-Cell Activation;B-Cell Antigen Receptor;B-Cell Receptor Binding;B-Lymphocytes;Bathing;Benchmarking;Biodistribution;Biological Assay;Biomedical Engineering;Calcium Signaling;Cell model;Cells;cellular imaging;Cellular Immunity;Characteristics;clinical development;clinically relevant;Communicable Diseases;Confocal Microscopy;crosslink;Cues;density;design;Development;Dimensions;DNA;Engineering;Ensure;env Gene Products;Evaluation;Event;experience;flexibility;fluorescence imaging;Germ Lines;Health;Hepatitis B Vaccines;Heterogeneity;HIV;HIV envelope protein;HIV Envelope Protein gp120;HIV Infections;HIV vaccine;HIV-1;Human;human model;Human Papilloma Virus Vaccine;Humoral Immunities;Image;Immobilization;Immune;immune activation;Immune response;Immunologic Adjuvants;Immunology;In Vitro;in vivo;in vivo evaluation;Infection;Innate Immune Response;Investigation;Licensing;Ligands;link protein;lymph nodes;Memory;Modeling;Modification;mouse model;nanocluster;nanometer;nanoparticle;nanoparticulate;nanoscale;Nanotechnology;neutralizing antibody;pandemic disease;particle;pathogen;Pathway interactions;Peripheral;preclinical development;preservation;prevent;Receptor Activation;Receptor Signaling;response;Role;scaffold;Scaffolding Protein;Signal Transduction;Stimulus;Structure;Subunit Vaccines;Surface;synthetic construct;T-Lymphocyte;Technology;Testing;Toll-like receptors;tool;translational potential;ultra high resolution;Vaccination;Vaccine Design;vaccine development;vaccine formulation;Vaccines;Variant;Viral;Virus-like particle;Visualization

PROJECT_TITLE: Investigation of Synthetic DNA-based Viral Particles for Spatially Controlled Antigen Presentation

STUDY_SECTION: NANO

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Pain Research;Prevention

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative Chronic post-surgical pain (CPSP) is a significant public health concern affecting up to 80% of adults who have undergone surgery and is a contributor to the opioid epidemic. Identification of biopsychosocial risk factors is crucial for pain prevention and more effective treatment strategies. The proposed translational research plan will utilize a prospective study design as well as a mechanistic clinical trial to address substantial gaps in the literature, including neurological mechanisms underlying behavioral treatment response.

PI_NAMEs: SIEBERG, CHRISTINE BARRETT (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Address;Adolescence;Adolescent;Adult;Affect;age difference;Animal Model;Behavior Therapy;Behavioral;biopsychosocial;Brain;Chronic;Clinic;Clinical;Clinical Trials;Collaborations;Diagnosis;effective therapy;emotional functioning;evidence base;Evolution;functional near infrared spectroscopy;Funding;Goals;Grant;improved;Individual;Intervention;Laboratories;life span;Literature;Measures;Mentored Patient-Oriented Research Career Development Award;Modeling;Neurobiology;neuroimaging;Neurologic;Neurosciences;Operative Surgical Procedures;opioid epidemic;Pain;patient oriented;Patients;Persistent pain;Persons;pharmacologic;Physical Function;Postoperative Pain;pre-clinical;prescription opioid;Prevention;Process;programs;Prospective Studies;psychologic;Psychophysics;Public Health;Publishing;Quality of life;Research;Research Design;resilience;Risk Factors;Severities;Signal Transduction;surgical risk;Synaptic plasticity;translational approach;Translational Research;treatment as usual;treatment response;treatment strategy;Vision;Work

PROJECT_TITLE: Chronic Postsurgical Pain Across the Lifespan: Brain State and Treatment

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


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: Project Narrative This training grant will support the career development of graduate students in immunology at the  University of Minnesota. It is highly relevant to public health because these young scientists will  produce tomorrow's new vaccines and cures for autoimmunity and cancer.

PI_NAMEs: HOGQUIST, KRISTIN A. (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Immunology;Training Programs

PROJECT_TITLE: Immunology Training Program

STUDY_SECTION: AITC

STUDY_SECTION_NAME: Allergy, Immunology, and Transplantation Research Committee[AITC]


PHR: Project Narrative This work seeks to challenge our basic understanding of the biochemical networks that are important to how cells make decisions. In addition to improving our basic understanding, this work could help to open new avenues for the treatment of diabetes, inﬂammation, and cancer.

PI_NAMEs: NAEGLE, KRISTEN M (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Address;Biochemical;Cell Physiology;Cell Signaling Process;Cells;Cues;Decision Making;Diabetes Mellitus;Disease;extracellular;falls;Growth;Human;improved;In Vitro;Inflammation;Location;Malignant Neoplasms;Mediating;new therapeutic target;novel;Outcome;Phenotype;Phosphorylation;Physiological;Proteome;Role;Signal Transduction;Site;Specificity;Tertiary Protein Structure;Testing;Tyrosine;Tyrosine Phosphorylation;Tyrosine Phosphorylation Site;Work

PROJECT_TITLE: Systematic approaches to reveal novel regulatory functions of tyrosine phosphorylation

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


NIH_SPENDING_CATS: Autoimmune Disease;Neurodegenerative;Neurosciences;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Traumatic Head and Spine Injury

ORG_DEPT: NEUROSCIENCES

PHR: Project Narrative Since neural degeneration is an important component of the response to neural trauma and is a consequence of a number of neurological diseases, it is a major public health problem. We have reported the unexpected finding that a group of immune cells thought to be required for clearing debris from degenerating nerves is not required, and we present the first evidence that a quite different group of immune cells is required for this process. We will explore in depth the cells and receptors required for this clearance and therefore for nerve regeneration.

PI_NAMEs: ZIGMOND, RICHARD E (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Acute;Animal Model;antagonist;Anti-Inflammatory Agents;Antibodies;Attention;Axon;Axotomy;B-Lymphocytes;Brain;CCL2 gene;cell type;Cells;Central Nervous System;chemokine;chemokine receptor;Confocal Microscopy;CXCL1 gene;CXCL2 gene;Demyelinating Diseases;Demyelinations;Disease;Disease Progression;Distal;Electron Microscopy;Electrophysiology (science);Enzyme-Linked Immunosorbent Assay;Excision;Experimental Autoimmune Neuritis;experimental study;Ganglia;Genes;Growth;Guillain Barré Syndrome;IL8RB gene;Immune;improved;In Situ Hybridization;indexing;Infiltration;Inflammatory;injured;Injury;Interleukin-8B Receptor;Knock-out;Knockout Mice;Lesion;Macrophage;Measures;Modeling;monocyte;monocyte chemoattractant protein 1 receptor;mouse model;Multiple Sclerosis;Mus;Myelin;Myelin Proteins;Natural regeneration;Nerve;Nerve Crush;Nerve Degeneration;Nerve Regeneration;nerve transection;Nervous System;Nervous System Disorder;neural;Neural Conduction;Neuroglia;Neuroimmune;neuroinflammation;Neurons;Neuropathy;neutralizing antibody;neutrophil;Neutrophil Infiltration;novel;Oils;Pathologic;Pathology;Peripheral;Peripheral Nervous System;Peripheral Nervous System Diseases;Phagocytes;Phagocytosis;pharmacologic;Phenotype;Play;Population;Process;Proteins;Public Health;receptor;Recovery of Function;regenerative;Reporting;response;Role;Schwann Cells;sciatic nerve;Spinal Cord;Stains;T-Lymphocyte;Techniques;Time;Tissues;Tolonium chloride;Trauma;Wallerian Degeneration;Western Blotting;Wild Type Mouse

PROJECT_TITLE: Neuroinflammation in Wallerian Degeneration and Regeneration: Neutrophils Play a Primary Role as Phagocytes

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Project Narrative Although highly effective anti-HIV drugs are available and are making an impact on HIV control, HIV epidemic is still a major health problem. This long-standing training program is dedicated to training individuals who wish to secure their PhD or M.D./PhD dual degrees in HIV/AIDS Research and to offer advanced training in specialized HIV/AIDS topics to those who have already obtained a PhD Or MD degrees. An outstanding roster of training faculty and research topics that are aligned with national priorities assure a high quality, targeted training of individuals who will form the future workforce that tackles the AIDS epidemic in the coming years.

PI_NAMEs: PRASAD, VINAYAKA R. (contact)

PROGRAM_OFFICER_NAME: REFSLAND, ERIC WILLIAM

PROJECT_TITLE: Training in HIV/AIDS Pathogenesis; Basic and Translational Research

STUDY_SECTION: AIDS

STUDY_SECTION_NAME: Acquired Immunodeficiency Syndrome Research Study Section[AIDS]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

ORG_CITY: DALLAS

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative While the environment, nutrition, and genetic factors play a major role in the metabolic aspects of aging, recent studies have suggested maternal metabolism can have a profound impact on progeny lifespan, physiology, and susceptibility to metabolic diseases. Our work examines how metabolic disruptions in oocytes reprogram progeny metabolism and aging. Insights gained from these studies provide a foundation to understand how changes in metabolic state of a mother can shorten lifespan in children by increasing incidence of metabolic disfunction.

PI_NAMEs: SIEBER, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: FU, YI-PING

PROJECT_TERMS: Adult;aged;Aging;Animals;Biochemical;Biological Models;blood glucose regulation;cancer initiation;carbohydrate metabolism;Cell Lineage;Cell model;Cells;Cellular Metabolic Process;Child;ChIP-seq;Chromatin;Complex;Data;Defect;Development;diabetic;Diabetic mother;disability;Disease;Disease susceptibility;DNA;Drosophila genus;Embryo;Environment;Environmental Risk Factor;Epigenetic Process;Equilibrium;Exhibits;experimental study;Female;Foundations;Functional disorder;Genes;Genetic;Genetic Transcription;Germ Lines;Glucose;Glutathione;Glycogen;Goals;Health;healthspan;Heritability;Histone Acetylation;histone methylation;Homeostasis;Human;in vivo;Incidence;Individual;Inherited;insight;Insulin;insulin signaling;Intestines;Life;life span;Lipids;male;Mammalian Cell;Mediating;Metabolic;metabolic abnormality assessment;Metabolic Diseases;Metabolic dysfunction;Metabolic syndrome;Metabolism;metabolomics;Methods;Mitochondria;Modeling;Molecular;Mothers;Mus;novel;Nuclear;Nutrient;nutrition;offspring;Oocytes;Oogenesis;oxidation;Oxidation-Reduction;Partner in relationship;Persons;Phenotype;Physiology;Play;Predisposition;premature;Prevalence;Process;programs;Promoter Regions;Research;respiratory;Risk;Role;Signal Transduction;Small RNA;Speed;sperm cell;stem cells;System;Testing;Tissues;tool;transcription factor;transmission process;Triglyceride Metabolism;Triglycerides;tumor progression;Work

PROJECT_TITLE: Investigating the role of maternal metabolic reprogramming in progeny physiology and aging

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;HIV/AIDS;Infectious Diseases

PHR: A hallmark of HIV infection is intestinal inflammation and loss of gut epithelial integrity, which result in translocation of gut bacteria into the circulation, chronic systemic immune activation, and HIV disease progression. In this proposal we will utilize novel in vivo and ex vivo model systems and cutting-edge technologies to investigate the mechanism by which HIV infection results in death of intestinal epithelial cells and disrupted barrier function. These findings may inform the development new strategies to target gut integrity and improve outcomes for people living with HIV.

PI_NAMEs: KWON, DOUGLAS  (contact);YILMAZ, OMER

PROGRAM_OFFICER_NAME: GREENWEL, PATRICIA

PROJECT_TERMS: Address;antiretroviral therapy;Apoptosis;Autologous;Bacteria;Biological Assay;Biological Markers;Biological Models;Biopsy;Blood;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Death;Cell model;Cells;Cellular biology;Cessation of life;Chronic;Circulation;cohort;Colon;Data;Defect;Development;Disease;Disease Progression;Endoscopy;Epithelial Cells;Epithelium;exhaustion;fatty acid metabolism;Functional disorder;gastrointestinal;gastrointestinal epithelium;Genetic Transcription;Gut associated lymphoid tissue;gut bacteria;gut inflammation;Heart Diseases;Histology;HIV;HIV Infections;Homeostasis;Human;Hyperglycemia;Immune;immune activation;Immune System Diseases;Immunology;Impairment;improved;improved outcome;In Situ;in vivo;in vivo Model;Individual;Inflammation;Inflammatory;Inflammatory Bowel Diseases;intestinal barrier;intestinal epithelium;Intestinal Mucosa;Intestinal permeability;Intestines;Knowledge;Lipids;Massachusetts;Measures;Mediating;Membrane Lipids;Metabolic;microbial;microbial products;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mucous Membrane;Mus;novel;Nutritional;Organoids;Pathogenesis;Pathologist;Pathology;Pathway interactions;Peripheral;Permeability;Persons;Phenotype;Population;Positioning Attribute;Process;Regimen;Regulation;Role;Sample Size;Sampling;self-renewal;single cell sequencing;Stroke;systemic inflammatory response;T-Lymphocyte;Technology;Testing;Tissue Sample;Tissues;transcriptome sequencing;Virus Diseases;Virus Replication

PROJECT_TITLE: Immunometabolic regulation of CD8+ T cell mediated intestinal epithelial cell death in people with HIV (PWH)


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Lewy Body Dementia;Neurodegenerative;Neurosciences;Parkinson's Disease

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative This project will improve our understanding of mechanisms underlying the development of cognitive impairment in Parkinson disease, which is needed to guide the development of treatments for Parkinson disease.

PI_NAMEs: KOTZBAUER, PAUL T (contact)

PROGRAM_OFFICER_NAME: SWANSON-FISCHER, CHRISTINE R

PROJECT_TERMS: abeta accumulation;Address;Affect;alpha synuclein;Alzheimer's disease related dementia;Amyloid beta-Protein;Attention;Autopsy;Basal Ganglia;Basal Nucleus of Meynert;Biological Assay;Biological Markers;Brain region;brain tissue;Carrier Proteins;Cell Nucleus;cholinergic;Cognition;Cognitive;cognitive function;cognitive impairment in Parkinson's;Consent;Corpus striatum structure;Dementia;Deposition;Development;dorsal raphe nucleus;Enzyme-Linked Immunosorbent Assay;executive function;Freezing;Functional disorder;Gait;Goals;High Pressure Liquid Chromatography;Immunohistochemistry;Impaired cognition;Impairment;improved;Individual;Lewy Bodies;Lewy Body Dementia;locus ceruleus structure;Longitudinal cohort;Longitudinal Studies;Measures;Memory;Methods;misfolded protein;motor symptom;neocortical;Nerve Degeneration;nerve supply;neurobehavioral;neuron loss;Neurons;Neurotransmitters;noradrenergic;novel strategies;Outcome Measure;Parkinson Disease;Parkinson's Dementia;Participant;Pathologic;Pathology;Patients;Pattern;Persons;Phenotype;postsynaptic;presynaptic;Presynaptic Terminals;protein aggregation;protein biomarkers;Proteins;Sampling;Substantia nigra structure;tau aggregation;tau Proteins;Thalamic structure;therapeutic target;Therapeutic Trials;therapy development;Time;Tissue Sample;Tissues;Visuospatial

PROJECT_TITLE: Protein Aggregation and Neurotransmitter Deficits in Parkinson Disease

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Aging;Breast Cancer;Cancer;Estrogen;Genetics;Nutrition;Obesity;Women's Health Research

ORG_CITY: WASHINGTON

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: Project Narrative Obesity is associated with increased estrogen receptor-positive (ER+) breast cancer (BC) risk and a 2-4 fold increase in mortality across all BC subtypes, but mechanisms of increased acquired resistance to therapy and ensuing fatal BC metastasis in obesity remain unclear. This project studies how the estrogen, estrone (E1), which dominates after menopause and is much higher in obese local mammary fat, co-operates with ER/ NFκB and the Receptor for Advanced Glycation End-products (RAGE) in BC cells, adipocytes, and the tumor microenvironment to impair drug treatment responses. Preclinical studies in organoids and PDX models test the ability of new RAGE inhibitor drugs to reverse acquired endocrine therapy resistance.

PI_NAMEs: HUDSON, BARRY IAN (contact);SLINGERLAND, JOYCE MARIE

PROGRAM_OFFICER_NAME: BERA, TAPAN K

PROJECT_TERMS: acquired drug resistance;Adipocytes;American;Automobile Driving;Binding;Biological Assay;Breast Cancer Cell;breast cancer metastasis;Breast Cancer Patient;Breast Cancer Risk Factor;Breast Cancer therapy;Cancer Cell Growth;Cancer Patient;cancer stem cell;cancer subtypes;CCL2 gene;cell type;Cells;Cessation of life;chemokine;clinical investigation;comorbidity;cytokine;Cytokine Gene;Data;diet-induced obesity;Disease;Drug resistance;effective therapy;Endocrine;Endothelial Cells;Environment;ESR1 gene;Estrogen Antagonists;Estrogen receptor positive;Estrogens;Estrone;Fatty acid glycerol esters;Fulvestrant;Future;Gene Activation;Gene Expression;gene induction;Genes;Goals;Growth;hormone therapy;Human;IL6 gene;Immune;Immune Evasion;Immunologic Stimulation;immunoregulation;Impairment;In Vitro;in vivo;Infiltration;Inflammation;Inflammatory;inhibitor;inhibitor therapy;Life Style;Ligands;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;MCF7 cell;Mediating;Mediator;Modeling;mortality;mouse model;Mus;mutant;Mutation;Myeloid-derived suppressor cells;Neoplasm Metastasis;neoplastic cell;novel strategies;Obese Mice;obese patients;Obesity;obesity treatment;Oncogenic;Organoids;Outcome;patient derived xenograft model;Pharmacotherapy;Postmenopause;preclinical study;Premenopause;Preventable cancer cause;programs;receptor for advanced glycation endproducts;recruit;Repression;Resistance;response;Response Elements;Risk;S100A8 gene;Signal Transduction;single-cell RNA sequencing;stem cell expansion;synergism;Testing;Therapeutic;therapy resistant;Thinness;TLR4 gene;transcription factor;transcriptome;transcriptomics;treatment response;tumor;Tumor Immunity;tumor microenvironment;tumor progression;weight loss intervention;Work

PROJECT_TITLE: Targeting RAGE in tumor and TME to oppose inflammation and drug resistance in obesity associated ER+ breast cancer

STUDY_SECTION: MCTB

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics B Study Section[MCTB]


NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences

ORG_NAME: UNIVERSITY OF MASSACHUSETTS BOSTON

PHR: Narrative We will maximize the effectiveness of temporal interference stimulation using computational models and experimental applications in non-human primates and humans. The work will provide definitive confirmation of noninvasive and focal stimulation in humans, and of specific deep brain targets in monkeys, and thus has the potential to transform the way we diagnose and treat patients with brain disorders.

PI_NAMEs: RAMPERSAD, SUMIENTRA MARIJKE (contact)

PROJECT_TERMS: Address;Agreement;Algorithms;Animals;Area;Behavioral;Biomedical Engineering;biophysical model;Brain;Brain Diseases;brain dysfunction;Cell Nucleus;Cephalic;Choice Behavior;Clinical;Clinical Trials Design;Computer Models;computerized tools;cranium;Data;Deep Brain Stimulation;Development;Diagnosis;discrimination task;Effectiveness;electric field;Electrodes;Electrophysiology (science);Euthanasia;experience;experimental study;FDA approved;flexibility;Frequencies;Future;Hand;Human;Implant;in silico;Investigation;Lateral Geniculate Body;Left;Magnetism;Measures;Membrane;Mental Depression;Mental disorders;metallicity;Methods;Modeling;Modification;Monkeys;Motor Cortex;Motor Evoked Potentials;multidisciplinary;Mus;Muscle;Nervous System Disorder;neural;neural circuit;Neurons;neuroregulation;Neurosciences;nonhuman primate;noninvasive brain stimulation;novel;novel strategies;Outcome;Output;Pathology;Patients;Pattern;Phase;Positioning Attribute;Primates;Protocols documentation;Reporting;Resistance;Resolution;response;Risk;Rodent;Safety;Scalp structure;Stimulus;System;Temporal Lobe;Testing;Therapeutic;tool;Visual;visual discrimination;Work

PROJECT_TITLE: Overcoming the Barriers to Effective Transcranial Temporal Interference Stimulation in Humans

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-NV-Q(91)S]


NIH_SPENDING_CATS: Cancer;Colorectal Cancer;Dietary Supplements;Digestive Diseases;Endocrine Disruptors;Microbiome;Nutrition;Prevention

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative: The overarching goal of the current project is to interrogate the biological role of the G- protein-coupled receptor GPR109A in colonic epithelia and immune cells and the involvement of the ketogenesis pathway in the colon and the metabolites of commensal bacteria in the activation of this receptor. We will investigate how GPR109A and colonic ketogenesis protect against colon cancer and test the hypothesis that GPR109A activation stabilizes the tumor suppressor p53 and its effector signaling. If successful, our study will provide a molecular link between bacteria-generated xenobiotics to colon cancer prevention.

PI_NAMEs: THANGARAJU, MUTHUSAMY  (contact)

PROGRAM_OFFICER_NAME: GUNASEKHARAN, VIGNESH KUMAR

PROJECT_TERMS: Affect;Affinity;Agonist;American;Anti-Inflammatory Agents;Azoxymethane;Bacteria;Benzo(a)pyrene;beta-Hydroxybutyrate;Binding;Biological;Biological Process;Butyrates;cancer cell;Cancer Model;cancer prevention;cancer therapy;carcinogenesis;Carcinogens;Cell Surface Receptors;Cells;Cessation of life;chemical carcinogen;Chemical Models;Colon;colon bacteria;colon cancer prevention;Colon Carcinoma;Colonic inflammation;commensal bacteria;Coupled;Deacetylase;Deacetylation;Dendritic Cells;Diagnosis;Diet;dietary carcinogenesis;Disease;Dose;Dyslipidemias;environmental chemical;Enzymes;Epithelium;Evaluation;Exposure to;FDA approved;Fermentation;Frequencies;Functional impairment;G-Protein-Coupled Receptors;Gene Modified;Genetic Transcription;Genetically Engineered Mouse;Goals;High Density Lipoproteins;Histone Deacetylase;Histone Deacetylase Inhibitor;HSP 90 inhibition;Human;Immune;Immune system;Immunologics;Impairment;Indoles;Induction of Apoptosis;Intestines;ketogenesis;ketogentic;Ketone Bodies;Knock-out;KRAS2 gene;Lamina Propria;Lead;Link;Liver;Low-Density Lipoproteins;luminal membrane;Maintenance;Malignant Neoplasms;MDM2 gene;Mediator;men;Molecular;Molecular Chaperones;Molecular Target;Mus;mutant;Mutation;Nicotinic Acids;novel;novel therapeutic intervention;novel therapeutics;Oncology;Organ;Organism;Pathway interactions;Persons;Pharmaceutical Preparations;pharmacologic;Physiological;Play;prevent;Prevention;Prevention strategy;Process;Proteins;receptor;Receptor Activation;Regulation;Regulatory T-Lymphocyte;Rejuvenation;Role;Side;Signal Transduction;SIRT1 gene;Site;Survival Rate;T-Lymphocyte;Testing;Therapeutic;therapeutic development;Time;TP53 gene;tumor;Tumor Immunity;Tumor Suppressor Proteins;Vitamins;Woman;Xenobiotics

PROJECT_TITLE: Bacteria-derived xenobiotics in colon cancer prevention: Link to GPR109A and colonic ketogenesis

STUDY_SECTION: DBDT

STUDY_SECTION_NAME: Drug and Biologic Disposition and Toxicity Study Section[DBDT]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Immunotherapy;Orphan Drug;Rare Diseases

ORG_CITY: PITTSBURGH

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: NARRATIVE In this project we investigate tumor cell-intrinsic p38 MAPK signaling as a new mechanism of resistance to immune-checkpoint inhibitors. We will address this using large-scale, high-dimensional multi-omics and spatial data as well as biologic correlatives in pre- and on-treatment biopsies from a human clinical trial combining a p38 inhibitor and anti-PD1 immunotherapy in head and neck cancer. We will further utilize a combination of bioinformatics analyses, mechanistic HNSCC syngeneic murine and in vitro experiments to validate our translational observations. Finally, we will identify and validate additional co-activated immune-resistance mechanisms to target in combination with p38 inhibitor and anti-PD1 for future clinical trial evaluation.

PI_NAMEs: BAO, RIYUE  (contact);LUKE, JASON JOHN

PROGRAM_OFFICER_NAME: CHEN, ZHONG

PROJECT_TERMS: adjudication;Advanced Malignant Neoplasm;anti-PD-1;anti-PD1 therapy;Automobile Driving;beta catenin;Bioinformatics;Biological;Biological Markers;biomarker development;Biopsy;cancer immunotherapy;Carcinogens;CD8-Positive T-Lymphocytes;Cell Communication;Cell Differentiation process;Cell Line;Cell Proliferation;Cells;checkpoint inhibition;chemokine;clinical translation;Clinical Trials;cohort;combinatorial;Computational Biology;Data;Data Set;Databases;deep learning;Dendritic Cells;Dimensions;Drug Combinations;drug repurposing;drug sensitivity;Evaluation;Exclusion;experimental study;FDA approved;Foundations;Future;Gene Expression;Genes;genomic data;Genomics;Goals;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;Heterogeneity;high dimensionality;HPV-negative head and neck cancer;Human;Human papilloma virus infection;Human Papillomavirus;Image;Image Analysis;Immune;Immune checkpoint inhibitor;immune resistance;Immunooncology;immunosuppressive macrophages;Immunotherapy;improved;improved outcome;In Vitro;in vivo;inhibitor;Interferons;Investigation;Link;liquid crystal polymer;Lymphocyte;Machine Learning;Macrophage;MAP Kinase Gene;Mass Spectrum Analysis;mathematical model;Measures;Mediating;Modality;Modeling;Molecular;Molecular Target;monocyte;mouse model;multidimensional data;multiple omics;multiplexed imaging;Mus;Mutation;neoplastic cell;new therapeutic target;Nivolumab;novel;novel therapeutic intervention;Oncogenic;Organoids;p38 Mitogen Activated Protein Kinase;Pathway interactions;patient population;Patients;Pharmaceutical Preparations;Phenotype;Phosphotransferases;Production;programmed cell death ligand 1;Property;protein protein interaction;Proteomics;public database;Public Domains;Rationalization;Research;Resistance;resistance mechanism;Resolution;response;Role;Safety;Signal Transduction;single-cell RNA sequencing;Solid Neoplasm;Spatial Distribution;Specimen;synergism;T cell infiltration;T-cell inflamed;T-Lymphocyte;targeted treatment;Testing;therapy resistant;transcriptome sequencing;Translational Research;treatment response;tumor;tumor microenvironment;Tumor-infiltrating immune cells;validation studies;Variant;Vascular Endothelial Growth Factors;Vegf inhibition;VEGFA gene

PROJECT_TITLE: Immune Exclusion in Cancer Immunotherapy

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Genetics;Heart Disease;Human Genome

PHR: PROJECT NARRATIVE More than six million Americans suffer from heart failure, a disease characterized by derangements in cardiac energy metabolism and mitochondrial function, which will cost the United States over 40 billion dollars in 2020 alone. The goal of this work is to broadly understand how metabolic and mitochondrial gene regulatory programs are maintained in the adult heart. This understanding could promote the development of novel therapeutics for this disease which represents an urgent unmet societal need.

PI_NAMEs: PADMANABHAN, ARUN  (contact)

PROGRAM_OFFICER_NAME: CHEON, YEWON

PROJECT_TERMS: Acetylation;Acute;Address;Adult;Affect;American;Animal Model;Area;ATAC-seq;Binding;Biochemical;Bioenergetics;Bioinformatics;Biological Assay;Biology;BRD2 gene;Bromodomain;Cardiac;Cardiac Myocytes;Cardiology;Cardiovascular Diseases;Cardiovascular system;career;career development;Cell model;Cells;ChIP-seq;Chromatin;Clinical;clinical training;Communication;Complex;cost;Coupled;Data;Death Rate;defined contribution;design;Development;Development Plans;Developmental Biology;Diagnosis;Disease;disease model;Down-Regulation;Elements;Energy Metabolism;Enhancers;Environment;Epigenetic Process;Equipment;experience;Family;Funding;GATA4 gene;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Goals;Heart;Heart failure;heart function;heart metabolism;Homeostasis;In Vitro;in vivo;inhibitor;insight;interest;K-Series Research Career Programs;Knowledge;Laboratories;Lysine;Macromolecular Complexes;Maps;Mediating;member;Mentors;Mentorship;Metabolic;Mitochondria;mitochondrial dysfunction;mitochondrial metabolism;Modeling;Molecular;Molecular Biology;mortality;mouse model;Mus;mutant;Mutation;Neurohormones;Nodal;novel;novel therapeutic intervention;novel therapeutics;Oxidative Phosphorylation;Pathogenesis;Persons;Phase;Phenotype;Physicians;preservation;Process;programs;protein function;Proteins;Quality of life;Reader;reconstitution;recruit;Regulation;Regulator Genes;Regulatory Element;Research;Research Personnel;Research Training;Rodent;Role;Running;scaffold;Scheme;Scientist;Series;skills;small molecule;Specificity;standard of care;stem;Techniques;Tertiary Protein Structure;Testing;Therapeutic Effect;therapeutic target;Tissues;Training;transcription factor;transcriptome sequencing;United States;Work

PROJECT_TITLE: A BRD4-GATA4 module cooperatively regulates mitochondrial bioenergetic homeostasis in the adult heart

STUDY_SECTION: MCBS

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Brain Disorders;Cannabidiol Research;Cannabinoid Research;Drug Abuse (NIDA only);Endocannabinoid System Research;Genetics;HIV/AIDS;Infectious Diseases;Natural Products;Neurodegenerative;Neurosciences;Substance Misuse;Therapeutic Cannabinoid Research

ORG_CITY: SAN ANTONIO

ORG_NAME: TEXAS BIOMEDICAL RESEARCH INSTITUTE

PHR: NARRATIVE The molecular mechanisms underlying HIV associated neurocognitive disorder, a major comorbidity that persists in 30-50% of patients undergoing combination anti-retroviral therapy, remains incompletely understood. Our ongoing studies suggest that persistent inflammatory signaling potentially driven by epigenetic alterations may drive HAND and that these changes may be beneficially modulated using cannabinoids. Knowledge from the proposed studies will provide a better understanding of the molecular basis of HIV associated neurocognitive disorder and open new avenues for the development of targeted anti-inflammatory therapies for not only HIV/SIV but also numerous other chronic neuroinflammatory diseases.

PI_NAMEs: BYRAREDDY, SIDDAPPA N;MOHAN, MAHESH  (contact)

PROGRAM_OFFICER_NAME: BORGMANN, KATHLEEN RUTH

PROJECT_TERMS: 2-arachidonylglycerol;Aberrant DNA Methylation;Acute;Affect;Agonist;Alzheimer's Disease;Anti-Inflammatory Agents;Antiinflammatory Effect;antiretroviral therapy;Apoptosis;Attention;Autopsy;Basal Ganglia;Blood;Brain;Cannabidiol;cannabinoid treatment;Cannabinoids;CASP1 gene;Cells;Central Nervous System;Cerebrospinal Fluid;chemokine;Chronic;CNR1 gene;CNR2 gene;Colon;combinatorial;comorbidity;CpG Islands;Crystallins;CXCL10 gene;cytokine;Data;daughter cell;Decision Making;Development;Disease;Disease Progression;DNA;DNA Methylation;ds-DNA;endocannabinoid signaling;Endocannabinoids;endogenous cannabinoid system;Endoplasmic Reticulum;endoplasmic reticulum stress;Epigenetic Process;Epithelium;Ethanolamines;Event;fatty acid amide hydrolase;Gene Expression;Gene Expression Profile;Generations;Genes;glial activation;Heat shock proteins;Heritability;HIV;HIV-associated neurocognitive disorder;immune activation;immune function;Immunologics;immunomodulatory strategy;immunoregulation;Infection;Inflammasome;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;innovation;Interferons;Intestines;IRF1 gene;Knowledge;life span;Lipids;lymph nodes;Lysine;Macaca;Macaca mulatta;Measures;Mediating;Memory;Mental Depression;Microglia;MicroRNAs;Mitosis;Molecular;monocyte;Movement;mRNA Expression;Multiple Sclerosis;Nature;Nervous System Disorder;neuroAIDS;Neurodegenerative Disorders;neuroinflammation;Neuronal Dysfunction;Neurons;Oxidative Stress;Oxidoreductase;Parkinson Disease;Pathogenesis;Patients;Penetration;Peripheral;Persons;Pharmaceutical Preparations;Play;PPAR gamma;prevent;Production;promoter;protein expression;Proteins;receptor;Research;Residual state;response;Risk;Role;Serum Markers;Signal Transduction;simian human immunodeficiency virus;Site;SIV;STAT2 gene;Symptoms;Testing;Tetrahydrocannabinol;Therapeutic;Time;TRPV1 gene;Up-Regulation;Viral;Viral reservoir;Virus Replication;WFS1 gene;Wolfram Syndrome

PROJECT_TITLE: Epigenetic mechanisms underlying cannabinoid modulation of neuroinflammation in HIV/SIV infection


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

ORG_CITY: ITHACA

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CORNELL UNIVERSITY

PHR: Project Narrative Although, treatment of lung cancer has improved in recent years, the majority of patients will still succumb to this disease. Improving our understanding of the tumor microenvironment will increase our ability to reactivate the natural defense mechanisms that are silenced in patients with malignant tumors. The goal of this work is to learn how to harness lipids to improve tumor immunity and sensitivity to currently available cancer therapies.

PI_NAMEs: SIMMONS, GLENN EDWARD (contact)

PROGRAM_OFFICER_NAME: WALI, ANIL

PROJECT_TERMS: 3-Dimensional;advanced disease;Advisory Committees;anti-CTLA4;anti-PD-1;anti-tumor immune response;biobank;Biological Response Modifiers;Biology;bioprinting;Blood specimen;Cancer Biology;Cancer Etiology;Cancer Patient;cancer therapy;career;career development;Cell secretion;cell type;Cells;Cessation of life;cytokine;Cytotoxic T-Lymphocytes;Data;Defense Mechanisms;desaturase;design;Development;Disease;Environment;Enzymes;extracellular;Failure;Fibroblasts;Genetic;Goals;HMGB1 gene;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;Immunity;immunogenicity;Immunologics;Immunology procedure;immunoregulation;Immunosuppression;Immunotherapy;improved;Inflammation;inhibitor;Innate Immune Response;innovation;insight;Interleukin-10;Learning;Ligands;Lipid Biochemistry;lipidomics;Lipids;Lung;Lung Adenocarcinoma;lung cancer cell;Lung Diseases;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Mediating;Melanoma;Mentors;Minnesota;Modeling;Molecular;Molecular Biology;Monounsaturated Fatty Acids;mortality;Natural Immunity;Non-Small-Cell Lung Carcinoma;Normal tissue morphology;Oncology;Patient Care;Patients;Pattern;pharmacologic;Population;prevent;programs;receptor;Refractory Disease;Regulation;Regulatory T-Lymphocyte;Research;Research Personnel;response;Role;Scientist;Serum;Signal Transduction;SIRT1 gene;skills;success;Testing;Therapeutic;Tissues;Training;Transforming Growth Factor beta;Translating;translational cancer research;translational scientist;treatment response;tumor;Tumor Immunity;tumor microenvironment;tumor-immune system interactions;United States;Universities;Vascularization;Work

PROJECT_TITLE: Regulation of the innate immune response in the tumor microenvironment of lung adenocarcinoma

STUDY_SECTION: NCI

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Infectious Diseases;Mental Health;Pediatric;Prevention;Social Determinants of Health;Violence Research

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: The COVID-19 pandemic has created numerous challenges and stressors for family functioning that have increased rates of domestic violence and child maltreatment in the United States and across the Globe. Accordingly, developmental scientists, clinicians, and public policy advocates have underscored the public health significance of advancing an understanding of the lasting impact of COVID-19 on family functioning. The current application offers time-sensitive opportunity to examine how the disruptions associated with through building upon the aims of a multi-method, longitudinal study of families in a current R01 project through examining how COVID-19 modifies associations between interparental hostility and harsh parenting in families with young children and how parental self-regulation may underlie these processes.

PI_NAMEs: DAVIES, PATRICK T;STURGE-APPLE, MELISSA L (contact)

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TERMS: Acute;Address;Advocate;Catalogs;Characteristics;Child;Child Abuse and Neglect;Child Rearing;Clinical;Cognitive;Conflict (Psychology);Coronavirus;COVID-19;COVID-19 impact;COVID-19 pandemic;Data;Data Collection;Data Set;Development;Discipline;Distress;Domestic Violence;Economics;evidence base;Family;Family dynamics;Family Relationship;Family Study;Fathers;Health;Home;Hostility;Hurricane;Individual;individual variation;infection rate;Informal Social Control;informant;Job loss;Knowledge;longitudinal design;Longitudinal Studies;Mediating;Mental Health;Methods;Modeling;Mothers;Nature;Neurobiology;New York;pandemic disease;Parents;Personal Satisfaction;Phase;phase 2 study;physical conditioning;Prevention program;Process;protective factors;Public Health;Public Policy;Quasi-experiment;Reporting;Research;Risk;Risk Factors;school closure;school disruption;Scientist;Social Functioning;Source;Stress;stressor;System;Systems Theory;Testing;Time;United States;Virus;Work

PROJECT_TITLE: Interparental Conflict and Parenting in the Context of COVID-19

STUDY_SECTION: SPIP

STUDY_SECTION_NAME: Social Psychology, Personality and Interpersonal Processes Study Section[SPIP]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Neurosciences;Physical Injury - Accidents and Adverse Effects;Physical Rehabilitation;Rehabilitation;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_DEPT: PHYSICAL MEDICINE & REHAB

PHR: Project Narrative Traumatic brain injury (TBI) is a significant health care issue that affects 10 million individuals each year throughout the world and about 2.8 million in United States for whom there are limited treatment options. While numerous invasive therapies have been evaluated, one non-invasive approach that has clinical relevance is environmental enrichment (EE), which is a therapeutic regimen that we have refined over the course of the parent grant to mimic clinical rehabilitation and has been shown to provide significant benefits relative to non- enriched housing. While EE is being optimized as a potential model of neurorehabilitation, additional empirical research is essential to learn more about its capabilities and limitations that ultimately strengthen its validity and applicability, and thus the goal of this renewal is to evaluate EE long-term, the effects of refresher rehabilitation, and bridge therapies that robustly expand on the parent grant successes that will fill gaps and expand our understanding of behavioral outcomes and mechanisms after TBI.

PI_NAMEs: KLINE, ANTHONY E. (contact)

PROGRAM_OFFICER_NAME: AWWAD, HIBAH OMAR

PROJECT_TITLE: Optimizing Environmental Enrichment to Model Preclinical Neurorehabilitation

STUDY_SECTION: BINP

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Clinical Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Mental Illness;Prevention;Primary Health Care;Social Determinants of Health;Suicide;Suicide Prevention;Violence Research

ORG_CITY: Oakland

ORG_NAME: KAISER FOUNDATION RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE Suicide is one of the main drivers of increased mortality attributed to “diseases of despair” in the U.S. Suicide risk prediction algorithms have potential to vastly improve identification of individuals at high risk of suicide, but there is very little evidence to guide routine use of this powerful technology in primary care. Project deliverables will include clinical decision support tools designed to support use of suicide risk predictive analytics in primary care, that can be potentially scaled nationwide, and lay a foundation for future evaluation of the effectiveness of implementation for preventing suicide attempts and deaths.

PI_NAMEs: ANGERHOFER, JULIE ELISSA (contact)

PROGRAM_OFFICER_NAME: LUSHIN, VICTOR

PROJECT_TERMS: Address;Adolescent;Adolescent and Young Adult;adolescent patient;Adult;Age;Algorithms;Behavioral;career;Caring;Cause of Death;Cessation of life;Clinic;Clinical;clinical care;clinical decision support;clinical decision-making;clinical implementation;clinical practice;Collaborations;Communication;cost;COVID-19;COVID-19 pandemic;design;Discover, Design, Build, and Test Framework;Disease;Documentation;effectiveness evaluation;Effectiveness of Interventions;Emergency department visit;emotional distress;ethnic disparity;follow-up;Foundations;Future;future implementation;Health;Health Personnel;Healthcare;Healthcare Systems;high risk;human centered design;implementation efforts;implementation evaluation;improved;Individual;inpatient psychiatric treatment;medical specialties;Mental Health;Methods;model development;Modeling;mortality;multidisciplinary;Outcome;outreach;Pathway interactions;Patient-Centered Care;Patients;pilot test;Population;Predictive Analytics;predictive modeling;prevention practice;Primary Care;primary care clinic;primary care clinician;primary care patient;primary care provider;Process;programs;prototype;Provider;Qualitative Methods;racial disparity;Recovery;reducing suicide;Reporting;Research;Research Personnel;Risk;Risk Assessment;risk mitigation;risk prediction model;Safety;social stigma;sociodemographics;Statistical Data Interpretation;Statistical Methods;suicidal;suicidal behavior;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;Suicide prevention;support tools;Surveys;Technology;Testing;Time;tool;United States Department of Veterans Affairs;usability;Veterans;virtual;Visit;Washington;Work

PROJECT_TITLE: Pilot Testing Implementation of Suicide Risk Prediction Algorithms to Support Suicide Prevention in Primary Care


ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE Lung cancer is the leading cause of cancer deaths worldwide, accounting for ~130,000 lives annually in the US alone. We have generated data from a large cohort of lung cancer patients showing that neutrophils inversely correlate with CD4+ and CD8+ lymphocyte content within lung tumors. The purpose of this project is to demonstrate that tumor-associated neutrophils limit the ability of T cells to infiltrate into the malignant portions of tumors. Successful completion of the proposed studies should identify a therapeutic strategy with which to improve T cell infiltration into cancers that would improve response rates to immune based therapies.

PI_NAMEs: HOUGHTON, A MCGARRY (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Accounting;Activated Lymphocyte;anti-PD-1;anti-PD-L1;anti-PD-L1 therapy;Antibody Therapy;Beds;Biological Assay;Bone Marrow;Cancer Etiology;Cancer Patient;Cathepsin G;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell surface;cell type;Cells;Cessation of life;checkpoint therapy;chemokine;chemokine receptor;Chemotaxis;Clinical;Clinical Trials;cohort;CXC chemokine receptor 3;CXCL10 gene;CXCL9 gene;CXCR3 gene;cytokine;Cytoplasmic Granules;Data;Dendritic Cells;Event;exhaust;Failure;Feedback;Fluorescent in Situ Hybridization;Genes;Human;Immune;immune checkpoint;Immune checkpoint inhibitor;Immune response;Immunohistochemistry;Immunotherapy;improved;In Vitro;in vivo;Infiltration;inhibitor;Interferon Type II;Leukocyte Elastase;Link;Lung Neoplasms;Lymphocyte;Lymphocyte Function;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Mediating;MMP8 gene;MMP9 gene;Modeling;mouse model;Mus;mutant;Myelogenous;Myeloid-derived suppressor cells;neoplastic cell;neutrophil;Neutrophil Collagenase;Neutrophil Infiltration;Non-Small-Cell Lung Carcinoma;novel;Outcome;PD-1/PD-L1;Peptide Hydrolases;Predictive Factor;Process;Production;Property;Protease Inhibitor;Proteinase 3;proteinase In;Proteins;recruit;Reporting;response;Signal Transduction;Site;Source;success;Surface;System;T cell infiltration;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;Thinking;Treatment outcome;treatment response;tumor;tumor microenvironment;Tumor-associated macrophages;Work

PROJECT_TITLE: Neutrophil derived proteinases abolish the IFNG signature in NSCLC

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BTC-Q(80)S]


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: Aurora

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative Nanomedicine is a promising field in drug delivery and imaging. This proposal aims to improve blood compatibility of nanoparticles by understanding and inhibiting the pathways that are responsible for immune response towards nanoparticles and side effects in patients.

PI_NAMEs: SIMBERG, DMITRI  (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: Acute;Alternative Complement Pathway;Autoimmune Diseases;Binding;Biological Assay;biomaterial compatibility;Blood;Canis familiaris;Cell membrane;Chimeric Proteins;Clinical;clinical development;Clinical Trials;cohort;Companions;Complement;Complement 3d Receptors;Complement Activation;Complement Inactivators;complement system;crosslink;cytokine;Dangerousness;Data;Deposition;design;Development;Disease remission;Dose;Doxorubicin Hydrochloride Liposome;Drug Delivery Systems;efficacy study;Electron Microscopy;experimental study;Family suidae;ferumoxytol;Funding;Goals;hemocompatibility;high throughput screening;Human;Image;imaging system;Immobilization;Immune;Immune response;immunoreaction;improved;In Vitro;in vivo;Incubated;Infection;Infusion procedures;inhibitor;Intervention;Intravenous;irinotecan;iron oxide;iron oxide nanoparticle;Leukocytes;Liposomes;Literature;Measurement;Measures;molecular imaging;Monitor;Mus;nano;nanodrug;nanoengineering;nanoformulation;nanoGold;nanomaterials;nanomedicine;nanoparticle;nanoparticulate;nanosized;nanotechnology platform;novel;novel strategies;Pathway interactions;Patients;Phagocytes;Pharmaceutical Preparations;Phase;Plasma;pre-clinical;prevent;Prevention strategy;Proteins;Proteomics;Reaction;Research;response;Role;Safety;Serum;side effect;Sterically Stabilized Liposome;superparamagnetism;Surface;Sushi Domain;System;technological innovation;Testing;uptake

PROJECT_TITLE: The Alternative Complement Pathway and Hemocompatibility of Nanosurfaces

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


ADMINISTERING_IC: OD

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

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

ORG_CITY: ATLANTA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: EMORY UNIVERSITY

PHR: PROJECT NARRATIVE HIV/AIDS is a global concern. With 38 million people currently estimated to be living with HIV worldwide, it is imperative to develop better treatments and interventions to prevent and/or cure HIV infection. This annual symposium will facilitate and promote exchange of new research findings, scientific approaches and perspectives, and foster new collaborations among HIV/AIDS investigators whose research includes studies in nonhuman primates (NHPs).

PI_NAMEs: JOHNSON, R. PAUL (contact);MORRISON, JOHN H;RAPPAPORT, JAY

PROGRAM_OFFICER_NAME: ZOU, SIGE

PROJECT_TERMS: Acceleration;Acquired Immunodeficiency Syndrome;Address;Adult;AIDS Vaccines;Antibodies;antiretroviral therapy;Applications Grants;Budgets;California;Child;Clinic;Clinical;co-infection;Collaborations;Communicable Diseases;cost;COVID-19;COVID-19 pandemic;COVID-19 pathogenesis;COVID-19 treatment;COVID-19 vaccine;Development;disability;Disease;Emerging Technologies;experience;falls;Fees;Fostering;Funding;Future;Generations;Genomics;global health;Grant;Health;HIV;HIV Infections;HIV vaccine;HIV Vaccine Trials Network;HIV/AIDS;Human;Hybrids;immunodeficiency;Immunology;Individual;International;Intervention;Journals;Knowledge;Life;Link;Logistics;Medical;meetings;Mentors;Mission;Modeling;neutralizing antibody;NIH Vaccine Research Center;nonhuman primate;novel therapeutics;Oral;Oregon;originality;Participant;Pathogenesis;Pennsylvania;Persons;posters;prevent;Prevention;Preventive vaccine;Primates;programs;Publishing;Research;Research Personnel;response;Role;Rotation;Scientific Advances and Accomplishments;Scientist;SIV;symposium;Technology;Testing;therapy design;Translations;transmission process;United States National Institutes of Health;Vaccines;Virus Diseases;Writing

PROJECT_TITLE: Annual Symposium on Nonhuman Primates


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_CITY: PISCATAWAY

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

PHR: RELEVANCE Hypoxia (O2 deprivation) plays a central role in a diverse array of human diseases, including ischemic stroke, myocardial infarction, traumatic brain injury, spinal cord injury, pulmonary hypertension, Cerebral Palsy, COVID-19, and cancer. Our tissues respond to hypoxia by employing a conserved hypoxia response pathway, yet we have a poor understanding of how this response combats hypoxic damage. It is critical to identify and functionally characterize key targets of this pathway in order to develop novel applications for the treatment and prevention of disorders and diseases that involve hypoxia as part of their etiology.

PI_NAMEs: RONGO, CHRISTOPHER G (contact)

PROGRAM_OFFICER_NAME: BLATCH, SYDELLA ANNE

PROJECT_TERMS: Aerobic;Antioxidants;Autophagocytosis;Binding;Biological;Biological Models;Caenorhabditis elegans;Cells;Cerebral Palsy;ChIP-seq;combat;COVID-19;CRISPR/Cas technology;deprivation;Disease;disorder prevention;Drug Metabolic Detoxication;Enhancers;Environment;Enzymes;Etiology;Excision;experimental study;Gene Expression;Generations;Genes;Genetic;genetic analysis;Genetic Enhancer Element;Genetic Models;Genetic Transcription;Gluconeogenesis;human disease;Hydroxylation;Hypoxia;Hypoxia Inducible Factor;hypoxia inducible factor 1;Impairment;in vivo;Individual;inorganic phosphate;Ischemic Stroke;Malignant Neoplasms;Metabolic;Metabolism;metabolomics;Mitochondria;model organism;Muscle;mutant;Mutation;Myocardial Infarction;NADP;Nerve Degeneration;Neuronal Hypoxia;Neurons;normoxia;novel;Organism;Orthologous Gene;Oxidative Phosphorylation;Oxidative Stress;Pathway interactions;Pentosephosphate Pathway;Phase;Play;Procollagen-Proline Dioxygenase;Production;Proline;promoter;protective pathway;Proteins;Proteolysis;Pulmonary Hypertension;Reactive Oxygen Species;receptor;Reduced Glutathione;Regulation;Reporter;Reproducibility;Resistance;response;Role;Side;Solid Neoplasm;Source;spinal cord and brain injury;stem cell niche;Testing;therapeutic target;tissue culture;Tissues;Transcriptional Regulation;transcriptome;transcriptome sequencing;Traumatic Brain Injury;ubiquitin ligase;Warburg Effect

PROJECT_TITLE: Genetic Analysis of Neuronal Hypoxia Resistance

STUDY_SECTION: NOMD

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