ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Data Science;Health Services;Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety;Prevention

ORG_CITY: ROCHESTER

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: ROCHESTER INSTITUTE OF TECHNOLOGY

PHR: Project Summary/Abstract In-home monitoring technologies have the potential to transform the healthcare system by enabling the transition from reactive care to proactive and preventive care. This study will leverage a highly innovative technology for cardiovascular in-home daily monitoring; the fully integrated toilet seat (FIT). A multidisciplinary research team, comprised of engineers, physicians, advanced practice providers, data scientists, biostatisticians, designers, and software developers, will advance an automated system that provides health care providers with early warning of patient deterioration through an in-home clinical trial of heart failure patients.

PI_NAMEs: WANG, LINWEI  (contact);ZAREBA, WOJCIECH

PROGRAM_OFFICER_NAME: MCNAMARA, KAREN MARIE

PROJECT_TERMS: Address;Admission activity;Adverse event;American;Architecture;Awareness;Behavior;Blood;Blood Pressure;Cardiac Output;Cardiovascular Diseases;Cardiovascular system;Caring;Cause of Death;Cessation of life;Clinical;Clinical Data;Clinical Trials;clinically relevant;cohort;Collaborations;Computer software;Computerized Medical Record;Control Groups;cost;Custom;Data;data integration;Data Scientist;Data Set;data streams;data visualization;Deterioration;Early Intervention;Electrocardiogram;Engineering;Ensure;Generations;Habits;Health Personnel;Healthcare Systems;Heart failure;Heart Rate;heart rate variability;Home;Hospitalization;hospitalization rates;Hospitals;improved;innovative technologies;Instruction;Interdisciplinary Study;Intervention;Intervention Studies;Interview;Label;Lead;Learning;Length of Stay;Machine Learning;machine learning model;Measurement;Measures;model development;Modeling;Monitor;multidimensional data;Myocardium;Notification;novel;Patient Compliance;Patients;Pattern;Pharmaceutical Preparations;Physicians;Physiological;predictive modeling;Predictive Value;Preventive care;Probability;Provider;provider intervention;Quality of life;recurrent neural network;remote patient monitoring;Research;Risk;Slide;success;System;Techniques;Technology;Telephone;Testing;Time;Training;trend;Update;Visit;Weight;Work

PROJECT_TITLE: Inconspicuous Daily Monitoring to Reduce Heart Failure Hospitalizations

STUDY_SECTION: BCHI

STUDY_SECTION_NAME: Biomedical Computing and Health Informatics Study Section[BCHI]


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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

ORG_CITY: BIRMINGHAM

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PATHOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PROJECT NARRATIVE Diarrheal pathogens are the cause of over 1.5 million deaths globally each year, mostly affecting children in underdeveloped countries. Barrier maintenance and host defense against diarrheal pathogens requires the complex interplay of both immune cells and intestinal epithelial cells, but how these cell types cooperate to eradicate pathogens is largely unknown. This proposal seeks to eclucidate the mechanisms by which IFN acts on intestinal epithelial cells to recruit and sustain local IL-22 delivery from pathogen-specific CD4+ T cells in the setting of intestinal infection and how this process can be manipulated for therapeutic benefit in the treatment of diarrheal illness.

PI_NAMEs: WILSON, CHRISTOPHER GARRETT (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: Adoptive Transfer;Affect;anti-microbial peptide;Antigen Presentation;antigen-specific T cells;antimicrobial;Automobile Driving;base;CD4 Positive T Lymphocytes;Cell Communication;cell motility;cell type;Cells;Cessation of life;Charge;chemokine;Child;Citrobacter rodentium;Collaborations;Colon;colonic crypt;Complex;cytokine;Cytoprotection;Developing Countries;Diarrhea;diarrheal disease;Disease;effector T cell;Engineering;enteric infection;enteric pathogen;Enterocytes;enteropathogenic Escherichia coli;Epithelial Cells;Epithelium;Escherichia coli EHEC;Escherichia coli Infections;Etiology;Family;Genes;Genetic Transcription;Goals;Goblet Cells;Host Defense;human model;Hyperplasia;Immune;Immune response;Immunology;In Situ;Infant;Infection;Infectious colitis;Inflammation Mediators;Inflammatory Bowel Diseases;innovation;Innovative Therapy;insight;interleukin-22;intestinal barrier;intestinal crypt;intestinal epithelium;Intestines;Knowledge;Lead;LGR5 gene;Ligands;Lymphocytic choriomeningitis virus;Maintenance;Mediating;Metabolic;MHC Class II Genes;Modeling;Molecular;mortality;Mucous body substance;Mucous Membrane;Mus;new therapeutic target;novel;novel therapeutics;Oranges;pathogen;Phase;Predisposition;Prevention;Process;programs;Proteins;receptor;recruit;Reporting;Research;response;restraint;Role;Signal Transduction;single-cell RNA sequencing;STAT3 gene;stem cells;Surface;T cell regulation;T cell response;T cell therapy;T-Lymphocyte;TCR Activation;Testing;Therapeutic;Training;Transgenic Organisms;Up-Regulation

PROJECT_TITLE: Coordination of T cell-derived signals in intestinal epithelial barrier defense


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Biotechnology;Congenital Structural Anomalies;Eye Disease and Disorders of Vision;Genetics;Pediatric

ORG_CITY: Newark

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF DELAWARE

ORG_STATE: DE

PHR: Project Narrative Cataracts are the leading cause of blindness worldwide. Therefore, it is essential to understand the molecular mechanisms that contribute to the formation and maintenance of lens transparency. The proposed research will result in the characterization of novel pathways in lens development, homeostasis and pathogenesis and will continue development of a publicly available web-based interactive tool – for both clinicians and scientists – that facilitates prediction and prioritization of genes/pathways to further accelerate cataract gene discovery.

PI_NAMEs: LACHKE, SALIL  (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: 3' Untranslated Regions;Acceleration;Address;aged;aging population;American;Animal Model;Antibodies;Binding;Binding Sites;Bioinformatics;bioinformatics resource;Biological Assay;Biology;Birth;Blindness;Cataract;Cellular Assay;childhood cataract;CISH gene;Co-Immunoprecipitations;combinatorial;comparative;Complex;conditional knockout;crosslink;crosslinking and immunoprecipitation sequencing;Crystalline Lens;Data;Defect;Development;Disease;dosage;E-Cadherin;early childhood;early onset;Embryo;Ensure;Etiology;Exhibits;Eye;Fertilization;Funding;gene discovery;Gene Expression;Gene Expression Regulation;gene regulatory network;Genes;Genetic;Genetic Transcription;Genomics;Goals;Histology;Homeostasis;human model;Immunoprecipitation;Impairment;innovation;insight;interactive tool;Investigation;Knock-out;Knockout Mice;Knowledge;lens;Lens development;lens transparency;Light;Link;LoxP-flanked allele;Maintenance;Mediating;Messenger RNA;Microphthalmos;Molecular;Morphology;mouse model;mRNA Precursor;mRNA Stability;mRNA Translation;Mus;Nature;novel;online resource;Online Systems;Organogenesis;Pathogenesis;Pathology;Pathway interactions;Post-Transcriptional Regulation;posttranscriptional;Process;Proteins;Proteome;Proteomics;Regulation;Research;Retina;RNA;RNA Splicing;RNA-Binding Proteins;Role;Scanning Electron Microscopy;Scientist;Signal Transduction;System;Testing;Tissues;tool;transcription factor;transcriptome;transcriptome sequencing;Translations;Vision

PROJECT_TITLE: Post transcriptional control of gene expression in the lens

STUDY_SECTION: BVS

STUDY_SECTION_NAME: Biology of the Visual System Study Section[BVS]


ADMINISTERING_IC: AI

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: ATLANTA

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: This over-arching goal of this T32 renewal grant is to provide support for pre-doctoral students at Emory University in order to help deliver the next generation of scientists needed to continue the fight against bacterial and viral pathogens. The training faculty work on a wide range of projects dealing with anti-infective resistance and drug or vaccine discovery and development with respect to major microbial pathogens and their associated diseases that impact public health, including tuberculosis, HIV/AIDS, hepatitis, influenza, sexually transmitted infections, pneumonia, meningitis, nosocomial and skin/soft tissue infections. By our continued training of students in the foundations of antimicrobial resistance, vaccinology and drug discovery the above-stated goal will be realized.

PI_NAMEs: CONN, GRAEME L;SHAFER, WILLIAM MAURICE (contact)

PROGRAM_OFFICER_NAME: BROWN, LILIANA L

PROJECT_TITLE: Antimicrobial Resistance and Therapeutic Discovery Training Program

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: BALTIMORE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: A novel pro-drug form of the human proteasome named Rapaprotin has been identified from the rapamycin-inspired macrocycle library. Rapaprotin showed selectivity towards cancer cells over normal cells and synergy with existing proteasome-targeting drugs. Rapaprotin and its analogs have potential to become new chemical probes of the proteasome and promising leads for developing novel anticancer drugs.

PI_NAMEs: LIU, JUN O. (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Adverse effects;analog;Animal Model;anti-cancer;Antineoplastic Agents;Apoptotic;Archaea;Bacteria;Binding;Binding Sites;Biological Availability;Bortezomib;cancer cell;cancer type;Cell Line;Cell Physiology;Cells;Chemicals;Clinic;combinatorial;Complex;CRISPR screen;Cryoelectron Microscopy;design;Development;Disease;Drug Kinetics;Drug resistance;Drug Targeting;Eukaryota;Exhibits;Garbage;Genetic Transcription;genome-wide;Human;Hydrolysis;Immunoglobulins;Immunosuppressive Agents;improved;in vivo;Induction of Apoptosis;inhibitor;insight;Lead;Libraries;Lymphoma;Malignant Neoplasms;Mediating;Mediator;multicatalytic endopeptidase complex;Multiple Myeloma;Names;Normal Cell;novel;novel anticancer drug;Patients;Penetration;Peptide Hydrolases;Peptide Library;Periodicity;Peripheral Nervous System Diseases;Pharmaceutical Chemistry;Pharmaceutical Preparations;Pharmacology;Photoaffinity Labels;Plasma Cell Neoplasm;Play;potential biomarker;predictive marker;Prodrugs;prolyl oligopeptidase;Property;Proteasome Inhibition;Proteasome Inhibitor;Proteins;proteostasis;refractory cancer;Regulation;Resistance;Resolution;Role;Route;Safety;Signal Transduction;Sirolimus;Site;Structure;Structure-Activity Relationship;success;synergism;Tacrolimus Binding Proteins;Therapeutic;tool;Toxic effect;tumor;Work

PROJECT_TITLE: Characterization of A Novel Proteasome Inhibitor

STUDY_SECTION: SBCB

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Rare Diseases

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: TITLE: Venous Malformations (VM): murine model to identify therapies to target aberrant venous development PROJECT NARRATIVE: Venous malformation (VM) appear in young children, are severely disfiguring and cause chronic pain and increased risk of pulmonary embolism. We use patient-derived in vivo and 3D models to identify signaling molecules implicated in the formation of abnormal blood vessels in VM patients. Our findings will be fundamental for the development of novel targeted therapeutic strategies for the treatment of patients affected by VM or other vascular anomalies with dilated vasculature.

PI_NAMEs: BOSCOLO, ELISA  (contact)

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: 2-tyrosine;3-Dimensional;Affect;angiogenesis;Automobile Driving;Binding;Birth;Blood Vessels;Cell Line;cell motility;Cell Proliferation;Cell Separation;Cells;cellular engineering;Chemicals;Child;Chronic;chronic pain;Clinical Management;Clinical Trials;cytokine;Data;Development;Disease;Drug Screening;Endothelial Cells;Endothelium;Etiology;Excision;Functional disorder;Funding;Future;gain of function mutation;Genetic;Goals;Growth;Human;Hyperactivity;Impairment;In Vitro;in vivo;inhibitor;insight;Intervention;knock-down;Knowledge;Lesion;Maintenance;malformation;Mediator;migration;Molecular;molecular targeted therapies;Morbidity - disease rate;Morphogenesis;mouse model;mTOR Inhibitor;Mus;mutant;Mutation;new therapeutic target;novel;Operative Surgical Procedures;Pain;Pathogenicity;Pathologic;Patients;pharmacologic;Phosphotransferases;Physiological;PIK3CG gene;prevent;programs;Protein Kinase;Protein Tyrosine Kinase;Proto-Oncogene Proteins c-akt;Publishing;Pulmonary Embolism;Receptor Protein-Tyrosine Kinases;recruit;Reporting;Research;rho GTP-Binding Proteins;Risk;Role;Sclerotherapy;Seminal;Signal Transduction;Signaling Molecule;Sirolimus;Subcutaneous Injections;symptom management;System;targeted treatment;Testing;three-dimensional modeling;Time;Tissues;treatment strategy;Umbilical vein;vascular abnormality;Veins;Venous;Venous Malformation;Xenograft procedure

PROJECT_TITLE: Venous Malformations (VM): A Murine Mdoel to Identify Therapies to Target Aberrant Venous Development

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Eczema / Atopic Dermatitis;Infectious Diseases;Microbiome;Prevention

ORG_CITY: PHILADELPHIA

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE The skin is colonized by microbial communities, but their role in the barrier function of the skin is not well- defined. The proposed research will illuminate the molecules produced by beneficial skin microbes, their impact on the skin, and their therapeutic potential for treating inflammatory and infectious skin diseases. Findings from these studies will provide insight into fundamental roles of our endogenous microbiota while advancing targets for the treatment of skin disease.

PI_NAMEs: GRICE, ELIZABETH ANNE (contact);SUTTER, THOMAS R

PROGRAM_OFFICER_NAME: UNDALE, ANITA H

PROJECT_TERMS: Adhesions;Agonist;anti-microbial peptide;Antibiotics;antimicrobial;Aryl Hydrocarbon Receptor;aryl hydrocarbon receptor ligand;Atopic Dermatitis;Bacterial Infections;Biochemical;Biology;Calcipotriene;Cells;Chronic;Collaborations;commensal bacteria;Cutaneous;Data;Defect;Disease;dysbiosis;efficacy evaluation;Ensure;Epithelium;Flowers;Functional disorder;Genetic Transcription;Germ-Free;Goals;Homeostasis;host microbiota;Human;improved;In Vitro;in vivo;Infection;Infection prevention;Infectious Skin Diseases;Inflammation;Inflammatory;Injury;injury recovery;Innate Immune Response;insight;keratinocyte;Ligands;Mediating;Mediator;Microbe;microbial;microbial colonization;microbial community;microbiota;Modeling;Molecular;mouse model;multiple omics;Mus;Names;novel;Ovalbumin;pathogen;Pathology;Pathway interactions;Pattern recognition receptor;Permeability;Pharmacodynamics;Poison;Predisposition;prevent;Prevention;receptor;Receptor Activation;Receptor Signaling;Regulation;Relapse;repaired;Research;Role;safety assessment;Skin;skin barrier;skin disorder;skin lesion;Staphylococcus aureus;Staphylococcus aureus infection;Symbiosis;Testing;Therapeutic;Tight Junctions;Tissues;Tryptophan;Xenobiotics

PROJECT_TITLE: Microbial regulation of the keratinocyte AHR


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Headaches;Hearing Loss;Mental Health;Migraine;Neurosciences;Pain Research

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS EYE AND EAR INFIRMARY

ORG_STATE: MA

PHR: Project Narrative For many individuals with sensory impairment or neurodevelopmental disorders, moderate stimuli can be perceived as overwhelmingly intense. This work will identify neurobiological signatures of hyperacusis, an auditory hypersensitivity disorder that often accompanies migraine, Autism, Fragile X syndrome and sensorineural hearing loss. This work would identify neural circuit mechanisms for hyperacusis and open new long-term therapeutic avenues for a common neurological disorder that has no widely accepted treatment.

PI_NAMEs: POLLEY, DANIEL B. (contact)

PROGRAM_OFFICER_NAME: MILLER, ROGER

PROJECT_TERMS: Acoustic Stimulation;Acoustics;Amygdaloid structure;Anxiety;Anxiety Disorders;Auditory;Auditory area;auditory pathway;Auditory Perception;auditory thalamus;autism spectrum disorder;Axon;Behavior;behavior test;Behavioral;Behavioral Assay;Biological;Brain Stem;Bypass;Calcium;cell type;Cells;Chronic;Chronology;comorbidity;Compensation;Correlation Studies;density;Disease;Dorsal;Ear;Earache;Electrophysiology (science);Equilibrium;excitatory neuron;Exhibits;experimental study;Fiber;forging;Fragile X Syndrome;Freezing;Friends;Fright;Frustration;Growth;Head;Health;Hearing;hearing impairment;Hearing problem;High-Frequency Hearing Loss;hippocampal pyramidal neuron;Hyperactivity;Hyperacusis;Hypersensitivity;Image;Individual;Inferior Colliculus;inhibitory neuron;insight;Lateral;Letters;Link;Loudness;Loudness Perception;Measures;Mediating;Membrane;Methods;Migraine;millisecond;Modeling;Modernization;Mood Disorders;mouse model;Mus;Nervous System Disorder;neural;neural circuit;neural correlate;Neurobiology;Neurodevelopmental Disorder;Neurons;Neurosciences;Noise;noise exposure;Noise-Induced Hearing Loss;normal hearing;novel therapeutic intervention;Opsin;optogenetics;Pain;Parvalbumins;Pathology;Pathway interactions;Perception;Persons;Phenotype;Photometry;Preparation;Process;Reporting;Resolution;Sensorineural Hearing Loss;Sensory;Sensory impairment;social;sound;Stimulus;Stress;Structure;System;Testing;Therapeutic;Tinnitus;tool;two-photon;Work

PROJECT_TITLE: Activity-Dependent Influences on Auditory Circuits

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: ES

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: CHICAGO

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The proposed project aims to create and maintain a diverse workforce in the environmental health sciences through the creation of an innovative program - Chicago UP on EHS - for underrepresented undergraduates by leveraging the robust scientific, educational, and mentoring infrastructure offered by CACHET. Through innovative partnerships with CACHET members, didactic instruction/preparation, and the pilot projects program, underrepresented students will have mentored research experiences and exposure to exciting and impactful projects that by-in-large aim to mitigate environmental health disparities in Chicago.

PI_NAMEs: AHSAN, HABIBUL ;ASCHEBROOK-KILFOY, BRISEIS A (contact)

PROGRAM_OFFICER_NAME: HUMBLE, MICHAEL C

PROJECT_TERMS: Address;Air;Area;biobank;Biological;Biological Assay;Biological Markers;Biomedical Research;career;career development;Chicago;Clinic;Communication;Communities;community based participatory research;community engagement;community partners;Complement;Core Facility;cultural competence;curriculum development;Dedications;Device or Instrument Development;Disease;Disease Outcome;disorder risk;Disparity;disparity reduction;Diverse Workforce;Economics;Education;Educational Activities;Ensure;Environment;Environmental Epidemiology;Environmental Exposure;Environmental Health;environmental health disparity;environmental justice;Equipment;ethnic health disparity;experience;Exposure to;Faculty;Focus Groups;Frontline worker;Funding;Genetic;Genomics;Goals;hands on research;Health;health inequalities;human disease;Illinois;Individual;Infrastructure;innovation;insight;Institution;Instruction;Knowledge;Laboratories;Leadership;Learning;Maternal and Child Health;Medical;member;Mentors;metabolomics;Metals;microbiome;minority communities;Mission;Molecular;multidisciplinary;Outcome;outreach;Pesticides;Pilot Projects;Population;population health;Positioning Attribute;Precision Health;Preparation;programs;prospective;Protocols documentation;Publications;racial health disparity;recruit;recruitment science;Research;Research Activity;Research Design;Research Methodology;Research Personnel;Research Project Grants;Research Training;Resources;Scientist;Side;skill acquisition;social;Specimen Handling;statistics;Structure;Students;success;support network;System;Thinking;Training;training opportunity;Training Programs;Training Support;Translating;undergraduate research experience;undergraduate student;Underrepresented Students;United States National Institutes of Health;Universities;Work;Workforce Development

PROJECT_TITLE: Chicago UP on the Environmental Health Sciences


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

ORG_CITY: RONDEBOSCH

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: UNIVERSITY OF CAPE TOWN

PHR: Project Narrative The aim of this research is to identify new drug candidates with novel modes of action for the treatment of malaria. The addition of new chemical matter and novel drug targets to the malaria drug development pipeline is an essential component of the global effort to combat drug resistance, eradicate malaria and improve health and quality of life in the developing world.

PI_NAMEs: CHIBALE, KELLY  (contact);FERRINS, LORI ;WILLSON, TIMOTHY M

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: Accounting;Affect;Affinity;African;Anti-malarials;Artemisinins;asexual;Biological;Biological Assay;Blood;cancer therapy;Cause of Death;Cells;Cessation of life;Chemicals;Child;Clinical;Collaborations;combat;Combined Modality Therapy;Computer Assisted;Country;Data;Development;Disease;drug candidate;Drug Design;drug development;drug discovery;Drug Kinetics;drug metabolism;Drug resistance;Drug Targeting;Drug usage;Ensure;experimental study;Genetic;Genomics;Goals;Health;Human;human disease;humanized mouse;improved;in vivo;in vivo Model;Infection;inhibitor;insight;interest;kinase inhibitor;Knowledge;Lead;lead optimization;Libraries;Life Cycle Stages;Malaria;malaria infection;marginalized community;Modeling;Modification;Monitor;mouse model;new therapeutic target;novel;novel therapeutics;Oral;Outcome;Parasites;Pharmaceutical Chemistry;Phenotype;Phosphotransferases;Plasmodium;Plasmodium falciparum;Proteins;Proteomics;Quality of life;Reagent;Recommendation;Reporting;Research;Resistance;Role;Safety;SCID Mice;screening;Series;structural genomics;Structure;success;Symptoms;Techniques;Testing;Toxic effect;Traditional Medicine;transmission process;Work;World Health Organization

PROJECT_TITLE: Repurposing kinase inhibitor chemotypes as antimalarials

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDM-W(50)R]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Breast Cancer;Cancer;Neurosciences;Orphan Drug;Ovarian Cancer;Radiation Oncology;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Women's Health Research

ORG_CITY: IRVINE

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: PROJECT NARRATIVE Cancer therapy-induced cognitive dysfunction (CRCI) or chemobrain is one of the major quality of life issue for cancer survivors. With over 16.9 million cancer survivors alive today, assessing long-term neurocognitive complications and effective clinical recourse is now considered the most important clinical criterion for evaluating therapeutic outcome. This proposal (in response to a chemobrain RFA, PAR-21-329) will delineate effectiveness of systemic injections of human neural stem cell-derived extracellular vesicles and miRNA-based mechanism of neurocognitive benefits using intact and cancer mouse models to ameliorate CRCI.

PI_NAMEs: ACHARYA, MUNJAL M (contact)

PROGRAM_OFFICER_NAME: ALTSHULER, RACHEL DINA

PROJECT_TERMS: Adjuvant Chemotherapy;Adriamycin PFS;Adult;Amygdaloid structure;Animals;Architecture;Behavioral;Brain;Cancer Model;Cancer Survivor;cancer therapy;candidate identification;Carboplatin;caregiver stress;Caring;chemobrain;chemoradiation;chemotherapy;Chemotherapy-Oncologic Procedure;Chronic;Cisplatin;Clinical;Clinical Data;Clinical Research;Cognitive deficits;cognitive function;cognitive task;coping;Cranial Irradiation;Cyclophosphamide;Data;density;Disease;Doxorubicin;Drug Kinetics;Effectiveness;effectiveness testing;Emotional;extracellular vesicles;Foundations;frontal lobe;Functional disorder;Gene Targeting;Genes;Growth;Hippocampus;Human;Impaired cognition;Impairment;improved;In Vitro;in vivo;Incidence;Inflammation;Inflammatory;Injections;Intravenous;irradiation;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;medial temporal lobe;Mediating;MicroRNAs;Modeling;Molecular;mouse model;Mus;nerve stem cell;Neurobiology;Neurocognitive;Neurodegenerative Disorders;neurogenesis;neuroinflammation;neuron loss;Neurons;neuroprotection;novel;novel therapeutic intervention;Paclitaxel;Pathologic;Patients;Performance;Play;pre-clinical;preclinical study;prevent;protein expression;Publishing;Quality of life;Radiation therapy;regenerative approach;Regimen;Research Design;response;Role;Safety;safety testing;Series;side effect;Signal Transduction;socioeconomics;stem cell exosomes;stem cells;Structure;Survivors;Synapses;Testing;Therapeutic;therapy design;therapy outcome;Toxic effect;Transgenic Mice;Translating;Transplantation;Treatment-Related Cancer;Validation;Veins;Vertebral column;Xenograft procedure

PROJECT_TITLE: Stem cell-derived exosomes to ameliorate chemobrain


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: COLLEGE STATION

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

ORG_STATE: TX

PHR: Project Narrative Exposure to cadmium (Cd) is hazardous to human health, and chronic exposure is a risk for carcinogenesis that includes prostate cancer. Our results suggested that Cd-exposure differently induced prostate malignancies (i.e.), Squamous cell carcinoma (SCC) in the transition zone (TZ) of the prostate, and poorly differentiated carcinoma (PDC) in the peripheral zone (PZ) of the prostate. Hence, the goal is to determine the pathobiology and molecular landscape of Cd-induced SCC's in both laboratory models and clinical specimens.

PI_NAMEs: DAMODARAN, CHENDIL  (contact)

PROGRAM_OFFICER_NAME: SHAUGHNESSY, DANIEL

PROJECT_TERMS: Anatomy;Apoptotic;Benign Prostatic Hypertrophy;Binding;Blood;Cadmium;Cancer Patient;carcinogenesis;Carcinogens;Carcinoma;Cells;Cerebellum;Chronic;Clinical;cohort;CRISPR/Cas technology;Development;Dose;Epidemiology;exposed human population;Exposure to;genetic approach;GLI gene;Goals;Health;Human;In Vitro;in vivo;inducible Cre;innovation;insight;Knockout Mice;Knowledge;Laboratories;Malignant - descriptor;Malignant neoplasm of prostate;Measures;Metals;Modeling;Molecular;molecular marker;mouse model;Mus;Oncogenic;overexpression;Patients;Pattern;Peripheral;pharmacologic;Plasma;pre-clinical;Prostate;Proteins;Regulation;Response Elements;Risk;Risk Factors;Role;Serum;SHH gene;Signal Transduction;smoothened signaling pathway;Specimen;spheroids;Squamous cell carcinoma;subcutaneous;Tamoxifen;Tissues;tool;transcription factor;tumor;Tumor Tissue;tumorigenesis;Urine;Xenograft procedure;Zinc Fingers

PROJECT_TITLE: Elucidating the molecular signaling of Cadmium Carcinogenesis

STUDY_SECTION: SIEE

STUDY_SECTION_NAME: Systemic Injury by Environmental Exposure[SIEE]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Neurosciences;Pediatric

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Project Narrative Imbalances in the relationship between neuronal and immune cells during development cause inflammatory cascades which drive neurodevelopmental disorders, including autism and schizophrenia. This proposal seeks to understand how an unexpected immune cell, the mast cell, is recruited to the developing brain and promotes the normal developmental trajectory of surrounding glia. Elucidating the mechanisms by which peripheral immune cells shape neurodevelopmental processes will strengthen our understanding of how inflammatory disturbances cause neurologic disease.

PI_NAMEs: BLANCHARD, ALEXA CIESINSKI (contact)

PROGRAM_OFFICER_NAME: GIRARDI, GUILLERMINA

PROJECT_TERMS: Address;Adolescent;Adult;Affect;Affective;Age;Attention;autism spectrum disorder;B-Lymphocytes;Behavior;Bioinformatics;blood-brain barrier permeabilization;Bone Marrow;Brain;brain cell;brain tissue;career;Cell Count;Cell Maintenance;Cell Proliferation;Cell Shape;Cells;Central Nervous System;Child;Childhood;Choroid;Chronic;Clinical;cognitive function;Communication;Complex;cytokine;Data;Development;Developmental Process;Diagnosis;Disease;Embryo;experimental study;Fostering;Foundations;Functional disorder;glial cell development;granulocyte;Growth Factor;Health;Helper-Inducer T-Lymphocyte;Heterogeneity;hippocampal fissure;Hippocampus;Histamine;Homeostasis;Immersion;Immune;immune cell infiltrate;immunogenic;Immunologist;Inflammation;Inflammation Mediators;Inflammatory;injured;Innate Immune System;insight;Invaded;lateral ventricle;Life;mast cell;mastocytosis;Mediator;Mentorship;Microglia;Molecular;Morphology;neonatal brain;Nervous System Disorder;neural;Neurodegenerative Disorders;neurodevelopment;Neurodevelopmental Disorder;neurogenesis;Neuroglia;Neuroimmune;Neurologic Deficit;Neurologist;neuron development;Neurons;novel;Pathology;Pattern;Pediatric Neurology;Perinatal;perinatal period;Peripheral;Phenotype;Physicians;Physiological;Physiological Processes;Population;Positioning Attribute;postnatal;Process;Proliferating;Rattus;recruit;Regulation;Research;response;Role;Schizophrenia;Scientist;Shapes;Signal Transduction;single-cell RNA sequencing;Site;Skin;Source;Specificity;stem;Stimulus;Supporting Cell;synaptogenesis;Techniques;Testing;Thalamic structure;Time;Tissues;trafficking;Training;transcriptome;transcriptomics;Vascular Endothelial Growth Factors

PROJECT_TITLE: The impact of proliferating mast cells in the developing brain


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

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: NARRATIVE Retinal vascular health, which is important for normal vision, is impaired in children who are born prematurely, patients who suffer from diabetic retinopathy and senior citizens who frequently develop age-related macular degeneration. This proposal focuses on a circulating lipid molecule, called sphingosine 1-phosphate (S1P) which acts on retinal vessels to promote blood vessel health and normal vision. The major aim of the proposal is to understand how S1P function is defective in retinal diseases such as retinopathy of prematurity and S1P inhibitor-induced macular edema, which is anticipated to ultimately lead to new treatments.

PI_NAMEs: HLA, TIMOTHY TUN (contact)

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: Acceleration;Address;Adverse effects;Age related macular degeneration;Anti-Inflammatory Agents;Attenuated;beta catenin;Blindness;Blood;Blood Vessels;Blood-Retinal Barrier;Brain;Bulla;Cell Culture Techniques;cell injury;Cell Survival;Cells;Cellular biology;Child;Childhood;Chromatin;Code;Coupled;Development;Diabetes Mellitus;Diabetic Retinopathy;Disease;Dose Limiting;Drug Targeting;Elderly;Endothelial Cells;Endothelium;Engineering;Environment;Event;Excision;Exhibits;experimental study;Exudative age-related macular degeneration;Eye;FDA approved;Functional disorder;G-Protein-Coupled Receptors;Gene Deletion;Gene Expression;Genes;Genetic;Genetic Transcription;Growth;GTP-Binding Proteins;Health;Hypertension;Hypoxia;Impairment;Inflammation;Inflammatory Response;inhibitor;Injury;insight;Iron;Laboratories;Lead;Ligands;lipid mediator;Lipids;loss of function;macular edema;Maintenance;Mediating;Metabolic;Metabolic stress;Modeling;Molecular;Molecular Chaperones;mouse model;multiple sclerosis treatment;neonatal mice;neuron loss;novel;Nutrient;Omega-3 Fatty Acids;Organ;Pathologic;Pathology;Pathway interactions;Patients;Pericytes;permissiveness;pharmacologic;Phase;Phenotype;premature;Procedures;Process;programs;protein expression;Regulation;Research;Retina;retina blood vessel structure;Retinal Diseases;Retinopathy of Prematurity;Role;Series;side effect;Signal Pathway;Signal Transduction;sphingosine 1-phosphate;Sphingosine-1-Phosphate Receptor;Spinal Cord;Testing;Testis;TFRC gene;Therapeutic;transcription factor;Transcription Factor AP-1;Transcriptional Activation;Transcriptional Regulation;transcriptome;transcriptome sequencing;transcytosis;vascular bed;Vascular Diseases;Vascular Endothelial Cell;Vascular Endothelial Growth Factors;Vascular Proliferation;vesicle transport;Vision;Visual impairment;Work

PROJECT_TITLE: G protein-coupled receptor regulation of transcriptional mechanisms in the retinal vasculature.

STUDY_SECTION: VCMB

STUDY_SECTION_NAME: Vascular Cell and Molecular Biology Study Section[VCMB]


NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Cardiovascular;Heart Disease;Kidney Disease;Machine Learning and Artificial Intelligence;Patient Safety;Prevention

ORG_CITY: CHAPEL HILL

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE Hemodialysis patients experience a disproportionately high burden of sudden cardiac death. Medication- provoked sudden cardiac death (i.e. death triggered by QT-prolonging medications) may be preventable and has not been studied enough in this population. Our project aims to uncover medication-related risk factors for sudden cardiac death and develop clinical decision support tools that will promote safer medication prescribing.

PI_NAMEs: FLYTHE, JENNIFER E (contact)

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Anti-Arrhythmia Agents;anti-depressive agents;Anti-emetics;Antibiotics;Arrhythmia;Benefits and Risks;Biometry;Calcium;Cardiac;Cardiovascular system;case control;Cessation of life;Clinical;clinical decision support;clinically relevant;comorbidity;Data;Data Analytics;Dialysis patients;Dialysis procedure;Drug Interactions;Drug Prescriptions;Electrocardiogram;Electrolytes;Electronic Health Record;Emergency Care;End stage renal failure;Epidemiology;Event;experience;Future;General Population;healthy volunteer;Hemodialysis;high risk;Implantable Defibrillators;implementation tool;Individual;Investments;Knowledge;Laboratories;Life;Link;Location;Machine Learning;machine learning algorithm;Maintenance;Medicare;medication safety;modifiable risk;mortality;mortality risk;Observational Study;Online Systems;Outcome;Patients;personalized decision;Persons;Pharmaceutical Preparations;Pharmacology;point of care;Polypharmacy;Population;Potassium;pragmatic trial;Predisposition;Prevention strategy;Publishing;Rest;Risk;Risk Assessment;Risk Factors;Risk-Benefit Assessment;Safety;Selective Serotonin Reuptake Inhibitor;structural heart disease;sudden cardiac death;support tools;Testing;Ventricular;Work

PROJECT_TITLE: QT prolonging medications and sudden cardiac death among individuals on hemodialysis


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: SAN FRANCISCO

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE N-acetyl cysteine (NAC) slows cone photoreceptor death in many animal models of retinal degeneration with different genetic origins and was recently shown to improve cone function in patients with retinitis pigmentosa (RP). This AOSLO Resource Center for the NAC Attack trial will evaluate macular cone photoreceptors in 40 participants assigned to NAC or placebo, providing a sensitive measure of disease progression and response to NAC. Success of this trial may lead to the commercialization of a safe and effective treatment that could prevent blindness in patients with RP.

PI_NAMEs: CARROLL, JOSEPH ;DUNCAN, JACQUE LYNNE (contact)

PROGRAM_OFFICER_NAME: SHOAIBI, AZADEH

PROJECT_TERMS: Abbreviations;Acetylcysteine;adaptive optics;Affect;Agreement;Animal Model;antioxidant therapy;Blindness;Cells;Certification;Cessation of life;Ciliary Neurotrophic Factor;Clinical;clinical imaging;Clinical Management;Clinical Trials;commercialization;Cone;Contralateral;cost;cost effective;Cysteine;Data;density;Development;Disease;Disease Progression;Dose;effective therapy;efficacy testing;Evaluation;Eye;functional improvement;Future;Genes;Genetic;Goals;Healthcare;Human;Human Resources;Image;Imaging Techniques;improved;Individual;Infrastructure;inherited retinal degeneration;Intervention;Investigational Therapies;Light;macula;Measures;Methods;mosaic;Mutation;Night Blindness;non-invasive imaging;Ophthalmoscopy;Optical Coherence Tomography;Oral;Outcome Measure;oxidative damage;Oxidative Stress;Participant;participant enrollment;Patients;Peripheral;Persons;phase III trial;photoreceptor degeneration;Photoreceptors;Placebo Control;Placebos;prevent;Randomized;Reading;Resolution;Resources;response;Retina;Retinal Cone;Retinal Degeneration;Retinitis Pigmentosa;Rod;Role;Safety;Scanning;Site;Structure;success;System;targeted treatment;Testing;therapy development;Time;Training;treatment duration;treatment effect;treatment trial;United States;Validation;Vertebrate Photoreceptors;Vision;Visit;Visual Acuity;Visual Fields

PROJECT_TITLE: NAC Attack AOSLO Reading Center


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Sexually Transmitted Infections;Tickborne Diseases;Vector-Borne Diseases

PHR: PROJECT NARRATIVE Herpes simplex virus (HSV) infects epithelial cells, causing cold sores and genital lesions, and spreads to neurons in which it establishes a life-long infection. We will investigate the protective effects of the cytokine interferon lambda acting specifically in the skin to limit HSV lesion severity during acute and recurrent infection. We also will investigate whether interferon lambda limits the spread of mosquito-borne and tick-borne viruses when they are inoculated into the skin by a feeding arthropod.

PI_NAMEs: LAZEAR, HELEN  (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Acute;acute infection;Afferent Neurons;Anatomy;animal imaging;Animals;Anti-viral Response;antiviral immunity;Arboviruses;Arthropods;Bacteria;Biological Models;Blood;Bone Marrow;Bypass;cell type;Chimera organism;conditional knockout;Culicidae;cytokine;Dendritic Cells;Disease;Encephalitis;Epithelial Cells;Epithelium;Event;Exhibits;feeding;Flavivirus;Flavivirus Infections;Focal Infection;fungus;Genetic Transcription;Genitalia;Herpes Labialis;Herpesviridae;Herpesvirus 1;Human;Image;Immune;Immune response;immunoregulation;Infection;Infection Control;Infectious Skin Diseases;Inflammation;Inflammatory;insight;interferon-alpha B;Interferons;Invaded;Investigation;keratinocyte;Keratitis;Kinetics;Knockout Mice;Langat virus;latent infection;Lesion;Leukocytes;luminescence;Maintenance;Mediating;Modeling;mosquito-borne;mouse model;Mus;Neurons;neutrophil;Neutrophil Activation;Neutrophil Infiltration;novel;orofacial;pathogen;Pathogenesis;Pathogenicity;Pathology;Play;Population;Production;programs;protective effect;reactivation from latency;Recurrence;Recurrent disease;recurrent infection;response;Role;Saliva;Severities;Severity of illness;Signal Transduction;Simplexvirus;Site;Skin;skin barrier;skin disorder;skin lesion;Spinal Ganglia;subcutaneous;Surface;tick-borne flavivirus;tick-borne virus;vector;vector tick;Viral;Viral Load result;Viremia;Virus;Virus Replication;Wild Type Mouse;Zika Virus

PROJECT_TITLE: Antiviral and immunomodulatory effects of interferon lambda in the skin

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


NIH_SPENDING_CATS: Chronic Obstructive Pulmonary Disease;Lung;Lymphatic Research;Tobacco;Tobacco Smoke and Health

ORG_CITY: NEW YORK

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: Project Narrative Chronic Obstructive Pulmonary Disease (COPD) affects over 14 million individuals in the United States, but the underlying factors that determine why some individuals develop progressive COPD while others do not have not been fully elucidated. This proposal will determine how injury and clot formation in specialized vessels called the lung lymphatics are early and defining events in the pathogenesis of COPD that contributes to disease progression. We will also test how existing drugs can be used to target the lymphatics for therapy in COPD.

PI_NAMEs: REED, HASINA OUTTZ (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: Address;Affect;Automobile Driving;Biology;Blood;Cause of Death;cell injury;Cells;Chronic Obstructive Pulmonary Disease;cigarette smoke;cigarette smoke-induced;cigarette smoke-induced lung injury;clinical investigation;clinically relevant;Coagulation Process;Data;Disease;Disease Progression;endothelial dysfunction;Event;experience;exposure to cigarette smoke;FDA approved;Genetic;Goals;Hospitalization;Human;Immune;Immunohistochemistry;Immunology;Impairment;in vitro activity;in vivo;Individual;Inflammation;inflammatory lung disease;inflammatory milieu;Inflammatory Response;inhibitor;Injury;Journals;Knowledge;Link;Liquid substance;Lung;lung injury;Lymph;lymph flow;Lymphatic;Lymphatic Diseases;lymphatic drainage;lymphatic dysfunction;Lymphatic Endothelial Cells;Lymphatic Endothelium;Lymphatic function;lymphatic vessel;Maps;Measures;Mediating;Modeling;Molecular;mouse model;Mus;novel;PAR-1 Receptor;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Phenotype;Positioning Attribute;Proteomics;Publishing;Pulmonary Emphysema;pulmonary function;Pulmonary Inflammation;Reporting;response;Role;Severity of illness;Signal Transduction;single-cell RNA sequencing;Structure of parenchyma of lung;symptomatic improvement;targeted agent;Techniques;Testing;Therapeutic;Thrombin;Thrombin Receptor;Thromboplastin;Thrombosis;thrombotic;Time;Tissues;tool;transcriptome sequencing;United States;Up-Regulation;Work

PROJECT_TITLE: Lymphatic Dysfunction in the Pathogenesis of COPD

STUDY_SECTION: RIBT

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


ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: Project Narrative The world-wide epidemic of obesity represents a major public health threat at the nexus of inflammatory disorders, cardiovascular disease, and diabetes mellitus. Our proposed studies are based on our exciting prior finding that eating at the `wrong' time of day, as occurs in shift work and sleep disorders, leads to visceral adiposity and inflammation, while restricting high fat feeding to the `right' time of day promotes healthful obesity. Here we propose to dissect the mechanisms regulating day/night nutrient handling using metabolic flux in tandem with transcriptomic and genomic analyses in adipocytes, and we will combine studies of time-restricted feeding with powerful transgenic models to elucidate how high-fat feeding and related circadian disruption contribute to the immunometabolic complications of obesity at the level of the adipocyte.

PI_NAMEs: BASS, JOSEPH  (contact)

PROGRAM_OFFICER_NAME: SILVA, CORINNE M

PROJECT_TERMS: Adipocytes;Adipose tissue;Animals;ARNTL gene;Binge Eating;Biological Assay;blood glucose regulation;Cardiovascular Diseases;cell type;Cells;Chromatin;circadian;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;Citric Acid Cycle;cohort;combat;comparison group;Coupled;Darkness;Data;Deposition;Diabetes Mellitus;Disease;Eating;energy balance;Enzymes;Epigenetic Process;Expression Profiling;Fasting;Fatty acid glycerol esters;feeding;Feeding behaviors;Fibrosis;Functional disorder;Gene Expression Profiling;Genes;Genetic;Genetic Transcription;Genomics;Glucose;Health;High Fat Diet;Impairment;Individual;Inflammation;Inflammatory;insulin sensitivity;Jet Lag Syndrome;Knockout Mice;Label;Light;lipid biosynthesis;Lipids;Liver;Metabolic;metabolic phenotype;Metabolism;Mitochondria;Molecular;Mus;novel;Nutrient;Obesity;Obesity Epidemic;organic acid;overexpression;Overnutrition;Pathway interactions;Periodicity;preservation;Process;programs;Public Health;Regulation;Respiration;respiratory;Role;shift work;Shift-Work Sleep Disorder;Site;Skeletal Muscle;Sleep;social;Stress;Succinates;System;Testing;Time;Time-restricted feeding;Tracer;transcriptomics;Transgenic Model;Transposase;Tricarboxylic Acids;Visceral

PROJECT_TITLE: Cross-regulation of Immunometabolism and Circadian Pathways in Obesity Pathophysiology

STUDY_SECTION: NNRS

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


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Genetics;Heart Disease;Human Genome;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: PROJECT NARRATIVE The regulatory mechanisms involved in maturation of the heart following birth are poorly understood. This is an important area of investigation given that during the development of heart failure the mature adult heart reverts to a more fetal format restricting its capacity for fuel combustion and cardiac performance. This project will investigate a newly discovered master regulatory network involved in maturation of the heart, delineate the mechanisms involved in its dysregulation during the development of heart failure, and will test new therapeutic approaches aimed at heart disease by exploiting this newly discovered circuitry.

PI_NAMEs: KELLY, DANIEL PATRICK (contact)

PROGRAM_OFFICER_NAME: WONG, RENEE P

PROJECT_TERMS: adeno-associated virus 9 delivery;Adult;Area;Automobile Driving;Biogenesis;Birth;Cardiac;Cardiac Myocytes;cardiogenesis;Cells;Complex;coronary fibrosis;Coupled;CRISPR/Cas technology;Data;Development;epigenomics;estrogen-related receptor;Event;fetal;Fetal Development;Fetal Heart;Fibrosis;functional genomics;Funding;Gene Targeting;Genes;Genetic Transcription;Genomics;Goals;Heart;Heart Diseases;Heart failure;Histones;Human;human induced pluripotent stem cells;Hypertrophy;Immunoprecipitation;in vivo;insight;Investigation;Ion Transport;Knock-out;Mass Spectrum Analysis;Metabolic;Mitochondria;Modeling;Morphogenesis;mouse model;Mus;novel;novel therapeutic intervention;novel therapeutics;Nuclear Receptors;Pathologic;Pathway interactions;Performance;Perinatal;Perinatal mortality demographics;postnatal;pre-clinical;prevent;Process;programs;Proteins;Proteomics;Reagent;Role;Signal Transduction;stressor;Structural Genes;System;Testing;Therapeutic Studies;Tissues;transcription regulatory network;validation studies;virtual;whole genome;Work

PROJECT_TITLE: Probing the Cardiac PGC-1 Regulatory Cascade

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MIM-R(01)]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_NAME: SCHEPENS EYE RESEARCH INSTITUTE

PHR: The tremendous promise of mesenchymal stem cells (MSCs) to regulate inflammation is evident in corneal transplantation, where treatment of graft recipients with MSCs has been shown to decrease immune rejection of the donor tissue. However, the precise mechanisms by which MSCs regulate immune cell responses have not been defined. We propose to determine the cellular and molecular interactions by which MSCs modulate immunity in corneal transplantation, anticipating that improved understanding of these mechanisms will yield therapeutic targets that could be useful not only in tissue grafting but in a wide variety of inflammatory and autoimmune disorders.

PI_NAMEs: CHAUHAN, SUNIL K (contact)

PROGRAM_OFFICER_NAME: MCKIE, GEORGE ANN

PROJECT_TERMS: Activated-Leukocyte Cell Adhesion Molecule;Allografting;Antigen-Presenting Cells;Antigens;Autoimmune Diseases;B-Lymphocytes;Binding;Biological Assay;CD80 gene;Cell Adhesion Molecules;cell injury;Cell Maturation;Cell secretion;Cell Therapy;Cells;Cornea;CTLA4 gene;Data;design;Development;Disease;draining lymph node;efficacy evaluation;Endothelial Cells;enzyme linked immunospot assay;experimental study;FOXP3 gene;Frequencies;Generations;Goals;graft function;Graft Survival;Graft Tolerance;Helper-Inducer T-Lymphocyte;Home;human disease;Immune;Immunity;immunoregulation;improved;In Vitro;Inflammation;Inflammatory;Interferon Type II;Interleukin-11;Investigation;isoimmunity;Keratoplasty;Knockout Mice;Laboratories;Lymphoid Tissue;Mediating;Mesenchymal Stem Cells;Molecular;mouse model;Mus;novel;novel therapeutic intervention;ocular surface;Pathogenicity;receptor;reconstitution;Regulatory T-Lymphocyte;Reporter;Reporting;Research;Research Priority;response;Series;Site;Surface;T cell regulation;T cell response;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;Therapeutic;therapeutic target;Tissue Donors;Tissue Grafts;tissue regeneration;TNFSF5 gene;transplant model;Transplant Recipients;Transplantation;Transplantation Tolerance;Work

PROJECT_TITLE: Ocular Immune Regulation by Mesenchymal Stem Cells


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

ORG_CITY: LITTLE ROCK

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: PROJECT NARRATIVE Gammaherpesviruses (GHVs) are ubiquitous viruses that establish lifelong chronic infections that can lead to cancer, especially lymphoma. We identified a host protein, p53, as being critical for limiting mutations and cellular transformation due to GHV infection. Experiments are proposed to further define mechanisms of genetic mutations and tumorigenesis that are restricted by p53 during GHV infection, which could identify targets for therapies to prevent or treat GHV-associated lymphomas.

PI_NAMEs: FORREST, JAMES CRAIG (contact)

PROGRAM_OFFICER_NAME: READ-CONNOLE, ELIZABETH LEE

PROJECT_TERMS: Adult;African Burkitt's lymphoma;Agonist;Animal Model;Animals;Apoptosis;B Cell Proliferation;B-Cell Development;B-Cell Lymphomas;B-Lymphocytes;c-myc Proto-Oncogenes;C-Myc Translocation;Cancer Etiology;Cell Cycle Progression;Cell Differentiation process;Cell Proliferation;Cell Survival;cell type;Cells;Chromosomal translocation;Chronic;chronic infection;co-infection;Data;Defense Mechanisms;Dependence;Development;Disease;DNA Damage;DNA Repair;DNA Sequence Alteration;DNA Tumor Viruses;Epstein-Barr virus LMP-1 protein;Epstein-Barr Virus-Related Lymphoma;Event;experimental study;Funding;gammaherpesvirus;Genes;Genetic;Genome;Genomic Instability;Goals;Heavy-Chain Immunoglobulins;Homologous Gene;Human;Human Herpesvirus 4;Human Herpesvirus 8;human pathogen;in vivo;in vivo evaluation;Incidence;infected B cell;Infection;innovation;Integration Host Factors;IRF4 gene;knockout gene;latent infection;Lymphocyte;Lymphoma;Lymphomagenesis;Malaria;Malignant Neoplasms;Mediating;Membrane Proteins;metaplastic cell transformation;Molecular;Mus;Mutate;Mutation;novel therapeutic intervention;Oncogenes;Parasites;pathogen;Pathogenesis;Pathway interactions;Plasmodium;Plasmodium berghei;prevent;Process;Proliferating;promoter;Proteins;Publishing;Reaction;Resistance;response;Risk;Rodent;Sarcoma;Structure of germinal center of lymph node;synergism;System;Systems Analysis;targeted treatment;Testing;Thymic Lymphoma;TP53 gene;tumor;tumorigenesis;Viral;Viral Genes;Viral Proteins;Virus;Virus Latency;Work

PROJECT_TITLE: Defining mechanisms of gammaherpesvirus-driven genomic instability in B cells

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: SYRACUSE

ORG_NAME: UPSTATE MEDICAL UNIVERSITY

PHR: Project Narrative The proposed research is relevant to public health because it will open new strategies for understanding and treating retinal pathological conditions. The research will provide evidence for a novel mechanism that rod photoreceptors use to operate in room light levels, that is applicable to understanding retinal degenerations, with implications beyond this particular application (Innovation for Emerging Therapy).

PI_NAMEs: SOLESSIO, EDUARDO C (contact)

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TITLE: Contribution of rod photoresponse inactivation kinetics to visual temporal contrast sensitivity in mesopic light.

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Cancer

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: Project Narrative The University of Texas MD Anderson Cancer Center T32 Research Training in Academic Medical Oncology Program is focused on training exceptionally talented and productive MDs and MD/PhDs for a research-oriented career in academic medical oncology. These trainees are exposed to robust didactic, clinical, and lab-based research training experiences as well as a broad range of structured career development opportunities to position the T32 graduates to be the next generation of academically based leaders focused on novel discoveries and clinical translation of their work to improve the lives and outcomes of patients with cancer.

PI_NAMEs: DAVIES, MICHAEL  (contact);DINARDO, COURTNEY

PROGRAM_OFFICER_NAME: BOULANGER-ESPEUT, CORINNE A

PROJECT_TERMS: Medical Oncology;Research Training

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Institutional Training and Education Study Section (F)[NCI-F]


NIH_SPENDING_CATS: Congenital Structural Anomalies;Eye Disease and Disorders of Vision;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Precision Medicine;Rare Diseases

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: RELEVANCE TO PUBLIC HEALTH To develop effective therapies for rare monogenic diseases, knowledge of both genetic and environmental factors that might influence disease development and potential responses to therapeutics is extremely important. These factors which may alter disease onset, severity, and clinical appearance may thereby, alter response to treatments. Identification of these “modifiers” promises to deepen our understanding of pathogenic mechanisms, yield new potential targets for therapeutic intervention, and enhance the use of precision medicine to improve treatments. In this application, we focus on the pathogenic mechanisms that underlie CRB1-associated retinal diseases.

PI_NAMEs: NISHINA, PATSY M (contact)

PROGRAM_OFFICER_NAME: SHEN, GRACE L

PROJECT_TERMS: Ablation;Address;Adult;Affect;Age of Onset;Alleles;Animal Model;Appearance;arteriole;Atrophic;Biological;blind;Blindness;cell type;Cells;Characteristics;Child;Clinical;Coats' disease;cone-rod dystrophy;CRISPR/Cas technology;Cystoid Macular Edema;Development;Diagnosis;differential expression;Disease;disease phenotype;disease prognosis;early onset;effective therapy;Enhancers;Environmental Exposure;Environmental Risk Factor;Family;gene augmentation therapy;Genes;Genetic;Genome;Genotype;Heritability;Human;improved;insight;Knock-out;Knowledge;Lead;Leber's amaurosis;Leber's disease;macula;Mediating;Mendelian disorder;Microphthalmos;Modification;Molecular;Monoclonal Antibodies;mouse model;Mus;mutant;Mutation;Onset of illness;Optic Disk Drusen;Pathogenicity;Pathologic;Pathology;Pathway Analysis;Pathway interactions;Patients;Pattern;personalized medicine;Phenotype;Pigmentation physiologic function;Pigments;Population;pre-clinical;precision medicine;preservation;prevent;Progressive Disease;Protein Isoforms;Public Health;Reporting;Resources;response;Retina;Retinal Detachment;Retinal Diseases;Retinitis Pigmentosa;Retinoschisis;Role;segregation;Severities;Severity of illness;Specificity;targeted treatment;Telangiectasis;Testing;Therapeutic;therapeutic evaluation;Therapeutic Intervention;therapeutic target;Tissues;Treatment outcome;treatment response;Variant;Venous

PROJECT_TITLE: Genetic Modifiers of Retinal Disease

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: EMORY UNIVERSITY

PHR: PROJECT NARRATIVE Atherosclerosis is an inflammatory disease, occurring preferentially in arterial branch points exposed to pro- atherogenic disturbed blood flow, while the straight parts of arteries exposed to stable flow are spared. Here, we propose a novel hypothesis that disturbed flow increases the expression of CEBPb protein in endothelial cells, which triggers them to become an unhealthy type known as “endothelial reprogramming,” leading to atherosclerosis development. Our study is designed to uncover the mechanisms by which disturbed flow triggers endothelial programming and atherosclerosis and identify potential antiatherogenic therapeutics.

PI_NAMEs: JO, HANJOONG  (contact)

PROGRAM_OFFICER_NAME: PLAYFORD, MARTIN P

PROJECT_TERMS: Acute;Address;Animal Model;Antiatherogenic;Antibodies;Aorta;Arteries;atherogenesis;Atherosclerosis;Binding;Biological Assay;Blood flow;cancer type;carcinogenesis;CCRL2 gene;Cells;Chromatin;Chronic;chronic inflammatory disease;Coronary;Coronary artery;Data;Data Set;design;Development;Diet;Disease;Embryo;Endothelial Cells;endothelial dysfunction;Endothelium;epigenome;epigenomics;Exposure to;expression vector;Fibroblasts;Gene Expression Regulation;Genes;Genetic Markers;Genome;Human;hypercholesterolemia;imaging modality;Immune;in vivo;Inflammation;Inflammatory;inhibitor;interest;Knowledge;Left;Length;Ligation;Literature;Mesenchymal;Messenger RNA;Metabolic;Methods;Modeling;multiple omics;Mus;mutant;Myocardial Infarction;new technology;novel;Nuclear;Open Reading Frames;overexpression;Pathway interactions;Peripheral arterial disease;Phenotype;Plasmids;Production;Protein Isoforms;Proteins;Proteomics;Regulation;Role;single cell ATAC-seq;single-cell RNA sequencing;Small Interfering RNA;Stains;Stroke;Tertiary Protein Structure;Testing;Therapeutic;Time;Transcript;transcription factor;transcriptome;transcriptomics;Translating;Translation Initiation;Translations;ultrasound;western diet

PROJECT_TITLE: Role of CEBPb in flow-dependent endothelial dysfunction and atherosclerosis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: NEWCASTLE UPON TYNE

ORG_COUNTRY: UNITED KINGDOM

ORG_FIPS: UK

ORG_NAME: UNIVERSITY OF NEWCASTLE

ORG_ZIPCODE: NE1 7RU

PHR: Many stroke survivors face the daily struggle of living with disability; movement synergies are a major contributor to their impairment. Understanding the neural circuits underlying synergies is the first stage of developing rational therapeutic interventions. Our long-term aim is to develop ways of treating synergies at the circuit level (such as neurostimulation to induce plasticity, or specific drugs), freeing patients to improve their function unencumbered by these intrusive and unwanted movement.

PI_NAMEs: BAKER, STUART N (contact);KRAKAUER, JOHN WALTER

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Acceleration;Address;Anatomy;Animals;Anterior;Area;arm;Automobile Driving;Basal Ganglia;Brain;Cells;Corticospinal Tracts;Data;Deep Brain Stimulation;Development;dexterity;disability;Disease;Dissociation;Dorsal;Drug usage;Elbow;Electrodes;experimental study;Face;Flexor;Hand;Health;Human;Impairment;Implant;improved;instrument;ischemic lesion;kinematics;Laboratories;Lead;Learning;Left;Lesion;Lifting;Limb structure;loss of function;Macaca;magnocellular;Measurement;Measures;Methods;Modeling;Monkeys;Motor;Motor Cortex;Motor Neurons;Movement;Muscle;Muscle Contraction;Nature;neural;neural circuit;neural stimulation;Neurons;novel;novel therapeutics;Operative Surgical Procedures;Parkinson Disease;Pathologic;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Physical therapy;Physiological;post stroke;prevent;Primates;programs;Recovery;Red nucleus structure;Reflex action;Reticular Formation;Shoulder;spasticity;Speed;Spinal;Spinal Cord;Stroke;stroke recovery;stroke survivor;Syndrome;synergism;System;Task Performances;Tendon structure;Tennis;Therapeutic Intervention;Time;Torque;Training;Upper Extremity;Video Recording;Work

PROJECT_TITLE: Locating the neural substrates for the flexor synergy after stroke

STUDY_SECTION: SMI

STUDY_SECTION_NAME: Sensorimotor Integration Study Section[SMI]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

ORG_DEPT: NUTRITION

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

PHR: Project Narrative/Relevance Polycyclic aromatic hydrocarbons and heterocyclic aromatic amines are two groups of ubiquitous environmental pollutants that possess potential, obesogenic effects and may lead to excess weight gain in humans, although prospective evidence is lacking to support or refute the role of these chemicals in obesity etiology in humans. The proposed investigation aims to fill this important knowledge gap by examining these pollutants, as well as their interactions, in relation to short-term weight loss, medium-term weight regain, and long-term weight change in both weight-loss trial and longitudinal observational study settings. This research will generate novel evidence that not only elucidates and substantiates associations between these pollutants and weight gain, and also helps to inform policy- or recommendation-making processes toward reducing exposures and curbing obesity epidemic in the U.S.

PI_NAMEs: SUN, QI  (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: Adipose tissue;Adult;Animal Experiments;Animals;anthropogenesis;Aromatic Polycyclic Hydrocarbons;Basal metabolic rate;Basic Science;Binding;Bioinformatics;Biological Markers;Biometry;bisphenol A;Body fat;Body Weight;Body Weight Changes;Body Weight decreased;carcinogenicity;Centers for Disease Control and Prevention (U.S.);chemical group;Chemicals;Chronic Disease;Collaborations;Coronary Artery Risk Development in Young Adults Study;Critical Pathways;Cross-Sectional Studies;Data;Data Analyses;design;development policy;Diet;dietary;dietary approach;Endocrine disruption;Ensure;environmental chemical;Environmental Health;Environmental Pollutants;Epidemiology;Estrogen Receptors;estrogenic;Etiology;excessive weight gain;Excretory function;experience;Exposure to;follow-up;Food;Gene Expression Profile;Generations;Genetic;Grant;Health;heterocyclic aromatic amines;Hour;Human;human data;human subject;improved;Individual;Inflammation;Intake;interest;Intervention;Investigation;Knowledge;Leptin;leptin receptor;Light;Longitudinal, observational study;Measurement;Measures;Meat;Mediating;men;non-smoking;novel;novel strategies;Nurses' Health Study;Obesity;Obesity Epidemic;obesity prevention;obesity risk;obesogen;obesogenic;Outcome;Participant;Pathway interactions;Peroxisome Proliferator-Activated Receptors;Physical activity;Policies;pollutant;Poly-fluoroalkyl substances;Population;Prevalence;Process;Property;prospective;Prospective Studies;Proteins;rapid weight gain;Recommendation;Reproducibility;Research;Research Design;Resources;Risk;Risk Factors;Role;Sampling;Smoking;Source;Thyroid Hormones;Time;Toxicology;trend;urinary;Urine;waist circumference;Weight;Weight Gain;weight maintenance;Woman

PROJECT_TITLE: Environmental Obesogens and Weight Change in the POUNDS LOST Trial

STUDY_SECTION: KNOD

STUDY_SECTION_NAME: Kidney, Nutrition, Obesity and Diabetes Study Section[KNOD]


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Pancreatic islet α cell dysfunction is one of the principal mechanisms underlying the hyperglycemia and impaired response to hypoglycemia in diabetes mellitus. The molecular mechanisms underlying the ability of α cells to maintain synthesis of the counterregulatory hormone glucagon are poorly understood. This study will delineate the communication between two key protein degradative mechanisms, namely endoplasmic reticulum (ER)- associated degradation (ERAD) and macroautophagy, in promoting ER protein quality control and α cell function.

PI_NAMEs: REINERT, RACHEL BYERLEY (contact)

PROGRAM_OFFICER_NAME: WANG, XUJING

PROJECT_TERMS: Address;Affect;Alpha Cell;Autophagocytosis;Beta Cell;Biochemical;biological adaptation to stress;Biosensor;Blood Glucose;blood glucose regulation;career;Cell Line;Cell Physiology;Cell Survival;Cells;Cellular biology;Cellular Morphology;cofactor;Communication;Complex;Data;Defect;Developmental Biology;Diabetes Mellitus;diabetes pathogenesis;Disinhibition;Endocrine;Endoplasmic Reticulum;Ensure;Environment;Excision;Failure;Foundations;Functional disorder;Future;Genetic;Glucagon;glucose metabolism;Homeostasis;Hormones;Human;Hyperglycemia;Hypoglycemia;Image;Impairment;In Vitro;in vivo;inhibitor;insight;Insulin;insulin secretion;Insulin-Dependent Diabetes Mellitus;islet;Islet Cell;Islets of Langerhans;K-Series Research Career Programs;Link;live cell imaging;Maintenance;Mediating;Mentors;metabolic phenotype;Michigan;misfolded protein;Modeling;Molecular;Morphology;mouse model;Mus;novel therapeutic intervention;Organelles;Pancreas;Pathway interactions;peptide hormone;pharmacologic;Physicians;Physiology;prevent;Production;proglucagon;protein aggregation;protein folding;Proteins;proteostasis;Qi;Quality Control;response;Role;Scientist;sensor;Signal Transduction;Structure of alpha Cell of islet;System;Technical Expertise;Techniques;Testing;Therapeutic;Time;Training;Transduction Gene;ubiquitin-protein ligase;Universities;Virus

PROJECT_TITLE: Coordinated functions of ER quality control mechanisms in pancreatic islet α cells

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


NIH_SPENDING_CATS: Genetics

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Project Narrative This project seeks to understand and establish predictive rules for how the alternative splicing of human genes is regulated by splicing factor proteins. These studies will aid in understanding the effects of mutations in splicing factors that occur commonly in blood cancers, and in predicting the effects of sequence variants in the human genome that may cause disease by altering the binding sites of splicing factors in exons and introns.

PI_NAMEs: BURGE, CHRISTOPHER B (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Affinity;Alternative Splicing;Amino Acid Sequence;Binding;Binding Proteins;Binding Sites;Biological;cell type;Cells;combinatorial;crosslink;Data;data integration;Disease;Engineering;Event;Exons;Generations;Genes;Genetic Variation;genomic locus;Goals;Hematopoietic Neoplasms;Human;Human Genetics;Human Genome;Hyperactivity;Immunoprecipitation;improved;In Vitro;in vivo;Individual;Introns;knock-down;Knock-out;Liver diseases;Location;Maps;Messenger RNA;Modeling;Mutate;Mutation;Myotonic Dystrophy;Neurodegenerative Disorders;Organizational Objectives;overexpression;Pattern;Phenotype;Positioning Attribute;Process;Production;Protein Isoforms;Proteins;recruit;Regulation;Repression;RNA;RNA Interference;RNA Primary Transcript;RNA Processing;RNA Splicing;RNA-Binding Proteins;Site;software development;Testing;Tissues;tool;trait;Transcript;transcriptome sequencing;Uncertainty;Variant;Work

PROJECT_TITLE: Function of Sequence-specific RNA Binding Proteins

STUDY_SECTION: GCAT

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Mitochondrial metabolic dysfunction has long been recognized as a key contributor to Alzheimer’s disease (AD); however, the underlying molecular mechanisms of how neurons coordinate mitochondrial activity and how they go awry in AD remain poorly understood. Combining molecular assays in mouse and human neuronal cultures and metabolic imaging in live animal brains, we seek to understand a novel mechanistic link between impaired mitochondrial metabolism, abnormal accumulation of soluble amyloid-β oligomers, Tau dysfunction and insulin resistance in AD. This effort may lead to improved understanding of AD pathogenesis and new therapeutics.

PI_NAMEs: NORAMBUENA, ANDRES M (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: abeta accumulation;abeta oligomer;Affect;age related neurodegeneration;age-related disease;Aging;Alzheimer's Disease;Alzheimer's disease brain;Amino Acids;Amyloid beta-Protein Precursor;Animals;Autophagocytosis;Biological Assay;Biological Markers;Biological Process;Brain;brain cell;Caloric Restriction;Cell Cycle;Cell membrane;Cell model;Cell Physiology;Cell Respiration;Cellular biology;cofactor;Collection;Communication;Complex;detection of nutrient;Deterioration;Development;Disease;Disease Progression;Early Diagnosis;Early treatment;Energy Metabolism;Environment;Experimental Designs;familial Alzheimer disease;fatty acid transport;Fluorescence;fluorescence lifetime imaging;FRAP1 gene;Functional disorder;Hormones;Human;Human Development;human disease;Impaired cognition;Impairment;improved;In Vitro;in vivo;Insulin;Insulin Resistance;Intake;interest;Interruption;Iowa;kinase inhibitor;Libraries;Link;London;Lysosomes;Malignant Neoplasms;Mediating;Metabolic Diseases;Metabolic dysfunction;metabolic imaging;Metabolism;Microscopy;Mitochondria;mitochondrial dysfunction;mitochondrial metabolism;Modeling;Molecular;mouse model;mRNA Translation;Mus;Mutation;Neurodegenerative Disorders;neuron loss;Neurons;Nicotinamide adenine dinucleotide;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutic intervention;novel therapeutics;Nutrient;Organelles;Oxygen;Palliative Care;Pathogenesis;Pathologic;Pathway interactions;Persons;Phosphotransferases;Play;Probability;Production;Protein Biosynthesis;protein complex;Protein Kinase;Provider;Regulation;Research;Role;scaffold;screening;Signal Pathway;Signal Transduction;successful intervention;Swedish mutation;tau aggregation;tau dysfunction;tau interaction;tau Proteins;Testing;Tg2576;Time;Tissues;Toxic effect;two-photon;United States;Work

PROJECT_TITLE: Nutrient-Induced Mitochondrial Activity (NiMA): A Novel Lysosome to Mitochondria Signaling Pathway, its mechanisms and role in Alzheimer's Disease

STUDY_SECTION: NOMD

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


NIH_SPENDING_CATS: Childhood Obesity;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Genetics;Human Genome;Infectious Diseases;Lung;Nutrition;Obesity;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention

ORG_CITY: BALTIMORE

ORG_DEPT: PEDIATRICS

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE The goal of the proposed research is to investigate molecular mechanisms by which maternal obesity, which affects over 50% of U.S. pregnant women, is linked to an increased susceptibility to early life lower respiratory tract infections, the most common cause of hospitalization in U.S. infants. This new knowledge will be highly relevant to understand, prevent, and manage LRTI in early life and help reduce the disproportionally high respiratory morbidity and mortality in this vulnerable age group.

PI_NAMEs: GUTIERREZ, MARIA JIMENA (contact)

PROGRAM_OFFICER_NAME: RUSSO, DENISE

PROJECT_TERMS: Acute;Address;Affect;age group;Antibody Formation;Asthma;Automobile Driving;bead chip;Biogenesis;Biometry;Birth;Boston;Breast Feeding;Cells;Child;Childhood;Chronic;Clinical;cohort;Computational Biology;Computer Analysis;Data;Data Set;defined contribution;design;Development;developmental immunology;dietary;Disease;DNA;DNA Methylation;Early Intervention;Educational workshop;Environment;Epigenetic Process;epigenome;experience;fetal;Foundations;Funding;Generations;Genes;Genomic Segment;Gestational Age;Goals;Health;high throughput analysis;Hospitalization;Human;Hypersensitivity;Immune;immune function;Immune system;Immunity;Immunologist;Immunology;in utero;infancy;Infant;infection risk;innovation;Interdisciplinary Study;International;Knowledge;Lead;Leadership;Learning;Life;Link;Liquid Chromatography;longitudinal analysis;Longitudinal cohort study;Low income;Lower Respiratory Tract Infection;Lymphocyte;Maternal Age;maternal cigarette smoking;maternal obesity;Mediating;meetings;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Metabolic;Metabolic Pathway;metabolic profile;metabolome;metabolomics;Methods;Methylation;methylation pattern;methylome;Minority;Molecular;Molecular Epidemiology;Morbidity - disease rate;mortality;Mothers;novel;novel strategies;obese mothers;Obesity;obesity in children;Overweight;parity;Physicians;Plasma;Population;potential biomarker;Predisposition;Pregnant Women;prenatal;prevent;Prevention;Primary Prevention;programs;prospective;Race;Regulation;Research;Resources;respiratory morbidity;rheumatologist;Risk;Risk Factors;Role;Running;Scientist;Secure;Seminal;sex;Shapes;signature molecule;skills;small molecule;System;Systems Development;tandem mass spectrometry;Testing;therapeutic target;Training;Umbilical Cord Blood;United States National Institutes of Health;Universities;Wheezing;Wood material

PROJECT_TITLE: “Role of Maternal Obesity in Epigenetic and Metabolic Programming and Lower Respiratory Infection Risk in Early Life”

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Health, Behavior, and Context Study Section[CHHD-M]


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

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Tumor-associated macrophages (TAM) represent one of the most abundant immune components in the breast cancer tumor microenvironment and exhibit a robust and unique influence on the disease. How to surmount TAM infiltration and function in order to activate a potent anti-tumorigenic and anti-metastatic response represents a gap in knowledge for the BC field. Continued research is needed to elucidate the interplay between tumor cells and the diverse immune cell populations within the primary tumor microenviornment, and how this interaction shapes tumor biology.

PI_NAMEs: YEH, ELIZABETH S (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: 4T1;Affect;Agonist;Antineoplastic Agents;antitumor effect;Attenuated;Back;Breast Cancer cell line;Breast Cancer Model;Categories;cell type;Cells;Chemoresistance;Clinical;Data;Diagnosis;Disease;Down-Regulation;Endowment;Epidermal Growth Factor Receptor;Exhibits;Extracellular Matrix;FDA approved;Flow Cytometry;Genetic Transcription;Goals;Grant;Human;Immune;Immune checkpoint inhibitor;Immunohistochemistry;Immunosuppression;Impairment;improved;in vivo;in vivo Model;Individual;Infiltration;Inflammatory;Interleukin 4 Receptor;Interleukin 6 Receptor;Interleukin-4;Invaded;knock-down;Knowledge;loss of function;Lymphocytic Infiltrate;Macrophage;Macrophage Activation;Malignant Breast Neoplasm;mammary;Mammary Neoplasms;Measures;Mediating;Methods;Modeling;mouse model;Neoplasm Metastasis;neoplastic cell;paracrine;Paracrine Communication;Patients;Phenotype;Phosphorylation;Phosphotransferases;Play;Population;Primary Neoplasm;Production;Prognosis;Receptor Signaling;Recovery;recruit;Regulation;Research;response;Role;Sampling;Shapes;Signal Pathway;Signal Transduction;single-cell RNA sequencing;small hairpin RNA;Stat3 Signaling Pathway;Testing;therapeutic evaluation;Time;transcription factor;triple-negative invasive breast carcinoma;tumor;Tumor Angiogenesis;Tumor Biology;tumor microenvironment;Tumor Promotion;Tumor-associated macrophages;Tumor-Infiltrating Lymphocytes;tumorigenic;Up-Regulation;Work

PROJECT_TITLE: Tumor cell -TAM Paracrine Signaling in Breast Cancer

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Eye Disease and Disorders of Vision;Intellectual and Developmental Disabilities (IDD);Neurosciences

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Narrative In this project we will test the impact of amblyopia, a developmental disorder due to disruption of binocular vision, on cortical visual processing. Our main goal is to clarify the neural deficits that underlie impaired spatial frequency encoding, reduced contrast sensitivity, reduced stereoacuity and impaired global motion processing in amblyopic compared to healthy human adults.

PI_NAMEs: NASR, SHAHIN  (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: 3-Dimensional;Adult;Affect;Amblyopia;Animals;Anisometropia;Area;area striata;area V2;behavior test;Behavioral;behavioral impairment;Binocular Vision;Biological Markers;biomedical imaging;Brain;Cells;Classification;Color;Contrast Sensitivity;Cortical Column;Cues;developmental disease;Diagnosis;Disease;early childhood;effectiveness evaluation;Environment;extrastriate;extrastriate visual cortex;Eye;Eye Development;Frequencies;Functional Magnetic Resonance Imaging;Goals;High Prevalence;Human;Hyperacusis;Impairment;in vivo;Individual;Knowledge;Life;Link;magnocellular;Maps;Measures;Mediating;Methods;Modeling;Modernization;Motion;Motion Perception;neural;neuroimaging;neuromechanism;Ocular dominance columns;parvocellular;Perception;Persons;Physiological;Population;preference;preservation;Property;Reporting;Resolution;response;Stimulus;Strabismus;Stream;Structure;Techniques;Technology;Testing;Thick;Thinness;tool;Vision;Vision Disorders;Visual Cortex;Visual impairment;Visual Perception;visual processing;Visual System

PROJECT_TITLE: Applications of high resolution fMRI in ultra-high field (7T) in revealing developmental disorders underlying amblyopia


NIH_SPENDING_CATS: Aging;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: PHILADELPHIA

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: There is intense interest in the circuits regulated by niches that guide stem cell behavior. It is not understood how the niche is specified and assembled in a tissue, and then how it executes control over the stem cell pool. Understanding these interactions will be crucial to the use of stem cells in regenerative medicine. !

PI_NAMEs: DINARDO, STEPHEN FRANCIS (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Ablation;Actomyosin;Address;Aging;Architecture;Biological;Biological Assay;Biological Process;cancer cell;cell behavior;Cell Physiology;Cells;Centrosome;Communication;Cytoskeleton;Defect;Excision;Funding;Genetic;Genetic Transcription;Homeostasis;Image;interest;Knowledge;Lasers;Maintenance;Mechanics;Morphogenesis;Normal Cell;Property;Regenerative Medicine;Signal Transduction;Specific qualifier value;stem cells;Stress;Tissues;virtual;Work

PROJECT_TITLE: Control of Stem Cell Dynamics by a Niche at Steady-State and During Aging

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


NIH_SPENDING_CATS: Asthma;Behavioral and Social Science;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Networking and Information Technology R&D (NITRD);Pediatric;Prevention;Social Determinants of Health;Telehealth

ORG_CITY: CHICAGO

ORG_NAME: LURIE CHILDREN'S HOSPITAL OF CHICAGO

PHR: PROJECT NARRATIVE The proposed research is relevant to population health because pediatric asthma is a common chronic condition that affects millions of U.S children, especially children from urban, low-income communities. Children with persistent and poorly-controlled asthma should be taking a daily preventive medication, like inhaled corticosteroids, to reduce their risk for breathing problems leading to frequent emergency department visits and hospitalizations; however, a wide gap exists between what is recommended and adherence to medications. This project investigates using user-centered design methods and implementation science research to enhance a digital outpatient asthma intervention to improve asthma symptoms and adherence to medications.

PI_NAMEs: KAN, KRISTIN  (contact)

PROGRAM_OFFICER_NAME: FREEMER, MICHELLE M

PROJECT_TERMS: 11 year old;Absenteeism;acceptability and feasibility;Acute;Address;Adherence;Administrator;Adrenal Cortex Hormones;Advisory Committees;Affect;Asthma;asthmatic patient;Breathing;career development;Caregiver support;Caregivers;Caring;Child;Child Care;Child Support;Childhood;Childhood Asthma;Chronic;Chronic Disease;Clinic;Clinical;clinical care;clinical decision support;Clinical Investigator;Clinical Trials Design;Communication;Communities;Competence;Data;Data Analyses;Dedications;design;Detection;Development Plans;Diabetes Mellitus;digital;Educational workshop;effective intervention;effectiveness/implementation study;effectiveness/implementation trial;electronic sensor;Emergency department visit;Enhancement Technology;Environment;Evaluation;evidence base;experience;Feasibility Studies;feasibility testing;feasibility trial;Feedback;Funding;Future;Goals;Guidelines;health care delivery;health care service;health care settings;Health Personnel;Health system;Health Technology;Healthcare;healthcare burden;high risk;high risk population;Home;Hospitalization;Household;implementation design;implementation science;implementation strategy;improved;improved outcome;informant;Inhalation;Inhalators;Integrated Health Care Systems;Intervention;Interview;Learning;Literature;longitudinal analysis;Low income;medication compliance;Mentored Clinical Scientist Development Program;Mentors;Mentorship;Methods;mHealth;mhealth interventions;mobile application;mobile sensor;Monitor;Outcome;Outpatients;patient oriented;patient-clinician communication;Patients;Pediatric Hospitals;Pharmaceutical Preparations;Physicians;pilot trial;Population;population health;Population Study;Preventive;Process;Quality of Care;Randomized;Randomized, Controlled Trials;Recommendation;reduce symptoms;Reporting;Research;research and development;Research Infrastructure;Research Methodology;Research Personnel;Risk;Schools;Scientist;Self Management;sensor;Series;Services;Signal Transduction;skill acquisition;skills;socioeconomics;statistical learning;Symptoms;Techniques;Technology;Testing;tool;Training;United States National Institutes of Health;Universities;urban children;user centered design;wireless;World Health

PROJECT_TITLE: Technology-Enhanced Asthma Care in Children at Clinic and Home (TEACCCH) Study

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(OA)]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Building Research Capacity at Institutions with Limited NIH Funding;Substance Misuse

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: The University of Nebraska Summer Undergraduate Alcohol Research Program provides undergraduate students with a 10-week mentored research experience with training in alcohol pathophysiology and scientific skills.

PI_NAMEs: BAILEY, KRISTINA L (contact)

PROGRAM_OFFICER_NAME: LIN, LI

PROJECT_TERMS: alcohol consequences;Alcohol consumption;alcohol exposure;alcohol misuse;alcohol research;alcohol use disorder;Alcohols;Biomedical Research;Body System;career;Cause of Death;Communities;Crime;Data;Dedications;Development;Educational process of instructing;experience;Exposure to;Faculty;Financial Hardship;follow-up;Functional disorder;Funding;Goals;graduate school;hazard;Health;health care service utilization;Health Occupations;Human;Imprisonment;improved;Infrastructure;Interdisciplinary Study;interest;Journals;Laboratories;Leadership;Learning;life span;Medical center;Mentors;Modeling;National Institute on Alcohol Abuse and Alcoholism;Nebraska;next generation;pandemic disease;Persons;Play;Population;Positioning Attribute;Prevention;Productivity;programs;Recording of previous events;recruit;Reporting;Research;Research Personnel;Research Project Grants;resilience;Schools;Science;Scientist;skills;student participation;Students;substance use;success;symposium;Training;trend;undergraduate research experience;undergraduate student;Underrepresented Minority;United States;Universities;virtual;Work

STUDY_SECTION: AA

STUDY_SECTION_NAME: Epidemiology, Prevention and Behavior Research Study Section[AA-2]


NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Cancer;Orphan Drug;Ovarian Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Women's Health Research

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Relevance to public health: Recent pre-clinical and clinical studies have shown that mesenchymal stem cells hold tremendous promise for the treatment of cancer. The goal of this research is to develop a non-surgical, targeted and clinically translatable stem cell-based platform that can be used for the treatment of recurrent and metastatic ovarian cancer.

PI_NAMEs: HATEFI, ARASH  (contact)

PROGRAM_OFFICER_NAME: MCKEE, TAWNYA C

PROJECT_TERMS: ABCB1 gene;ABCG2 gene;adipose derived stem cell;advanced disease;Adverse effects;aldehyde dehydrogenases;anti-cancer;Antineoplastic Agents;Ascites;Biodistribution;bioluminescence imaging;cancer cell;Cancer Patient;Cancer Relapse;cancer therapy;carboxylesterase;Cell Cycle Progression;cell type;Cells;cellular targeting;chemotherapy;Cisplatin;Clinic;Clinical Research;clinical translation;Clone Cells;cytokine;Cytosine deaminase;Data;Death Rate;Diagnosis;Disease;Disease Resistance;DNA biosynthesis;Drug Delivery Systems;Drug Efflux;Drug resistance;Drug Targeting;Effectiveness;efflux pump;Engineering;enzyme activity;Enzymes;Epithelial ovarian cancer;esterase;Evaluation;Excision;experience;extracellular;Flucytosine;Fluorouracil;Genetic Engineering;Genomics;Goals;Greater sac of peritoneum;Hematology;Histocytochemistry;Histopathology;Human;humanized mouse;Hypoxia;Immunocompromised Host;Immunohistochemistry;In complete remission;Inflammatory Response;intraperitoneal;irinotecan;Magnetic Resonance Imaging;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Maps;Measures;Mesenchymal Stem Cells;Metastatic/Recurrent;migration;Modality;Molecular;Mus;Names;nanoluciferase;Necrosis;Neoplasm Metastasis;Normal tissue morphology;Operative Surgical Procedures;Outcome;Ovarian;ovarian neoplasm;Ovary;overexpression;Paclitaxel;Patient Care;Patients;Penetration;Pharmaceutical Preparations;Platinum;Population;preclinical study;prevent;Prodrugs;Prognosis;Property;Public Health;Publishing;Recording of previous events;Recurrence;Recurrent tumor;Regimen;Relapse;relapse prevention;Research;Resistance;resistance mechanism;response;SN-38;standard of care;Statistical Data Interpretation;stem cell migration;stem cells;stem-like cell;success;Supporting Cell;Survival Rate;System;targeted treatment;Technology;Therapeutic;Tissues;Topoisomerase I inhibition;Toxic effect;treatment response;Treatment Side Effects;Tropism;tumor;Tumor Burden;Tumor Debulking;Tumor Tissue;tumor xenograft;United States;Unresectable;Yeasts

PROJECT_TITLE: Stem Cell-based Platform for Targeted Enzyme/Prodrug Therapy of Recurrent Ovarian Cancer

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


ORG_CITY: Columbus

ORG_DEPT: NEUROLOGY

ORG_NAME: OHIO STATE UNIVERSITY

PHR: Project Narrative: Regulatory T cell-antigen presenting cell contact can result in antigen specific suppression of effector T cells. The biological processes leading up to antigen specific immune suppression can serve as potential therapy targets for restoring self-tolerance in autoimmune diseases. This project proposes to delineate these biological processes for the first time in man resulting in the development of antigen-targeted therapies against autoimmune diseases.

PI_NAMEs: AKKAYA, BILLUR  (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: Address;Adult;Affect;Antigen Receptors;Antigen Targeting;Antigen-Presenting Cells;Antigens;Attention;Autoantigens;Autoimmune Diseases;Autoimmunity;autoreactive T cell;autoreactivity;Award;Binding;Biological Process;Biological Response Modifier Therapy;Bystander Suppression;Cell Communication;Cell Count;Cell membrane;Cell Physiology;Cell surface;Cells;Cessation of life;Chronic;Chronic Disease;Clinical Trials;Clonality;Clone Cells;combat;Complex;Conceptions;Defect;Defense Mechanisms;Dendritic Cells;Development;Discrimination;Disease;Disease Progression;Dose;effector T cell;Epitope spreading;Epitopes;Event;Excision;experimental study;Flow Cytometry;Future;Genes;Health;Helper-Inducer T-Lymphocyte;Histocompatibility Antigens Class II;Human;Immune response;Immune system;Immune Targeting;Immune Tolerance;immunomodulatory strategy;Immunosuppression;Immunotherapy;In Vitro;in vivo;Individual;Infection;Inflammation;Insulin-Dependent Diabetes Mellitus;Interleukin-2;Knowledge;Left;Malignant Neoplasms;man;Mediating;Methods;middle age;Mission;Modality;Molecular;mortality;National Institute of Allergy and Infectious Disease;Nature;novel;novel strategies;Organ;Outcome;Outcome Study;Paracrine Communication;Pathologic;Pathway interactions;Patients;Peptides;peripheral tolerance;Population;Precision therapeutics;Prevalence;prevent;Regulatory T-Lymphocyte;Reporting;Role;Self Tolerance;Shapes;Signal Transduction;Specificity;stem;Stimulus;Surface Antigens;T cell therapy;T-Cell Receptor;T-Lymphocyte;T-Lymphocyte Subsets;targeted treatment;Techniques;Testing;therapeutically effective;Thymus Gland;Time;Tissues;treatment strategy;two photon microscopy;United States;Visualization;Western Blotting

PROJECT_TITLE: Deciphering the specificity and molecular mechanisms of regulatory T cells using novel approaches


NIH_SPENDING_CATS: Aging;Neurosciences

PHR: PROJECT NARRATIVE The metabolic sensor mTORC1 has been successfully targeted to promote longevity in a range of species, but the translational capacity of this anti-aging intervention to humans is limited by negative side effects and a lack of knowledge about the mechanisms driving lifespan extension. The goal of this project is to investigate how neuron-specific mTORC1 inhibition in C. elegans extends lifespan without impairing growth or development by assessing changes both in the neurons and in peripheral tissues. This work will advance our understanding of both the metabolic regulation of aging and the functions of the mTORC1 pathway in general, and will influence the way we design interventions to promote healthy aging.

PI_NAMEs: SMITH, HANNAH J (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: Affect;Afferent Neurons;Age of Onset;age related;age-related disease;Aging;aging mechanism;anti aging;Automobile Driving;Auxins;Back;Biological;Caenorhabditis elegans;Categories;cell growth;Cells;cellular development;Chimeric Proteins;Chronic Disease;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Data;design;Development;Disease;experimental study;extend lifespan;Fertility;FRAP1 gene;Genes;Genetic Models;gerotherapeutic;Goals;Growth;Growth and Development function;Health;healthy aging;Human;human old age (65+);Immunoprecipitation;Impairment;Individual;Induced Neurons;Intervention;Intestines;Knowledge;life span;Longevity;Mediating;Mediator;Metabolic;Metabolic Pathway;Mitochondria;Motor Neurons;mutant;Neurons;Neuropeptide Gene;neurotransmission;neurotransmitter release;Nutrient;Pathway interactions;Peripheral;pharmacologic;Phenotype;prevent;Process;Proteins;rate of aging;Regulation;Reproducibility;Reproduction;Resistance;Ribosomes;RiboTag;Risk Factors;RNA;RRAGA gene;sensor;Shapes;side effect;Signal Induction;Signal Pathway;Signal Transduction;Signaling Molecule;Specificity;Stress;System;Testing;therapy design;Tissues;tool;transcriptome sequencing;Vesicle;Work

PROJECT_TITLE: Mechanisms of Aging Regulation by Neuronal mTORC1 in C. elegans

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Brain Disorders;Genetics;Mental Health;Mental Illness;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: ATLANTA

ORG_DEPT: GENETICS

ORG_STATE: GA

PHR: Project Narrative (Public Health Relevance Statement) Assembly of inhibitory and excitatory neurons into early networks represents a critical period in cortical development during which early principles of circuit formation and function are established. This elaborate process, which involves inhibitory neurons migrating long distances to eventually integrate with excitatory neurons, is often associated with various neuropsychiatric disorders; however, the basis of how disease-causing mutations affect discreet steps of this process in humans remains unknown. This proposal aims to investigate, using a stem-cell-based model of human cortical development, how distinct mutations in the gene TCF4, each of which has been implicated in distinct disorders such as schizophrenia, intellectual disability and epilepsy, affect the assembly of early human cortical networks. The long-term goal is to attain a comprehensive understanding of disease biology surrounding atypical cortical networks in patients with discrete TCF4 mutations and eventually identify new drug targets that are potentially shared across various disorders.

PI_NAMEs: BIREY, FIKRI  (contact)

PROGRAM_OFFICER_NAME: PANCHISION, DAVID M

PROJECT_TERMS: 3-Dimensional;Affect;autism spectrum disorder;Biological;Biology;Brain;Brain Diseases;Calcium;Cell Line;cell type;Cells;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR/Cas technology;critical period;Data;design;Development;differential expression;Dimerization;Disease;disease phenotype;disease-causing mutation;Dorsal;dosage;Electrophysiology (science);Epilepsy;epileptic encephalopathies;excitatory neuron;Exhibits;experimental study;fetal;Forebrain Development;Functional disorder;Future;gene network;Genes;Genetic;Genetic Predisposition to Disease;Genetic Transcription;genetic variant;Genome;Glutamates;Goals;Human;human induced pluripotent stem cells;human model;In Vitro;inhibitory neuron;insight;Intellectual functioning disability;Interneuron function;Interneurons;Intervention;laboratory experience;Lead;Mediating;Medical Genetics;Mental disorders;Methods;microphysiology system;migration;Migration Assay;Modeling;Modification;Molecular;multiphoton imaging;Mutation;myocyte-specific enhancer-binding-factor 2C;Neurobiology;Neurons;neuropsychiatric disorder;new therapeutic target;novel strategies;optogenetics;Outcome;Pathogenicity;Pathologic;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Phase;Phenotype;Pregnancy;Process;programs;Property;Prosencephalon;public health relevance;Radial;Research;Research Personnel;response;Role;Schizophrenia;skills;Slice;Specific qualifier value;stem cell model;Surveys;Synapses;TCF7L2 gene;Techniques;Testing;Tissues;Training;transcription factor;transcriptome sequencing;transcriptomics;Universities;Variant

PROJECT_TITLE: Investigating the role of TCF4 in human interneuron function and dysfunction

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS