NIH_SPENDING_CATS: Cancer;Genetics;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: The goal of the proposed project is to investigate NUDT5 as a potential target for ovarian cancer treatment. We identified NUDT5 as predicated mechanical regulator of ovarian cancer behaviors associated with elevated levels in increasing ovarian tumor grade. If we can understand how NUDT5 drives ovarian cancer progression, this would guide future therapeutic interventions to improve patient survival.

PI_NAMEs: FLORES, ANGELINA MARYBELLE (contact)

PROGRAM_OFFICER_NAME: ADAMS, GREGORY

PROJECT_TERMS: Actins;Affect;Antineoplastic Agents;Behavior;Biological Assay;Breast Cancer cell line;cancer cell;Cancer Cell Growth;Cancer Patient;cancer subtypes;cancer therapy;cancer type;Carcinoma;cell behavior;Cell Fractionation;Cell Line;cell motility;Cell Nucleus;Cell Physiology;Cell Proliferation;Cell Shape;Cell Survival;Cells;Cellular Morphology;Chemoresistance;chemotherapy;chromatin remodeling;Clear Cell;Clinical Treatment;Complementary DNA;Complementary therapies;Confined Spaces;Cytoskeletal Modeling;Cytoskeleton;Data;differential expression;Disease;DNA Damage;DNA Double Strand Break;DNA Repair;Double Strand Break Repair;Drug Compounding;Drug Targeting;Dyes;F-Actin;Future;G Actin;Generations;Genes;Goals;Histologic;Homeostasis;Human;Hydrolase;imaging system;Immunofluorescence Immunologic;Immunohistochemistry;improved;In Vitro;innovation;insight;Invaded;Knock-out;Knowledge;Libraries;Link;live cell imaging;Malignant neoplasm of ovary;Malignant Neoplasms;Maps;Measures;mechanical behavior;mechanical properties;Mechanics;Mediating;Mediator;member;Meta-Analysis;Metabolism;microdevice;migration;Molecular;Morphology;Motility;Neoplasm Metastasis;Normal tissue morphology;novel;Nuclear;nucleoside diphosphate;Ovarian;ovarian neoplasm;overexpression;Patients;Pharmaceutical Preparations;pharmacologic;Platinum;Poly(ADP-ribose) Polymerase Inhibitor;Production;Proliferating;Recurrence;Resistance;response;Role;Sampling;screening;sensor;Serous;Shapes;Signal Pathway;small hairpin RNA;Speed;spheroids;Structure;Survival Rate;Testing;Therapeutic Intervention;therapeutically effective;Tissue Microarray;transcriptome sequencing;treatment strategy;tumor;tumor progression;Visualization;Western Blotting

PROJECT_TITLE: Defining the role of NUDT5 in ovarian cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09B-Z (20)]


ADMINISTERING_IC: AA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Neurosciences;Substance Misuse

ORG_CITY: CHICAGO

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PHARMACOLOGY

ORG_FIPS: US

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative G protein-coupled receptors (GPCRs) are the primary targets for many prescription drugs and are involved in the regulation of physiological processes needed for survival. This project will determine the GPCR-triggered cyclic adenosine monophosphate (cAMP) and Protein Kinase A (PKA) signaling dynamics in specific cells during the induction of synaptic transmission using an advanced optical imaging technique, fluorescent sensors, and pharmacology. These studies will define the molecular mechanisms underlying neuronal signaling involving GPCR-mediated cAMP-PKA signaling to inform novel drug development strategies.

PI_NAMEs: AUGUSTIN, SHANA M (contact)

PROGRAM_OFFICER_NAME: CUI, CHANGHAI

PROJECT_TERMS: Acute;Adult;Affect;Behavior;Behavioral;Brain;Brain region;brain tissue;career development;Cell Physiology;cell type;Cells;Chemosensitization;Child;Communication;Corpus striatum structure;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Data Analyses;Dendrites;Disease;Doctor of Philosophy;Dopamine;drug development;Drug Prescriptions;Drug usage;Electrophysiology (science);Etiology;experimental study;G-Protein-Coupled Receptors;Glutamates;Goals;graduate school;Image;Imaging Techniques;information organization;laboratory experience;learned behavior;Learning;Ligands;Light;Link;Long-Term Depression;Measurement;Mediating;Memory;Mental Depression;Mentors;Mentorship;Modification;Molecular;Monitor;neural circuit;Neuromodulator;neuronal cell body;Neurons;neuroregulation;Neurosciences;neurotransmission;novel therapeutics;Operative Surgical Procedures;optical imaging;optogenetics;Output;parent project;Pattern;Pharmaceutical Preparations;pharmacologic;Pharmacology;Physiological Processes;Postbaccalaureate;postsynaptic;Preparation;presynaptic;Property;receptor;recruit;Regulation;Reporting;response;Second Messenger Systems;sensor;Signal Pathway;Signal Transduction;Slice;spatiotemporal;Specificity;Students;Synapses;synaptic depression;Synaptic plasticity;Synaptic Transmission;Techniques;tool;Training;transmission process;two photon microscopy;Viral;Writing

PROJECT_TITLE: Diverstiy Supplement-Deep brain live imaging of cAMP and protein kinase A activities underlying synaptic- and circuit-level mechanisms during learned behaviors

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Liver Disease;Substance Misuse

ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: PROJECT NARRATIVE Alcohol consumption is a leading cause of preventable morbidity and mortality worldwide; interactions between cells of the innate immune system and hepatic stellate cells are critical to the development and resolution of fibrosis in patients with ALD. IRF3 is a transcription factor important for anti-viral responses; however, we discovered that, in addition to its transcriptional functions, non-transcriptional function of IRF3 contribute to injury in murine models of ALD. Here we will identify cell specific functions of IRF3 in murine models of fibrosis and identify proximal signaling elements leading to activation of IRF3 in ALD.

PI_NAMEs: NAGY, LAURA E. (contact)

PROGRAM_OFFICER_NAME: WANG, JOE

PROJECT_TERMS: 3-Dimensional;Acceleration;Acute;Alcohol abuse;Alcohol consumption;alcohol exposure;Alcoholic Hepatitis;Alcoholic Liver Diseases;Alcohols;Anti-viral Response;Apoptosis;Apoptotic;Bax protein;Binding;Biological Models;Bone Marrow;Cell Communication;Cell Culture Techniques;Cells;Characteristics;Chronic;Cirrhosis;Clinical;Complex;Data;Death Rate;Development;Disease Progression;Double-Stranded RNA;Elements;Ethanol;Exhibits;experimental study;Exposure to;Extracellular Matrix;fibrogenesis;Fibrosis;Genetic Transcription;Grant;Hepatic;Hepatic Stellate Cell;Hepatitis;Hepatocyte;human induced pluripotent stem cells;Immune;immune cell infiltrate;Immune response;improved;Inflammation;Inflammatory;Injury;innate immune pathways;Innate Immune System;Interferon-beta;Interferons;Investigation;IRF3 gene;Knock-in Mouse;Kupffer Cells;Liver;Liver diseases;Liver Fibrosis;liver inflammation;liver injury;Mediating;Metabolic;Modeling;Molecular Chaperones;monocyte;Morbidity - disease rate;mortality;mouse model;Mus;neutrophil;Neutrophil Infiltration;nonalcoholic steatohepatitis;novel;novel therapeutics;Nuclear Import;p65;Pathogenesis;Pathology;Pathway interactions;Patients;Phenotype;Phosphorylation;Play;Predisposition;prevent;Prevention;pro-apoptotic protein;Production;Prognosis;Proteins;Publishing;recruit;Regulation;Resolution;response;RNA;RNA Polymerase III;Role;Signal Transduction;Sterility;Testing;therapeutic target;therapeutically effective;Transcript;transcription factor;treatment strategy;tumor-immune system interactions;Ubiquitination;Viral;Viral Genes;Viral Physiology;Virus Diseases

PROJECT_TITLE: Transcriptional and non-transcriptional function of IRF3 in ALD

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 KUDS-F (02)]


ADMINISTERING_IC: DK

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE Podocytes are kidney cells that maintain their highly organized structure to serve a crucial role in filtration of toxins and waste from blood. We propose to use cell biology and mechanical engineering techniques to study the role of LIM-nebulette, an actin cytoskeletal protein, in podocytes under stressed conditions. This work can identify therapeutic targets by advancing our understanding of mechanobiological processes related to podocyte resilience under injury or disease conditions.

PI_NAMEs: WRIGHT, JACOB MATTHEW (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Actin-Binding Protein;Actins;Acute;Adriamycin PFS;Adult;Affect;Architecture;Binding;Biomechanics;Biophysics;Blood;blood filtration;Blood Pressure;Bowman's space;Calcium;Calcium Signaling;Cardiac;Cardiac Myocytes;Cardiomyopathies;career;Cell Line;Cells;Cellular biology;Childhood;Chronic Kidney Failure;Clinical;Clover;Coupled;CRISPR interference;Custom;Cytoskeletal Proteins;Cytoskeleton;Data;Data Analyses;density;Disease;End stage renal failure;Endothelium;Engineering;Environment;Enzymes;Epithelial Cells;experience;F-Actin;Fellowship;Fiber;Filtration;Focal Adhesions;Foot Process;Foundations;Genes;glomerular basement membrane;Glomerular Capillary;glomerulosclerosis;Goals;Heart;Hemodialysis;Human;Hypertension;Image;Image Analysis;Immunoprecipitation;improved;In Vitro;in vitro Model;in vivo;induced pluripotent stem cell;Injury;insight;instrument;Intermediate Filaments;Investigation;Kidney;kidney cell;Kidney Diseases;kidney preservation;knock-down;Knock-out;Knockout Mice;Knowledge;Label;Laboratories;Lead;Length;Lentivirus Vector;Maps;Mass Spectrum Analysis;mechanical stimulus;Mechanical Stress;Mechanics;mechanotransduction;Mediating;Microscopy;Modification;Molecular;Molecular Biology;mouse model;Mus;Nature;nebulette;Nonmuscle Myosin Type IIA;novel;Nuclear;operation;organizational structure;Outcome;Patients;Periodicity;phosphoproteomics;Play;podocyte;Predisposition;preservation;pressure;Process;Property;protein expression;Protein Isoforms;Proteins;Proteomics;Pythons;Regimen;Renal function;Renal glomerular disease;Research Personnel;resilience;Role;Running;Sampling;Signal Pathway;Signal Transduction;skills;small hairpin RNA;Solid;spatiotemporal;stable cell line;Stains;Stress;Stress Fibers;Stretching;Structure;Surface;System;Techniques;Technology;Testing;therapeutic target;tool;Toxin;transcriptomics;Urine;wasting;Width;Work

PROJECT_TITLE: The Role of LIM-nebulette in podocyte mechanoresponse

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Fellowships in Kidney, Urology, and Hematology[DDK-G]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Embryonic - Non-Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: INDIANAPOLIS

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Profound hearing loss is a major health problem affecting over 36 million adults and children in America. Stem cells could potentially be used to replace damaged auditory receptor cells in patients with profound hearing loss or to study how to promote regeneration of auditory receptor cells after their degeneration. This study will test how human stem cells can be guided to become functional auditory receptor cells using a novel strategy.

PI_NAMEs: HASHINO, ERI  (contact)

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Adult;Affect;analytical tool;Auditory Receptor Cell;Bioinformatics;Biological;biological systems;Cell Differentiation process;Cell Line;Cell Lineage;Cell Maturation;Cell Separation;Cells;Child;Cleavage Under Targets and Release Using Nuclease;Cochlea;congenital deafness;Data;deaf;Development;differential expression;disease model;DNA Binding Domain;DNA-Binding Proteins;Embryonic Development;engineered stem cells;Engineering;Exhibits;Experimental Models;experimental study;Funding;GATA3 gene;Gene Combinations;Genes;Genetic Transcription;hair cell regeneration;Hair Cells;Health;hearing impairment;hormonal signals;Human;Human Biology;human pluripotent stem cell;human stem cells;inducible gene expression;inner ear development;insight;Investigation;Labyrinth;longitudinal analysis;Mammalian Cell;Modeling;multiple omics;Mus;Mutation;Natural regeneration;novel;novel strategies;Nuclear Orphan Receptor;Nucleic Acid Regulatory Sequences;Organ;Organoids;Patients;Pluripotent Stem Cells;progenitor;Property;Regenerative Medicine;Reporting;RNA;Role;Sensorineural Hearing Loss;Series;single-cell RNA sequencing;Specific qualifier value;stem cells;Supporting Cell;synthetic biology;System;Testing;Therapeutic;Thyroid Hormones;Tissues;transcription factor;transcriptomics;Vestibular Hair Cells;vestibular system

PROJECT_TITLE: Modeling Inner Ear Differentiation with Pluripotent Stem Cells

STUDY_SECTION: BNVT

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


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: Chicago

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: NORTHWESTERN UNIVERSITY

PHR: Project Narrative The proposed competing renewal brings together basic, translational, computational, and clinical investigators to support critical research on the role of the FMR1 gene (a strong candidate gene linked to autism spectrum disorder (ASD)) and pragmatics, the social language skills that are most profoundly affected in ASD. We examine pragmatic language profiles, and potential neural correlates, that extend beyond traditional diagnostic boundaries to show overlap in ASD and individuals who carry mutations in the FMR1 gene, and how such traits are linked to molecular-genetic variation. Study aims will generate findings, resources, and tools that will lead to improved understanding of the etiology and mechanistic underpinnings of pragmatic impairments in ASD.

PI_NAMEs: LOSH, MOLLY C (contact)

PROGRAM_OFFICER_NAME: GILOTTY, LISA

PROJECT_TERMS: Affect;analytical tool;auditory processing;autism spectrum disorder;autism symptoms;Award;Behavioral;biobank;Biological;Candidate Disease Gene;Child;Clinical;clinical heterogeneity;Clinical Investigator;Clinical Trials;Cognitive;Communities;Companions;comparison group;Complex;Data;data harmonization;Data Reporting;data repository;data sharing;design;Diagnosis;Diagnostic;Dimensions;Electrophysiology (science);Etiology;Family;family genetics;First Degree Relative;FMR1 gene;FMR1 Premutation;Fragile X Syndrome;Funding;Future;gaze;Genes;genetic analysis;Genetic study;Genetic Variation;Grain;Impairment;improved;Individual;individuals with autism spectrum disorder;Informatics;innovation;insight;Intervention;Language;language impairment;Life;life span;Linguistics;Link;Machine Learning;Measures;Methods;Modality;Molecular Genetics;multidisciplinary;Mutation;mutation carrier;neural;neural correlate;Neurocognitive;neurophysiology;Neuropsychology;novel;Parents;Pathogenesis;Phase;Phenotype;Population;Research;Research Personnel;Resources;Rest;risk variant;Role;segregation;skills;social;social communication;Speech;speech processing;Subgroup;Symptoms;tool;trait;Translating;translational potential;Variant;Visual;Woman;Work

PROJECT_TITLE: A Family Genetic Study of Autism and Fragile X Syndrome

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging

ORG_CITY: LA JOLLA

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Skeletal muscle is important for function, metabolism, and cardiovascular health, and therefore, muscle injury and disease adversely affect quality of life and healthcare costs. Muscle biopsy is the gold standard for diagnosis and monitoring muscle disease and recovery, but is prone to sampling errors and invasive. Here we propose novel diffusion MRI experiments to accurately and non-invasively assess muscle health and pathology.

PI_NAMEs: BERRY, DAVID BARNES;FRANK, LAWRENCE R;WARD, SAMUEL RICHARD (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: 3-Dimensional;3D Print;Ablation;Address;Affect;Age;Animal Model;Animals;Anisotropy;Area;Atrophic;Biological Markers;Biology;Biopsy;Botox;Brain;cardiovascular health;Cells;Clinical;clinically relevant;Computer Simulation;cost;Data;Diagnosis;diagnosis standard;Diagnostic;Diffusion;diffusion anisotropy;Diffusion Magnetic Resonance Imaging;Direct Lytic Factors;Disease;Disease Progression;Dystrophin;Edema;Engineering;Excision;Exercise;Exhibits;experimental study;Extracellular Matrix;Fascicle;Fatty acid glycerol esters;Fiber;Fibrosis;genetic testing;Goals;Health;Health Care Costs;Histologic;Histology;Human;Hypertrophy;Image;Impairment;in silico;In Vitro;in vivo;Inflammation;injured;Injury;innovation;Isometric Exercise;Joints;Knowledge;Magnetic Resonance Imaging;Measurement;Measures;Membrane;Metabolism;Methods;Microscopic;Modeling;Monitor;Mus;Muscle;Muscle Fibers;Muscle function;Muscular Atrophy;Muscular Dystrophies;Myopathy;nanofabrication;Natural regeneration;Needles;Nerve;Normal Range;novel;Pain;Pathologic;Pathology;Performance;Permeability;Phenotype;Physiologic pulse;Physiology;Production;prognostic;Property;Proteins;Protocols documentation;Quality of life;Rattus;Recovery;response;Sampling Errors;Sarcomeres;Scanning;Sensitivity and Specificity;Series;Signal Transduction;simulation;Skeletal Muscle;Skeletal muscle injury;Sterility;Structure;Structure-Activity Relationship;Techniques;Testing;theories;Time;Tissues;tool;Translating;treatment response;Water;water diffusion

PROJECT_TITLE: Non Invasive Measurements of Muscle Microstructures Assessed by Diffusion Tensor Imaging

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MSOS-G (05)]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Pediatric

ORG_CITY: CHAPEL HILL

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Narrative Craniofacial syndromes are prevalent and represent a major expense to families and the healthcare system. This project examines the role of a novel gene in membrane trafficking and ciliary biology that causes Cardiofacioneurodevelopmental Syndrome when mutated (CFNDS). This project aims to characterize its novel interaction with adaptor protein complexes, providing the first molecular insight into the etiology of CFNDS.

PI_NAMEs: SLOAN, DILLON  (contact)

PROGRAM_OFFICER_NAME: FUQUA, CHANTEL FAYSAN

PROJECT_TERMS: Adaptor Protein Complex 2;Adaptor Signaling Protein;Address;Affect;Anatomy;Basic Science;Bilateral;Binding;Biochemical;Biological Assay;Biology;Brain;Categories;cell assembly;Cell Culture Techniques;Cell membrane;Cell Physiology;Cells;Cilia;cilium biogenesis;Clathrin;cleft lip and palate;Coated vesicle;Coiled-Coil Domain;Color;Complex;Congenital Abnormality;craniofacial;Craniofacial Abnormalities;craniofacial disorder;Cryoelectron Microscopy;Data;Defect;Development;Disease;Eating;Endocytosis;Endosomes;Etiology;Exhibits;experimental study;Family;feeding;Fluorescence Microscopy;functional genomics;Genes;Golgi Apparatus;Health;Healthcare Systems;Immunofluorescence Immunologic;in vivo;Individual;insight;interest;Intracellular Membranes;knock-down;Lipid Bilayers;Maintenance;Mammalian Cell;Mediating;Membrane;Membrane Lipids;Methods;Microcephaly;Molecular;molecular modeling;Morphogenesis;Morphology;Mutagenesis;mutant;Mutate;Mutation;Nature;novel;nutrition;Orbital separation excessive;Pathology;Pathway interactions;Patients;Pattern;Phase;Phosphatidylinositols;preference;Process;protein complex;Proteins;Proteomics;reconstitution;Regulation;Reporting;Research;Resolution;Role;sensor;Signal Transduction;Site;SNAP receptor;Structure;Syndrome;System;Testing;Tissues;Total Internal Reflection Fluorescent;trafficking;Transforming Growth Factor beta Receptors;Western Blotting;Zebrafish

PROJECT_TITLE: Molecular mechanism of CCDC32 in Cardiofacioneurodevelopmental syndrome

STUDY_SECTION: DSR

STUDY_SECTION_NAME: National Institute of Dental and Craniofacial Research Special Grants Review Committee[DSR]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Narrative: mRNA vaccine has great potential for the prophylaxis and treatment of many types of diseases, but current mRNA vaccine has complex and long structures associated with complicated enzymatic synthesis, limited stability, and suboptimal efficacy. Here, we propose to engineer small circular RNAs that are easily and quickly manufactured, efficiently delivered by existing drug delivery systems, highly stable in storage solutions and in live cells, and efficient at eliciting potent and long-lasting immune responses. If successful, this study would lay the foundation to establish small circular RNA as a novel platform of mRNA vaccines. Page 1

PI_NAMEs: ZHU, GUIZHI  (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: adaptive immunity;Address;Adjuvant;Antigen Presentation;Antigen Presentation Pathway;Antigen-Presenting Cells;Antigens;Beds;Benchmarking;Biodistribution;CD8-Positive T-Lymphocytes;Cells;chemical synthesis;Chemicals;Chronic;circular RNA;Cold Chains;Communicable Diseases;Complex;COVID-19;Data;Disease;DNA;Dose;Drug Delivery Systems;Drug Kinetics;Elements;emerging virus;Engineering;Exonuclease;Foundations;Freezing;Genomics;Guidelines;Half-Life;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Immune;Immune response;Immunity;Immunization;immunogenicity;Immunologic Receptors;Immunologic Stimulation;immunoregulation;improved;improved outcome;In Vitro;in vivo;Infection;Innate Immune Response;innovation;Internal Ribosome Entry Site;Kinetics;Life;Liposomes;lymph nodes;Malignant Neoplasms;manufacture;Maps;Mediating;Messenger RNA;Modeling;Modification;mRNA sequencing;Mus;Mutate;Mutation;nanocarrier;nanoparticle;nanoparticle delivery;nanoparticulate;Natural Immunity;neoplasm immunotherapy;novel;Nucleotides;old mice;Outcome;pathogen;Peptides;prevent;Production;prophylactic;Prophylactic treatment;Proteins;Proteomics;Research Personnel;Risk;RNA;RNA Editing;RNA vaccine;Safety;Series;single-cell RNA sequencing;Structure;success;T cell response;T-Lymphocyte;Technology;Temperature;Testing;Tissues;Toxic effect;Transgenic Mice;Translating;Translation Initiation;Translations;Transportation;Treatment Efficacy;tumor;vaccine access;vaccine efficacy;Vaccines;vector;Viral Vector;Virulent;young adult

PROJECT_TITLE: Small Circular mRNA Vaccines

STUDY_SECTION: GDD

STUDY_SECTION_NAME: Gene and Drug Delivery Systems Study Section[GDD]


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Diabetes;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Transplantation

ORG_CITY: SAN FRANCISCO

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Our proposal aims to develop a safe, effective, and retrievable alternative extra-hepatic site for the transplantation of stem-cell-derived beta cells. Building on prior work demonstration that co-transplantation of parathyroid tissue with adult donor islets improves survival and engraftment at an intramuscular injection site in mice, we will introduce factors uniquely expressed by parathyroid gland into stem-cell-derived beta cells using genome engineering strategies. Furthermore, we will also incorporate inducible safety switches that will allow small molecule-driven clearance of residual pluripotent cells following beta cell differentiation, and clearance of the entire graft in the instance of an adverse event.

PI_NAMEs: CHU, SIMON  (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Actins;Address;Adoption;Adult;Adverse event;angiogenesis;Angiogenic Factor;Animals;beta Actin;Beta Cell;beta cell replacement;betacell therapy;Biological Assay;Blood;C-Peptide;Cadaver;candidate identification;Caspase;Cell Death Induction;Cell Differentiation process;Cell Physiology;Cell Survival;Cell Transplantation;Cells;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Custom;Development;Diabetes Mellitus;differentiation in vitro;Disease;DNA cassette;Dose;engineered stem cells;Engraftment;Enzyme-Linked Immunosorbent Assay;Event;Extrahepatic;Frequencies;Genes;genome editing;Genome engineering;Growth;Human;human pluripotent stem cell;Immunoassay;Immunodeficient Mouse;Immunofluorescence Immunologic;Implant;improved;In Vitro;in vitro Assay;in vivo evaluation;Inflammatory;Infusion procedures;Insulin;Insulin-Dependent Diabetes Mellitus;Intramuscular;Intramuscular Injections;Ischemia;islet;Islets of Langerhans Transplantation;Kinetics;Lectin;Liver;Location;Mediating;minimally invasive;Monitor;Mus;neoplastic;non-diabetic;Parathyroid gland;Parathyroid Gland Tissue;parathyroid transplantation;Patients;Perfusion;Physiological;pluripotency;Pluripotent Stem Cells;Portal vein structure;post-transplant;prevent;Reaction;Residual state;Safety;safety engineering;Secondary to;Site;small molecule;Source;stem cell differentiation;stem cell engraftment;Stem cell pluripotency;Stem cell transplant;stem cells;subcutaneous;System;Techniques;Teratoma;Testing;Therapeutic;Time;Tissue Donors;Tissues;Titrations;Transplantation;Treatment Efficacy;treatment strategy;tumorigenesis;Vascularization;vector;Work

PROJECT_TITLE: Enhancing Safety and Efficacy of Stem-Cell Derived Islet Transplantation using CRISPR-Mediated Genome Engineering

STUDY_SECTION_NAME: Fellowships in Diabetes Endocrinology and Metabolic Diseases [DDK-E]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Pancreatic Cancer;Rare Diseases

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Pancreatic adenocarcinoma (PDAC) is a deadly form of pancreatic cancer with a poor prognosis and low survival rate, largely due to its late-stage diagnosis and resistance to chemotherapy and radiation therapy. Epigenetic alterations are known to play a role in the progression of PDAC toward metastasis, but the underlying mediators are largely unknown. This proposal aims to examine the epigenetic landscape of pancreatic cancer and define a novel role for the mitochondrial protein GOT2 (glutamic-oxaloacetic transaminase) in epigenetic reprogramming and in promoting PDAC metastasis.

PI_NAMEs: DIAZ, LUIS FRANCISCO (contact)

PROJECT_TERMS: Address;Adenocarcinoma Cell;Aspartate Transaminase;ATAC-seq;Binding;Bioinformatics;Biological;Cancer Etiology;candidate identification;CDKN2A gene;Cell Line;Cells;Cessation of life;Chemotherapy and/or radiation;ChIP-seq;Clinical;CRISPR/Cas technology;Cytotoxic T-Lymphocytes;Data;Dendritic Cells;design;Development;Diagnosis;differential expression;Disseminated Malignant Neoplasm;Distal;Down-Regulation;Doxycycline;effective therapy;Enhancers;Environment;Environmental Risk Factor;Enzymes;Epigenetic Process;Event;experimental study;Fatty Acids;gain of function;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic risk factor;Genetic Transcription;genome editing;Goals;Health;Histone Deacetylation;Human;Immunohistochemistry;Immunosuppression;implantation;in vivo;Infiltration;Injections;insight;knock-down;KRAS2 gene;Link;loss of function;MADH4 gene;Maintenance;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mediator;Medical;member;Metabolism;Methods;Mitochondria;Mitochondrial Proteins;Modeling;Modification;Molecular;mouse model;Mus;mutant;Mutation;Myeloid Cells;Neoplasm Metastasis;neoplastic cell;novel;Nuclear;Nuclear Hormone Receptors;Oncogenic;Oregon;Outcome;Outcome Study;pancreas development;Pancreatic Adenocarcinoma;Pancreatic Ductal Adenocarcinoma;pancreatic neoplasm;Pathway Analysis;Pathway interactions;Patients;Peroxisome Proliferator-Activated Receptors;Phenotype;Play;PPAR delta;Primary Neoplasm;Prognosis;programs;Radiation therapy;Reporting;Research;Resistance;RNA analysis;Role;Sampling;Science;Site;Site-Directed Mutagenesis;small hairpin RNA;Survival Rate;Tail;Technology;Testing;Tissue Sample;TP53 gene;transcription factor;transcriptome;transcriptome sequencing;tumor;tumor growth;tumor heterogeneity;tumor hypoxia;tumor microenvironment;Tumor Promotion;tumorigenesis;Universities;Variant;Veins;Work

PROJECT_TITLE: Defining the role of the mitochondrial protein, GOT2, in pancreatic cancer metastasis and epigenetic dysregulation


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Contraception/Reproduction;Maternal Health;Pregnancy;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: KANSAS CITY

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE Central to the etiology of disease processes leading to early pregnancy loss, preeclampsia, intrauterine growth restriction, placentae abruption, and pre-term birth is abnormal development of the uterine-placental interface. Morphogenesis of the uterine-placental interface depends on differentiation and actions of the invasive/extravillous trophoblast cell lineage. Elucidation of mechanisms controlling invasive/extravillous trophoblast cell differentiation and its involvement in the development of the uterine-trophoblast cell interface will lead to the discovery of diagnostics for early detection of failures in the establishment of pregnancy and regulatory events that can be targeted for therapeutic intervention.

PI_NAMEs: SPECKHART, SAVANNAH  (contact)

PROGRAM_OFFICER_NAME: RAVINDRANATH, NEELAKANTA

PROJECT_TERMS: Abruptio Placentae;Address;Arteries;Binding;Biological Models;Blood Circulation;Blood flow;Cell Compartmentation;Cell Differentiation process;Cell Lineage;cell type;Cells;Chromatin;cytokine;Dedications;design;Development;Diagnostic;Disease;Early Diagnosis;early pregnancy;early pregnancy loss;Endometrium;Etiology;Event;Failure;Fertility;Fetal Growth Retardation;Fetus;Gases;Gene Expression Regulation;genome-wide analysis;Growth Factor;Human;In Vitro;in vivo;in vivo Model;Incidence;Invaded;LIF gene;LIFR gene;Ligands;Mediating;Mentorship;Modeling;Molecular;Morphogenesis;Mus;Nutrient;Oxygen;Pathogenesis;Pathology;Pathway interactions;Placenta;Postdoctoral Fellow;Pre-Eclampsia;Pregnancy;Pregnancy Complications;Premature Birth;pressure;Process;programs;Rattus;receptor;Regulation;Research;Research Personnel;Research Project Grants;restraint;Role;Signal Transduction;skills;Spiral Artery of the Endometrium;Stat3 protein;stem cell model;targeted treatment;Testing;Therapeutic Intervention;Training;transcription factor;transcriptome;trophoblast;trophoblast stem cell;Uterus;Villous;wasting

PROJECT_TITLE: Invasive trophoblast cell differentiation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F06-J (20)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Asthma;Chronic Obstructive Pulmonary Disease;Climate-Related Exposures and Conditions;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Lung

ORG_DEPT: GENETICS

PHR: PROJECT NARRATIVE Ozone is a common ambient air pollutant that causes pulmonary inflammation and decreased lung function upon acute exposure and is further associated with chronic respiratory diseases including asthma and COPD. There is ample evidence of interindividual variation in response to ozone in humans, but the genetic contribution to this variation is largely unknown. This study will use an in vitro model of the human lung featuring genetic diversity to identify risk variants for severe response to acute ozone exposure, then assess their overlap with asthma and COPD risk variants, which will guide identification of high-risk individuals.

PI_NAMEs: LESTER, SARAH ANN (contact)

PROGRAM_OFFICER_NAME: LU, JINING

PROJECT_TERMS: Acute;Address;Affect;Age;Air;air filter;Air Pollutants;Air Pollution;airway epithelium;airway inflammation;Animal Model;Asthma;asthma exacerbation;Biological Models;bronchial epithelium;Cell Culture Techniques;Cell Separation;Cells;chemokine;Chronic;Chronic Obstructive Pulmonary Disease;chronic respiratory disease;Complex;cytokine;Data;Data Set;demographics;design;differential expression;Disease;Environment;Epithelial Cells;exposed human population;Exposure to;gene environment interaction;Gene Expression;Genes;Genetic;Genetic study;Genetic Transcription;genetic variant;Genetic Variation;genome wide association study;genome-wide;Genotype;Goals;Health Hazards;high risk population;Histologic;Human;human data;improved;In Vitro;in vitro Model;in vivo;Inbred Strains Mice;Individual;Inflammation;Inflammatory Response;inter-individual variation;Interleukin-8;Link;Liquid substance;loss of function;Lung;Lung Diseases;Maps;Mediating;Mendelian randomization;Modeling;Molecular;neutrophil;Neutrophil Infiltration;Ozone;ozone exposure;Pathway interactions;Physiological;Policies;Population;Predisposition;Primary Cell Cultures;Pseudostratified Epithelium;Public Health;pulmonary function;Pulmonary Inflammation;Quantitative Trait Loci;Reaction;Reproducibility;Resources;response;Risk;risk variant;Sampling;Severities;sex;Signal Transduction;Smoking History;Smoking Status;Stimulus;Structure;Structure of parenchyma of lung;Symptoms;Testing;Tissue Banks;Tissues;Training;trait;transcriptome sequencing;transcriptomics;Variant

PROJECT_TITLE: Understanding the Genetic Contributions to Variation in Ozone Exposure Response

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-R (08)]


ADMINISTERING_IC: ES

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Genetics;Human Genome;Prevention

ORG_CITY: Los Angeles

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE: Cells are constantly exposed to DNA damage through internal and external sources which could cause especially detrimental double-strand breaks (DSBs) to form. In the proposed studies, we aim to understand how cells repair DSBs within regions in the chromosome named heterochromatin, which are mostly composed of repeated DNA sequences and are prone to generating genome rearrangements if misrepaired. Using the fruit fly, Drosophila melanogaster, and mammalian cell lines, we will establish how Ulp1, a protein we observed to be vital for timing repair progression, contributes to DSB repair, and how the absence of this protein can lead to genomic instability in the presence of environmental threats, contributing to tumorigenesis.

PI_NAMEs: BUTOVA, NADEJDA  (contact)

PROGRAM_OFFICER_NAME: SHAUGHNESSY, DANIEL

PROJECT_TERMS: Biochemical;Biological Models;carcinogenesis;Cell Line;Cell Survival;Cells;Centromere;Chromosomal Rearrangement;Chromosomes;Complex;Controlled Environment;Dangerousness;Defect;Detection;Development;Disease;DNA;DNA biosynthesis;DNA Damage;DNA Double Strand Break;DNA Maintenance;DNA Sequence;Double Strand Break Repair;Drosophila genus;Drosophila melanogaster;Environmental Exposure;Excision;Exposure to;Genetic;Genetic Recombination;Genome;genome integrity;Genome Stability;Genomic Instability;genotoxicity;Goals;helicase;Heterochromatin;homologous recombination;Human;human disease;Image;Individual;Infertility;insight;Invaded;Ionizing radiation;Knowledge;Left;Lesion;Link;Location;Malignant Neoplasms;Mammalian Cell;Molecular;Mus;Mutation;Names;Normal Cell;Nuclear;Nuclear Pore Complex Proteins;Outcomes Research;Pathway interactions;Peptide Hydrolases;Play;prevent;Prevention;Prevention strategy;Proteins;Proteomics;Publishing;recombinational repair;recruit;Regulation;repaired;Research;response;Role;Site;Source;Structure;Sumoylation Pathway;Testing;Translating;tumorigenesis;Ulp1 protease;Work

PROJECT_TITLE: Understanding the Role of Ulp1 as a clock for heterochromatin repair

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F08-L (20)]


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: Project Narrative The Hippo signaling pathway is fundamental for proper organ development, but little is known about its role in neural crest-derived heart development and how genetic mutations of the pathway contribute to congenital heart defects. The project aims to uncover how Yap/Taz, downstream effectors of Hippo signaling, regulate cardiac neural crest cell migration and differentiation using animal and cell models. This work will lead to an increased understanding of proper heart development and the identification of potential new therapeutic targets for treating and preventing congenital heart defects.

PI_NAMEs: ERHARDT, SHANNON NICOLE (contact)

PROGRAM_OFFICER_NAME: LIDMAN, KARIN FREDRIKSSON

PROJECT_TERMS: Affect;Animal Model;Antibodies;ATAC-seq;Atomic Force Microscopy;biological adaptation to stress;Cardiac;cardiogenesis;Cartilage;Cell Differentiation process;Cell model;cell motility;Cells;Clinical;cohort;comparison control;Complex;conditional knockout;Congenital Abnormality;congenital heart abnormality;Congenital Heart Defects;Cytoskeleton;Data;data modeling;Defect;Development;diagnostic tool;DNA Sequence Alteration;Electron Microscopy;Embryo;Enterobacteria phage P1 Cre recombinase;Etiology;Extracellular Matrix;Focal Adhesions;Gene Expression;Genes;Heart;heart defect;Heart Diseases;Heterozygote;High Prevalence;Homeostasis;Human;human embryonic stem cell;Immunohistochemistry;Impairment;improved;In Vitro;in vivo;insight;interest;Investigation;Knowledge;Link;mechanical force;mechanical signal;Methods;Microfilaments;migration;Molecular;mouse model;multiple omics;multipotent cell;Mus;mutant;Neural Crest;Neural Crest Cell;new therapeutic target;Newborn Infant;novel;novel diagnostics;novel therapeutic intervention;Onset of illness;organ growth;Pathogenicity;Pathway interactions;Patients;Population;prevent;Process;Proliferating;protein expression;Regulation;Reporter;Role;Signal Pathway;Signal Transduction;Small Interfering RNA;stem cell population;Stimulus;System;Therapeutic;Therapeutic Intervention;Tissues;transcriptome sequencing;Transgenic Mice;Work

PROJECT_TITLE: Investigating the role of Yap/Taz in neural crest-derived cardiac development

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-R (20)]


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);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Caregiving Research;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurodegenerative;Neurosciences;Patient Safety;Social Determinants of Health

ORG_DEPT: PSYCHOLOGY

ORG_NAME: RICE UNIVERSITY

PHR: Project Narrative This research is novel in applying the theoretical framework of emotion regulation to understand differences in physiological and cognitive health outcomes in ADRD spousal caregivers. If our hypotheses are supported, this research will broaden our knowledge about the role of emotion regulation in caregiver health and could yield important clinical implications for identifying individuals at risk and designing effective interventions.

PI_NAMEs: BRICE, KELLY N (contact)

PROGRAM_OFFICER_NAME: TORRES, DELANY

PROJECT_TERMS: Adverse effects;Adverse event;adverse outcome;age acceleration;aging related disease;Alzheimer's disease related dementia;Anxiety Disorders;Biological;biological adaptation to stress;biopsychosocial;care giving burden;Caregivers;caregiving;Cell Physiology;Chronic;Chronic Disease;Chronic stress;Clinical;Cognition;Cognitive;cognitive change;cognitive function;cognitive reappraisal;cognitive testing;cytokine;Data;Dementia;dementia risk;design;Diagnosis;effective intervention;emotion regulation;Emotional;Emotions;Exhibits;experience;Family;Future;Health;health difference;health related quality of life;Health Status;Impaired cognition;Impairment;Individual;Individual Differences;Inflammation;Inflammatory;Intervention;Knowledge;Link;Longitudinal Studies;Mediating;Mental Depression;Mental Health;Mitochondria;mitochondrial dysfunction;Modeling;Molecular;novel;older adult;Outcome;Patient Self-Report;perceived stress;Persons;physical conditioning;Physiological;poor health outcome;Population;Prevalence;Process;Production;psychologic;Questionnaires;Reactive Oxygen Species;Research;Research Design;Research Personnel;resilience;response;Risk;Role;showing emotion;Spouse Caregiver;Spouses;Stress;stressor;Testing;therapeutically effective;Vulnerable Populations;Work

PROJECT_TITLE: Biopsychosocial influences on cognitive function in dementia spousal caregivers

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F16-T (20)]


NIH_SPENDING_CATS: Brain Disorders;Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Contraception/Reproduction;Down Syndrome;Estrogen;Genetics;Heart Disease;Intellectual and Developmental Disabilities (IDD);Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Project Narrative Proper establishment of a functional placenta is integral to the short and long-term health of a person. People with Down’s Syndrome develop abnormal placentas and are coincidentally at an increased risk for chronic diseases that are closely associated with placental insufficiency. We hypothesize that the placenta is in part responsible for heart defects in people living with Down’s Syndrome and aim to identify a mechanism by which the placenta can serve as an avenue for therapeutic intervention.

PI_NAMEs: LOGSDON, DEIRDRE  (contact)

PROGRAM_OFFICER_NAME: BARDHAN, SUJATA

PROJECT_TERMS: Abnormal placentation;Address;Adult;adverse pregnancy outcome;Affect;Age;Aneuploidy;atrioventricular septal defect;Binding;BMP4;Body System;Candidate Disease Gene;Cardiac;Cardiac Myocytes;Cause of Death;Cell fusion;Cell Line;Cells;Chromosome 21;Chromosomes;Chronic Disease;comorbidity;Conditioned Culture Media;congenital heart abnormality;Cre lox recombination system;CRISPR/Cas technology;critical congenital heart disease;Cyclic AMP;Defect;Development;Diagnosis;differential expression;Differentiation Antigens;differentiation protocol;Disease;disease phenotype;dosage;Dose;Down's Syndrome;ESR1 gene;Estradiol;Estrogen Antagonists;Estrogen Receptors;Estrogens;Etiology;experimental study;Exposure to;fetal;Fetal Growth Retardation;First Pregnancy Trimester;Forskolin;Foundations;Functional disorder;Future;Genes;Genetic Transcription;Goals;Health;Heart;heart defect;Human;Immunofluorescence Immunologic;Impairment;implantation;improved;in utero;In Vitro;Incidence;Individual;induced pluripotent stem cell;inhibitor;knock-down;lentivirally transduced;Life;Link;malformation;Maternal-Fetal Exchange;Measures;Mediating;Membrane;Modeling;Molecular;Morphology;Mus;NRIP1 gene;overexpression;Pathology;Persons;Phenocopy;Phenotype;Placenta;Placental Insufficiency;placental trophoblasts;Placentation;Pregnancy;Primary Cell Cultures;programs;Receptor Inhibition;Reporting;Repression;Research;Risk;risk mitigation;Role;Second Pregnancy Trimester;sex;Signal Transduction;stillbirth;Syncytiotrophoblast;Techniques;Testing;Therapeutic Intervention;Tissues;Transcript;transcriptome;transcriptome sequencing;Trisomy;trophoblast

PROJECT_TITLE: Defining the link between trisomy 21 and placentation defects


ORG_CITY: STANFORD

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: STANFORD UNIVERSITY

PHR: Pulmonary arterial hypertension (PAH) is a disease associated with endothelial dysfunction and progressive small vessel loss. We have discovered a novel gene called carboxylesterase 1 (CES1) is required for metabolic homeostasis in pulmonary endothelial cells and its loss is associated with metabolic reprogramming and endothelial dysfunction. We speculate that therapeutic interventions that can restore CES1 could serve as novel treatments for PAH.

PI_NAMEs: DE JESUS PEREZ, VINICIO A (contact)

PROGRAM_OFFICER_NAME: XIAO, LEI

PROJECT_TERMS: angiogenesis;Apoptosis;Attenuated;Binding;Binding Sites;Blood Vessels;bone loss;bone morphogenetic protein receptors;Carboxylesterase 1;Cell Physiology;Cell Survival;chromatin immunoprecipitation;Coupling;Development;Disease;DNA;Endoplasmic Reticulum;endoplasmic reticulum stress;Endothelial Cells;endothelial dysfunction;Endothelium;Energy-Generating Resources;Enzymes;Epigenetic Process;epigenetic regulation;fatty acid oxidation;Fluorescent Probes;Functional disorder;functional status;Genes;Genetic;genomic locus;Genus Hippocampus;Glycolysis;hemodynamics;Heterozygote;Histone Deacetylation;Homeostasis;Hypoxia;improved;Inherited;inhibitor;insight;Intravenous;knock-down;Knockout Mice;Life;Link;lipid metabolism;Lipid Peroxides;lipidomics;Lipids;Lung;lung microvascular endothelial cells;lung pressure;lung repair;Measurement;Measures;Metabolic;Methylation;Mitochondria;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;Mutation;nanoparticle;new therapeutic target;Nonesterified Fatty Acids;novel;Oxidative Stress;Pathogenesis;Pathologic;Patients;Penetrance;Phenotype;Predisposition;prevent;promoter;pulmonary arterial hypertension;Pulmonary Hypertension;pulmonary vascular disorder;pulmonary vascular remodeling;pyrosequencing;Rattus;Repression;response;right ventricular failure;Role;Severities;Signal Transduction;Structure of parenchyma of lung;Testing;therapeutic development;Therapeutic Intervention;Time;tool;transcription factor;Vascular remodeling

PROJECT_TITLE: The Role of the CES1 in the Pathogenesis of Pulmonary Arterial Hypertension

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 RCCS-M (03)]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cardiovascular;Dietary Supplements;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Nutrition;Precision Medicine;Prevention

ORG_CITY: BATON ROUGE

ORG_NAME: LSU PENNINGTON BIOMEDICAL RESEARCH CTR

ORG_STATE: LA

PHR: PROJECT NARRATIVE There is no one-size-fits-all diet for cardiovascular disease risk prevention and healthy aging. Uncovering factors that are responsible for the interindividual variability to dietary interventions will contribute to the fast- evolving field of personalized nutrition. This novel mentored F32 postdoctoral training grant is designed to understand whether diet quality impacts cardiometabolic health outcome variability to 2 years of a calorie restriction dietary intervention, and whether we can determine the best dietary pattern for optimal cardiometabolic health.

PI_NAMEs: WOOLF, EMILY KATLYN (contact)

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TERMS: Adherence;Adult;Affect;Age;Aging;aging related;Artificial Intelligence;Automobile Driving;Biological Markers;Biomarker of Dietary Intake;Blood;blood lipid;Blood Pressure;Caloric Restriction;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;career;Clinical;Clinical Nutrition;Clinical Trials;Consumption;Control Groups;Data;design;Diet;dietary;Dietary Fiber;Dietary Intervention;Dietary Practices;dietary restriction;Eating;Fasting;fasting glucose;Fishes;Food;Fruit;Glucose;Goals;Grain;Grant;Health;healthy aging;Healthy Eating;Hunger;improved;Incidence;indexing;Individual;Inflammation;Inflammatory;Insulin;Intake;inter-individual variation;Intervention;Intervention Trial;large datasets;Learning;learning strategy;life span;Machine Learning;machine learning method;Malnutrition;Measurable;Measures;Mentors;Metabolic;metabolomics;middle age;Morbidity - disease rate;mortality;novel;novel strategies;Nutrient;Nutritional;Nutritional Study;Nuts;Outcome;Oxidative Stress;Participant;Pathway interactions;Patient Self-Report;Pattern;personalized nutrition;Persons;Physiological;Plasma;Play;Population;post-doctoral training;precision nutrition;predicting response;predictive modeling;Prevention;primary outcome;Proteins;Public Health;Randomized;Recommendation;Records;Research Personnel;Research Project Grants;response;Risk Factors;Role;Satiation;Science;secondary outcome;skills;Statistical Data Interpretation;Statistical Methods;Techniques;Training;Treatment Efficacy;Urine;Vegetables;VO2max

PROJECT_TITLE: Examining dietary and metabolomics patterns on cardiometabolic outcome variability in response to calorie restriction


NIH_SPENDING_CATS: Cancer

ORG_CITY: AMES

ORG_NAME: IOWA STATE UNIVERSITY

ORG_STATE: IA

PHR: Project Narrative The research proposed in this application is relevant to human health because the studies will determine how T cell responses are tuned in response to different levels of stimulation. T cells are an important arm of the immune response that protect against viral and bacterial infections and have the potential to kill tumor cells. Continued improvement of T cell based therapeutic strategies demands a molecular level understanding of how T cells interpret and react to the stimuli they encounter during normal infections and in cancer. The work proposed in this project aligns with the NIH mission to “seek fundamental knowledge about the nature and behavior of living systems” for the improvement of human health.

PI_NAMEs: ANDREOTTI, AMY H (contact);BERG, LESLIE JOAN

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: Affinity;Amino Acids;Antibodies;Antigens;Antitumor Response;arm;Autoimmune Diseases;Autoimmunity;Automobile Driving;Avidity;B-Cell Antigen Receptor;Bacterial Infections;Behavior;Binding;Biochemical;Biological Assay;Catalysis;CD28 gene;CD3 Antigens;CD8-Positive T-Lymphocytes;Cell Differentiation process;Cell Physiology;Cellular Immunology;Charge;Chimeric Proteins;clinical efficacy;Code;Complex;Cytokine Receptors;Data;Defect;density;Development;Disease;DNA Sequence Alteration;Effector Cell;emt protein-tyrosine kinase;experimental study;Family;Funding;gain of function;Gene Expression;Gene Expression Profile;Genes;Health;Hematologic Neoplasms;Hemophagocytic Lymphohistiocytoses;Herpesviridae Infections;Hodgkin Disease;Human;human data;human disease;Human Herpesvirus 4;Immune response;Immunity;Impairment;improved;Infection;insight;Interleukin-2;Knowledge;Letters;Ligands;Link;Longevity;Malignant Neoplasms;Mediating;Membrane;Memory;Mission;Modification;Molecular;Mutagenesis;Mutation;Nature;neoplastic cell;Oncogenic;Organism;Outcome;Pathway interactions;Patients;Peptide/MHC Complex;Peripheral;PH Domain;Phospholipids;Phosphorylation;Phosphotransferases;Point Mutation;prevent;Process;Proline;Protein Tyrosine Kinase;Reaction;Receptor Signaling;Regulation;Research;response;Role;Sarcoidosis;SH3 Domains;Signal Pathway;Signal Transduction;src-Family Kinases;Stimulus;structural biology;Structure;SYK gene;T cell response;T cell therapy;T-Cell Activation;T-Cell Development;T-Cell Lymphoma;T-Lymphocyte;TEC Protein Tyrosine Kinase;Therapeutic;tool;tumorigenesis;Tyrosine;Tyrosine Kinase Domain;United States National Institutes of Health;Variant;Virus Diseases;Work

PROJECT_TITLE: Structural Studies of a T cell Specific Tyrosine Kinase

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IIDA-Y (02)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Gene Therapy;Genetics;Immunotherapy;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: Project Narrative: Despite numerous pediatric and adult cancers displaying Caspase-8 mutations, polymorphisms, and downregulation, little is known about how Caspase-8 in the tumor or tumor microenvironment affects anticancer immunity. These studies herein will expand upon preliminary data showing alterations in T cell activation and tumor growth dependent on Caspase-8 signaling by elucidating apoptotic and non-canonical inflammatory roles of Caspase-8 including potential implications for emerging CAR-T cell immunotherapies. Understanding the numerous roles of Caspase-8 in modulating tumor growth, immune response, and CAR-T cell efficacy may help to understand its frequent alteration in human cancers, identify pathways for targeting these Caspase-8-altered tumors directly, and identify therapeutic relevance for current therapies/immunotherapies.

PI_NAMEs: SHAW, JEREMY JOSEPH PORTER (contact)

PROGRAM_OFFICER_NAME: JAKOWLEW, SONIA B

PROJECT_TERMS: Ablation;Adult;Affect;Animals;anti-cancer;Apoptotic;Biological Assay;Bone Marrow;Bone Marrow Transplantation;Cancer Biology;cancer cell;Cancer cell line;cancer type;CAR T cell therapy;career;CASP8 gene;CD276 gene;Cell Death;Cell Death Induction;cell killing;Cell Physiology;Cells;Cellular biology;Cessation of life;Childhood;chimeric antigen receptor T cells;Clinical Trials;Colon Carcinoma;Complex;cytokine;Cytokine Signaling;cytotoxic;Data;Down-Regulation;effector T cell;Environment;Evaluation;exhaustion;experience;Flow Cytometry;Funding;Generations;Genes;Genetic Polymorphism;Goals;Growth;Human;Immune;immune cell infiltrate;immune imaging;Immune response;Immune signaling;Immune system;Immunologics;Immunology;Immunology procedure;Immunooncology;Immunotherapy;immunotherapy trials;improved;In Vitro;in vivo;Incubated;Inflammasome;Inflammatory;Institution;Interferons;International;Invaded;Journals;Knockout Mice;Knowledge;Literature;Lymphocyte;Lymphoid;Macrophage;Malignant Breast Neoplasm;Malignant Neoplasms;Manuscripts;Measures;Medulloblastoma;meetings;Microscopy;Mus;Mutate;Mutation;Myelogenous;neoplastic cell;Neuroblastoma;overexpression;Pathway interactions;Peptides;Postdoctoral Fellow;Preparation;prevent;Production;Proliferating;Proteins;Publications;Resistance;response;Role;Saint Jude Children's Research Hospital;Signal Pathway;Signal Transduction;skills;Solid Neoplasm;Stimulator of Interferon Genes;Stromal Cells;symposium;T-Cell Activation;T-Lymphocyte;Techniques;Therapeutic;Tissues;Training;tumor;tumor growth;Tumor Immunity;tumor microenvironment;Viral Vector;Work;Writing

PROJECT_TITLE: THE FUNCTION OF CASPASE-8 IN CANCER, ANTI-CANCER IMMUNITY, AND CAR-T CELL FUNCTION

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09C-Z (22)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Digestive Diseases;Esophageal Cancer;Orphan Drug;Rare Diseases;Stomach Cancer

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Gastric cancer is a leading cause of cancer deaths worldwide with a median survival of approximately 6 months for patients diagnosed with advanced disease. For some patients with gastric cancer, their tumor is driven by genetic alterations in fibroblast growth factor receptor 2 (FGFR2) and early clinical data shows promising results for FGFR2-directed therapies. In this proposal, we will use innovative mouse models of FGFR2-driven gastric cancer to test new types of enhanced FGFR2 targeting antibodies and determine how FGFR2-driven gastric tumors become resistant to these and other FGFR2 therapeutics.

PI_NAMEs: EL-BARDEESY, NABEEL ;RYEOM, SANDRA  (contact);SELLERS, WILLIAM R

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Admixture;advanced disease;Antibodies;Antibody-drug conjugates;antitumor effect;Attenuated;Autopsy;Avidity;Biopsy;Cancer Etiology;Cell Line;cell type;Cessation of life;chemotherapy;Clinical;Clinical Data;Clinical Trials;Combined Modality Therapy;Data;Diagnosis;dimer;Disease;Electroporation;Engineering;Epitopes;ERBB2 gene;experimental study;Extracellular Domain;FGF2 gene;Fibroblast Growth Factor 2 Overexpression;fibroblast growth factor 6;Fibroblast Growth Factor Receptor 2;Fibroblast Growth Factor Receptors;gastroesophageal adenocarcinoma;gastroesophageal cancer;Gene Amplification;Gene Fusion;Heterogeneity;high-throughput drug screening;Imatinib;Immune;Immune checkpoint inhibitor;Immune system;Immunocompetent;improved;In Vitro;in vivo;in vivo Model;inhibitor;innovation;Intrahepatic Cholangiocarcinoma;kinase inhibitor;Ligands;malignant stomach neoplasm;Mediating;Modality;Modeling;Monoclonal Antibodies;mouse model;Mutation;Nature;neoplastic cell;novel;Organoids;overexpression;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Phase II Clinical Trials;phase II trial;Phosphotransferases;prevent;pro-apoptotic protein;Prognosis;Progression-Free Survivals;Proteins;Randomized;receptor;Resistance;resistance mechanism;resistance mutation;response;Role;Sampling;SCID Mice;screening;Signal Transduction;small molecule;small molecule inhibitor;Specimen;standard of care;Stomach;Stomach Neoplasms;synergism;Testing;Therapeutic;Therapeutic antibodies;Trastuzumab;tumor;Tumor Cell Line;Tyrosine Kinase Inhibitor;Wild Type Mouse;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Targeting FGFR Alterations in Gastroesophageal Cancer

STUDY_SECTION: DMPC

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology C Study Section[DMPC]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Disability Research;Hearing Loss;Mental Health;Neurosciences

ORG_CITY: WASHINGTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: GALLAUDET UNIVERSITY

ORG_STATE: DC

PHR: This research project on the impact of American Sign Language (ASL) fluency on spatial cognition in Deaf individuals contributes to the fundamental knowledge of development and its application to enhance health. By examining the direct correlation between ASL proficiency and spatial reasoning skills, the study seeks to provide targeted insights for developing more effective cognitive interventions and diagnostic tools. These insights are particularly relevant for enhancing cognitive health strategies and educational approaches for the Deaf community, potentially leading to improved health outcomes and quality of life for Deaf individuals.

PI_NAMEs: SCHWENK, MELODY FAITH (contact)

PROGRAM_OFFICER_NAME: SCHURMAN, JACLYN REBECCA

PROJECT_TERMS: Address;American Sign Language;Aptitude;Area;Auditory;behavior measurement;Brain;Categories;Child;Cognition;Cognitive;cognitive ability;cognitive benefits;Cognitive deficits;cognitive enhancement;cognitive task;Collaborations;Communication;Communities;Cues;Data Correlations;deaf;Development;Diagnostic;diagnostic tool;Education;Electroencephalography;Elements;Environment;Exhibits;experience;Facial Expression;Hand;Health;Healthcare;healthy aging;Hearing;improved;Individual;information processing;insight;Intervention;Knowledge;Language;Language Comprehension Tests;language processing;Life;Linguistics;Link;Location;Maps;Motor;Movement;Nature;neural;neural patterning;Neurocognitive;neuromechanism;Neuropsychology;Oral;Outcome;Participant;Pattern;Performance;Personal Satisfaction;Persons;perspective taking;Population;Population Heterogeneity;practical application;Process;psychologic;Public Health;Quality of life;reading difficulties;recruit;Research;Research Personnel;Research Project Grants;Research Proposals;response;Sensory;Shapes;Short-Term Memory;Sign Language;skills;Space Perception;spatial relationship;Standardization;temporal measurement;Therapeutic;Translating;Visuospatial;way finding;Writing

PROJECT_TITLE: American Sign Language and Spatial Cognition Skills: A Neurocognitive Study Using EEG and Standardized Neuropsychological Assessments

STUDY_SECTION_NAME: Special Emphasis Panel[ZDC1 SRB-N (35)]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Stomach Cancer

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE This project aims to dissect the early molecular and cellular events in paligenosis, a multi-stage repair mechanism that recruits differentiated cells back into the cell cycle to facilitate tissue regeneration in response to injury. The study will specifically examine the role of the kinase PERK, and rough endoplasmic reticulum degradation by autophagy in the early stages of paligenosis. The outcomes of this research could identify new therapeutic targets for potentially blocking metaplasia in diverse settings where precancerous lesions arise from paligenosis of mature, differentiated cells.

PI_NAMEs: NGUYEN, THANH  (contact)

PROGRAM_OFFICER_NAME: RIVERS, ROBERT C

PROJECT_TERMS: activating transcription factor 3;Acute;Adult;Agonist;arm;attenuation;Autophagocytosis;Back;biological adaptation to stress;Body System;cancer risk;Cell Cycle;Cell Differentiation process;cell regeneration;Cells;Chief Cell;Chronic;Coin;Collaborations;Complex;Dangerousness;Data;Dedications;DNA Damage;DNA Sequence Alteration;Dose;Early identification;EIF-2alpha;Endoplasmic Reticulum;endoplasmic reticulum stress;Environment;Event;experimental study;gastric carcinogenesis;gastric corpus;Gastrointestinal tract structure;gene network;Genes;Genetic Transcription;Guanosine Triphosphate;Homeostasis;Hydroxychloroquine;Inflammation;inhibitor;Initiator tRNA;Injury;insight;Knowledge;Lesion;Lysosomes;Malignant Neoplasms;Membrane;Membrane Proteins;Metaplasia;Modeling;Molecular;Monitor;Morphology;mouse model;mRNA Translation;Mus;new therapeutic target;Organ;Organelles;Outcomes Research;paligenosis;Pathway interactions;PERK kinase;Pharmaceutical Preparations;Phosphorylation;Phosphotransferases;premalignant;Process;progenitor;programs;promoter;Protein Biosynthesis;Proteins;recruit;Regulation;repaired;response biomarker;response to injury;Ribosomes;Role;Rough endoplasmic reticulum;Secretory Cell;sensor;Signal Transduction;Smooth Pursuit;spasmolytic polypeptide;stem cell proliferation;stem cells;Stomach;Stress;stressor;Structure;Swelling;Tamoxifen;Testing;Time;tissue regeneration;Tissues;Translation Initiation;Translational Repression;Translations;Transmission Electron Microscopy;Western Blotting;Wing;Work

PROJECT_TITLE: Investigating the roles and dynamics of the endoplasmic reticulum during paligenosis and metaplasia formation

STUDY_SECTION_NAME: Fellowships in Digestive Diseases and Nutrition[DDK-F]


NIH_SPENDING_CATS: Emerging Infectious Diseases;Genetics;Infectious Diseases;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: DAVIS

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative Inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) is seen in 1-2% of European and US populations, and 0.6% of populations in Japan. Currently, there are no in vitro tissue culture models that capture naturally occurring iciHHV-6 reactivation and that is important to understand the biology and pathology of iciHHV- 6. Here, we generate iciHHV-6 patient-derived induced pluripotent stem cells and utilize them to explore the molecular mechanisms of iciHHV-6 reactivation from integrated genome.

PI_NAMEs: IZUMIYA, YOSHIHIRO  (contact);YOSHIKAWA, TETSUSHI

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: 2 year old;Acute;Address;Affect;Age;Angina Pectoris;Antineoplastic Agents;bioinformatics tool;Biological;Biology;cell bank;Cell Differentiation process;Cell Line;Cell Lineage;Cell model;cell type;Cells;Central Nervous System Diseases;Chromosomes;Clinical;clinically relevant;Collaborations;cytokine;Development;Direct Repeats;Disease;Encephalitis;Etiology;European;Event;Funding;Future;Gene Expression;Generations;Genetic Recombination;Genetic Transcription;Genome;Germ Lines;graft vs host disease;Health;Hematopoietic;Hematopoietic Stem Cell Transplantation;HHV-6A;HHV-6B;Human;Human Herpesvirus 6;Immunocompromised Host;In Situ;In Vitro;in vitro Model;Individual;induced pluripotent stem cell;Infection;Inherited;International;Japan;Knowledge;Length;Ligands;Limbic Encephalitis;Mediating;medical schools;Modeling;Molecular;Molecular Analysis;Mucous body substance;nerve stem cell;Nervous System Disorder;neural;Neurons;neurovirulence;Nose;Outcome;Pathology;patient derived induced pluripotent stem cells;Patients;Peripheral Blood Mononuclear Cell;Persons;Physiological;Population;Pre-Eclampsia;Pregnancy;racial diversity;Research;Research Design;Research Personnel;Resources;Respiratory System;response;Risk;RNA;Saliva;Side;Signal Transduction;single cell sequencing;small hairpin RNA;Specific qualifier value;Spontaneous abortion;Stains;Stimulus;Tandem Repeat Sequences;telomere;Temporal Lobe Epilepsy;Testing;therapeutic development;tissue culture;Tissues;Transcript;transcriptome sequencing;transcriptomics;Universities;Viral;Viral Genome;virology;Virus;Virus Integration

PROJECT_TITLE: Studies on Inherited Chromosomally Integrated HHV-6 with Patient-derived Induced Pluripotent Stem Cells

STUDY_SECTION: VDT

STUDY_SECTION_NAME: Viral Dynamics and Transmission Study Section [VDT]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Rare Diseases;Vaccine Related

PHR: Narrative Henipaviruses that can spread from animal to human and between humans have caused repeated outbreaks with high case fatality rates. To counteract the growing threat posed by the expanding henipavirus members, we will structurally and functionally characterize their surface glycoproteins G and F and to identify sites of vulnerability using protective antibodies. The result of this study will pave the way for future development of effective vaccine and therapeutics against these viruses.

PI_NAMEs: XU, KAI  (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Acute;Animals;Antibodies;bat-borne;Biological;Biological Assay;Camels;Case Fatality Rates;Categories;Category C pathogen;Cell fusion;Cells;Coupled;cross reactivity;Cryoelectron Microscopy;design;Development;Disease Outbreaks;Distant;Electron Microscopy;Encephalitis;Epitope Mapping;Epitopes;Family;Future;future pandemic;global health;glycoprotein G;Glycoproteins;Goals;GTP-Binding Proteins;Head;Hendra Virus;Henipavirus;Human;Immunotherapeutic agent;Incidence;insight;Mediating;member;Membrane Fusion;Membrane Glycoproteins;Methods;Molecular Conformation;Monoclonal Antibodies;monomer;mouse model;murine antibody;Mus;Mutagenesis;Names;nanobodies;National Institute of Allergy and Infectious Disease;Negative Staining;neutralizing antibody;neutralizing monoclonal antibodies;Nipah Virus;pandemic disease;pandemic preparedness;Paramyxovirus;Persons;Process;Property;Proteins;Protomer;prototype;rational design;Reagent;receptor;recombinant virus;Reporting;Research;Resolution;respiratory;Risk;Role;Route;Safety;Sampling;screening;Site;spillover event;Structure;Surface;Therapeutic;therapeutic development;tool;transmission process;Tropism;Vaccine Design;vaccine-induced antibodies;Vaccines;Viral;Virion;Virus;Work;Zoonoses

PROJECT_TITLE: Structure, function, and antigenicity of emerging henipavirus surface glycoproteins

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


NIH_SPENDING_CATS: Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Orphan Drug;Prevention;Rare Diseases

PHR: Narrative Zoonotic lyssaviruses causing acute rabies encephalitis diseases are responsible for the death of over 59,000 people each year worldwide. Current treatments and vaccines are effective only towards a subset of lyssavirus members due to the high genetic and antigenic diversity. We propose to target a conserved site of viral vulnerability to develop pan-lyssavirus nanobody therapeutics against both circulating and emerging lyssaviruses.

PROJECT_TERMS: Acute;Adopted;Affect;Affinity;Antibodies;Antigen-Antibody Complex;Antigenic Diversity;Antigens;Bacteriophages;Binding;Biochemical;Biological Assay;Camels;Central Nervous System;Cessation of life;Clinical;Communicable Diseases;design;design and construction;Development;Disease;Disease Progression;Dose;Electron Microscopy;Encephalitis;Epitopes;extracellular;Family;flexibility;Future;Generations;Genetic Variation;glycoprotein G;Glycoproteins;GTP-Binding Proteins;Homologous Protein;Human;human monoclonal antibodies;Immune;Immunize;Immunoglobulins;Immunotherapeutic agent;improved;in vivo;Libraries;Lyssavirus;Mammals;Maps;member;Modality;Modeling;Molecular Conformation;Monoclonal Antibodies;mouse model;nanobodies;neutralizing antibody;novel;Persons;PH Domain;Phage Display;prevent;Prophylactic treatment;protective efficacy;protein structure;Proteins;Rabies;Rabies Vaccines;Reporting;Rhabdoviridae;screening;segregation;Sequence Analysis;Site;structural biology;Structure;Surface;Tertiary Protein Structure;Therapeutic;Therapeutic Agents;Therapeutic antibodies;therapeutically effective;Vaccines;Viral;Virion;Virus;X-Ray Crystallography;Zoonoses

PROJECT_TITLE: Targeting glycoprotein (G) domain-III for pan-lyssavirus nanobody therapeutics


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Chronic Pain;Fentanyl Misuse and Addiction;Neurosciences;Opioid Misuse and Addiction;Opioids;Pain Research;Substance Misuse

ORG_CITY: SAINT LOUIS

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Pain can serve as a driving force for the development of both alcohol and opioid use disorders, but the relationships between pain, alcohol, and opioid use and the neurobiological mechanisms underlying these relationship are understudied and poorly understood. This proposal aims to address this gap by utilizing a mouse model of intravenous self-administration to examine the involvement of a novel dynorphinergic extended amygdala circuit in pain- and fentanyl abstinence- mediated binge-like alcohol drinking, and whether binge alcohol modulates reinstatement of fentanyl seeking. The results of this work will fill a gap in knowledge in the fields of addiction and pain research and will provide a platform for immensely valuable training as a future independent scientist in the alcohol research field.

PI_NAMEs: CUCINELLO-RAGLAND, JESSICA  (contact)

PROGRAM_OFFICER_NAME: EGLI, MARK

PROJECT_TERMS: Abstinence;addiction;Address;Alcohol consumption;Alcohol dependence;alcohol effect;alcohol research;alcohol use disorder;Alcohols;Amygdaloid structure;Animals;Automobile Driving;Behavior;Behavioral;behavioral response;Brain;Cell Nucleus;chronic pain;Clinical;Cognitive;comorbidity;Complex;Conflict (Psychology);Cues;Darkness;Data;Development;disability;Disinhibition;drinking;driving force;Dynorphins;endogenous opioids;experience;Exposure to;Female;Fentanyl;fentanyl seeking;fentanyl use;Fiber;Frequencies;Freund's Adjuvant;Functional disorder;Funding;Future;Genetic Techniques;Goals;Health;high risk;Individual;inflammatory pain;Intravenous;kappa opioid receptors;Knowledge;Ligands;Maintenance;male;Measures;Mechanics;Mediating;Modeling;Motivation;mouse model;Mus;negative affect;neurobiological mechanism;Neurobiology;Neurons;Nociception;Nose;novel;Nucleus Accumbens;Opiate Addiction;Opioid;opioid misuse;opioid use;opioid use disorder;Outcome;Pain;pain behavior;pain chronification;pain inhibition;pain relief;Pain Research;Persistent pain;Photometry;polysubstance use;pre-clinical;Quality of life;Rattus;Receptor Signaling;Reporting;Research;Research Personnel;Rewards;Role;Scientist;Self Administration;sex;Sex Differences;Signal Transduction;substance use;Substance Use Disorder;System;Testing;Time;Training;Viral;wireless;Work

PROJECT_TITLE: Role of a novel dynorphinergic extended amygdala circuit in pain- and fentanyl abstinence- facilitated alcohol drinking

STUDY_SECTION_NAME: Special Emphasis Panel[ZAA1 GG (32)]


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Neurosciences;Substance Misuse

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE The neuroscientific understanding of alcohol use disorder (AUD) has advanced tremendously over the past three decades. However, translation from preclinical models to clinical studies lags behind the evolving neuroscience literature. Given the limited knowledge about how prominent neurobiological models of AUD translate to human samples, this proposal seeks to test (1) the potential interaction effect of the allostatic and incentive-sensitization models in a human sample, (2) the predictive effect of these models, and (3) the demographic moderators (e.g., biological sex) of the relationship between the allostatic and incentive- sensitization models by collecting daily diary assessments of mood, craving, and cue exposure over a 14-day period and at 4, 8, and 12-weeks post daily diary assessment.

PI_NAMEs: BASKERVILLE, WAVE-ANANDA  (contact)

PROGRAM_OFFICER_NAME: SENEVIRATNE, CHAMINDI

PROJECT_TERMS: addiction;Address;Alcohol consumption;alcohol craving;alcohol cue;alcohol effect;alcohol use disorder;Alcoholic beverage heavy drinker;Alcohols;biological sex;Clinical;clinical application;Clinical Research;craving;cue reactivity;Cues;demographics;Development;diaries;drinking;Environment;experience;Exposure to;Female;follow up assessment;follow-up;Fostering;Heavy Drinking;Human;incentive salience;Incentives;Individual;innovation;interest;Knowledge;Laboratories;Literature;Mentors;Methodology;Methods;Modeling;Moods;Motivation;multilevel analysis;National Research Service Awards;negative affect;negative mood;Negative Reinforcements;neural;Neurobiology;Neurosciences;next generation;Outcome;pre-clinical;Pre-Clinical Model;pre-doctoral;precision medicine;Process;Reporting;Research;Research Personnel;Rewards;Sampling;Scientist;Stimulant;Testing;theories;therapy development;Time;Training;Translating;Translational Research;translational scientist;Translations;Visit;Withdrawal

PROJECT_TITLE: Testing Neurobiological Models of Alcohol Use Disorder Through Real World Cue Reactivity and Mood


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Drug Abuse (NIDA only);Electronic Nicotine Delivery Systems;Harm Reduction for Substance Misuse;Lung;Lung Cancer;Prevention;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: CHARLESTON

ORG_DEPT: PSYCHIATRY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Project Narrative This prospective cohort study will examine the natural course of dual use (combustible and electronic cigarette), as compared to exclusive smoking and exclusive e-cigarette use. Using a multi-method assessment approach, the aims are to compare dynamic patterns of use within and across groups, as well to identify the unique and combined patterns of dual use that best predict eventual quitting of combustible cigarettes. Study results will have clinical and regulatory implications for fast growing number of alternative tobacco products and those who (co-)use them.

PI_NAMEs: CARPENTER, MATTHEW J (contact);KLEMPERER, ELIAS M

PROGRAM_OFFICER_NAME: KIMMEL, HEATHER L

PROJECT_TERMS: Abstinence;Acute;Adult;Behavior;Biological;cancer prevention;Characteristics;Chronic;Cigarette;Cigarette Smoker;cigarette smoking;cigarette user;Classification;Clinical;cohort;Cohort Studies;combustible cigarette;Complex;Data;Decision Making;design;Devices;diaries;Electronic cigarette;electronic cigarette use;electronic cigarette user;Equation;Evaluation;follow-up;Grain;Graph;Harm Reduction;Health;Incidence;Individual;Knowledge;Malignant Neoplasms;marijuana use;Marketing;Methods;Modeling;mortality;national surveillance;Natural History;next generation;Nicotine;Nicotine Dependence;non-cigarette tobacco product;novel;Outcome;Participant;Pattern;Policies;polytobacco use;Population;Population Study;Prevalence;Prevention Research;programs;Proliferating;prospective;Prospective, cohort study;Public Health;Publishing;randomized, clinical trials;Recording of previous events;recruit;Research;Research Design;Risk;Sampling;Science;secondary analysis;Smoke;Smoker;Smoking;smoking cessation;Surveys;Time;Tobacco;tobacco products;Tobacco use;tobacco user;Toxicant exposure;vaping

PROJECT_TITLE: Dual use of combustible and electronic cigarettes: A fine-grained naturalistic cohort study to investigate dynamic use patterns and trajectories that lead to smoking cessation

STUDY_SECTION: IPTA

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


NIH_SPENDING_CATS: Contraception/Reproduction;Hypertension;Kidney Disease;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Women's Health Research

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

ORG_STATE: CA

PHR: Project Narrative To study the mechanisms of increased risk of preeclampsia in women with a history of impaired kidney function, we will characterize pregnancy phenotypes in mouse models of renal insufficiency and will specifically study how loss of renal reserve leads to preeclampsia.

PI_NAMEs: KARUMANCHI, S. ANANTH (contact)

PROGRAM_OFFICER_NAME: ILEKIS, JOHN V

PROJECT_TERMS: Abnormal placentation;Acute Renal Failure with Renal Papillary Necrosis;adverse outcome;adverse pregnancy outcome;Angiogenesis Inhibitors;Angiogenic Proteins;Arteries;Biological Availability;Biological Markers;Biology;Blood flow;blood flow measurement;Blood Plasma Volume;Blood Pressure;Chronic Kidney Failure;Clinical Research;Complement;Defect;design;Development;Diagnosis;Down-Regulation;Etiology;experimental study;fetal;Formulation;Functional disorder;Gene Expression Profile;Glomerular Filtration Rate;Goals;high risk population;Human;Hypertension;Impaired Renal Function;Impairment;improved;in vivo;innovation;Intervention;Ischemia;Kidney;kidney allograft;Kidney Diseases;kidney dysfunction;Kidney Failure;Kynurenine;Late pregnancy;Litter Size;Mass Spectrum Analysis;Measurement;Measures;Mediating;medical complication;Metabolic;Metabolism;Methods;Modeling;Monitor;mouse model;Mus;Nicotinamide adenine dinucleotide;nicotinamide-beta-riboside;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Phenotype;Physiology;Placenta;Placentation;Plasma;Play;Pre-Eclampsia;Pregnancy;Pregnancy Complications;pregnant;Proteinuria;Publishing;receptor;Recording of previous events;Renal function;Risk;Risk Factors;Role;Secondary to;Spiral Artery of the Endometrium;Syndrome;Testing;Third Pregnancy Trimester;Tissues;transcriptomics;Translating;Tryptophan;Uterus;Vascular Endothelial Growth Factor Receptor-1;Weight;Wild Type Mouse;Woman

PROJECT_TITLE: Impaired Renal Reserve and Preeclampsia

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bipolar Disorder;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Prevention;Serious Mental Illness;Social Determinants of Health

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: PROJECT NARRATIVE Ventral prefrontal-limbic networks, which are implicated in bipolar disorder and important for emotional regulation, undergo significant maturation during adolescence and young adulthood, but little is understood about the neurodevelopmental patterns within these networks which may predispose some youth to onset of the condition. By investigating the maturation of ventral prefrontal-limbic networks during negative psychosocial stress in youth with and without an increased familial risk of bipolar disorder I, we hope to better understand neurodevelopmental pathways associated with early emotional dysregulation and vulnerability to the condition. Understanding the neuropathological changes that occur during this pivotal period of social-emotional development is an essential first step towards implementing earlier interventions to mitigate long-term illness and disability well before the onset of bipolar disorder and more serious secondary progressive outcomes.

PI_NAMEs: SIEGEL-RAMSAY, JENNIFER E (contact)

PROGRAM_OFFICER_NAME: CORNELL, ASHLEY ROSE

PROJECT_TERMS: Adolescence;Adolescent;adolescent brain development;Adult;Affect;Age;Amygdaloid structure;Anterior;Area;Attenuated;Award;Bipolar Disorder;Bipolar I;Brain;brain control;Brain imaging;Brain region;career;career development;Clinical;clinical diagnosis;Cognitive;cohort;Corpus striatum structure;Cues;Data;Development;Diagnosis;disability;Disease;disorder risk;Distress;Early Intervention;emotion dysregulation;emotion regulation;Emotional;Emotions;Exclusion;Exhibits;Family;Family history of;Fellowship;follow-up;functional disability;Future;Goals;Grant;hands on research;high risk;high risk population;Hypersensitivity;improved outcome;Individual;Insula of Reil;Intervention;Knowledge;Lateral;Liquid substance;Measures;Medial;Mental Health;mood symptom;Moods;mortality risk;Neurobiology;neurodevelopment;neuroimaging;neuropathology;Onset of illness;Outcome;Participant;Pathway interactions;Pattern;peer;peer influence;Physiological;Predisposition;Prefrontal Cortex;progressive neurodegeneration;promote resilience;Psychosocial Stress;psychosocial stressors;Publications;Recording of previous events;Regulation;Research;Research Project Grants;resilience;response;Risk;Signal Transduction;social;Social Development;social exclusion;social influence;Social Interaction;stress resilience;Techniques;Testing;Thalamic structure;Training;virtual;Work;young adult;Youth

PROJECT_TITLE: Neurodevelopmental Patterns of Social Reactivity in Youth at Increased Familial Risk for Bipolar I Disorder

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01A-V (20)]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Clinical Research;Data Science;Genetics;Human Genome;Immunotherapy;Nanotechnology;Orphan Drug;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_DEPT: OBSTETRICS & GYNECOLOGY

PHR: PROJECT NARRATIVE High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive subtype of tubo-ovarian cancers. This project will comprehensively elucidate the landscape of alternative mRNA processing and the resulting full-length transcript and protein isoform variation in HGSOC, with the objective of discovering novel immunotherapeutic targets. Our research seeks to find new targets and therapeutic reagents for adoptive T-cell therapy and evaluate their efficacy in pre-clinical models of HGSOC.

PI_NAMEs: MEMARZADEH, SANAZ  (contact);XING, YI

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Affect;Alleles;anti-cancer;antigen-specific T cells;Antigens;Benchmarking;Big Data;biobank;Biological;Biological Assay;Cancer Biology;cancer cell;cancer therapy;Categories;Cell surface;Cells;Cellular immunotherapy;cellular targeting;clinically relevant;Clonality;Co-Immunoprecipitations;cohort;computational platform;cytotoxicity;Data;data integration;Data Set;design;Development;Developmental Cell Biology;Diagnosis;directed differentiation;Disease;efficacy study;Epitopes;ethnic diversity;Generations;genomic RNA;Heterogeneity;HLA-A gene;Human;Immune system;Immunooncology;Immunotherapeutic agent;Immunotherapy;In Vitro;in vivo;interest;Length;Malignant neoplasm of ovary;Malignant Neoplasms;Messenger RNA;Molecular;multidisciplinary;Multiomic Data;multiple omics;nanopore;Normal tissue morphology;novel;Organoids;Ovarian Serous Adenocarcinoma;patient derived xenograft model;Patients;Pediatric Hospitals;Peptides;Philadelphia;Platinum;pluripotent stem cell differentiation;pre-clinical;Pre-Clinical Model;preclinical efficacy;Primary Neoplasm;Program Development;programs;Protein Isoforms;Proteins;Proteome;Reagent;Recurrent disease;Relapse;Research;Resistance;Resources;RNA;Sampling;single-cell RNA sequencing;Somatic Mutation;Source;Specificity;Specimen;T cell therapy;T-Cell Activation;T-Cell Receptor;T-Cell Receptor Therapy;T-Lymphocyte;T-Lymphocyte Epitopes;targeted treatment;Testing;Therapeutic;therapy outcome;Thymus Gland;Tissues;tool;Transcript;transcriptome;transcriptome sequencing;transcriptomics;Treatment Efficacy;tumor;Tumor Antigens;Tumor Biology;tumor heterogeneity;tumor immunology;Tumor Tissue;Variant

PROJECT_TITLE: Targeting alternative isoform variation for TCR discovery in platinum-resistant ovarian cancer

STUDY_SECTION: CIC

STUDY_SECTION_NAME: Cellular Immunotherapy of Cancer Study Section[CIC]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cardiovascular;Clinical Research;Heart Disease;Neurosciences;Pediatric;Physical Activity;Prevention;Sleep Research

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE Despite often being associated with old age, cardiovascular disease is on the rise in younger populations; indeed, cardiovascular risk begins to accumulate in early life, with disease progression strongly influenced by health behaviors. The present study will use ambulatory assessment technologies and novel statistical methods to investigate the interactive and synergistic effects of 24-hour behaviors (physical activity, sedentary behavior, sleep) and circadian rhythm on primordial (i.e., early subclinical) indicators of cardiovascular risk within healthy young adults. Findings will be used to inform primordial prevention efforts to halt subclinical cardiovascular disease progression and develop tailored behavioral recommendations that apply to unique individuals’ everyday lives.

PI_NAMEs: LYONS, RACHEL CROSLEY (contact)

PROJECT_TERMS: Accelerometer;Activity Cycles;Address;Affect;Age;aged;Agreement;Algorithms;American Heart Association;Area;Behavior;Behavioral;Biological Markers;Calendar;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cardiovascular system;Characteristics;circadian;Circadian Rhythms;Clinic;Clinical;cohort;Consensus;Data;Data Collection;Development;Devices;Disease Outcome;Disease Progression;Ecological momentary assessment;emerging adult;evidence base;Exclusion;Fatigue;Fellowship;Fossils;Functional disorder;Funding;Future;Grant;Guidelines;Health behavior;Health behavior change;health care availability;health determinants;Hospitalization;Hour;human old age (65+);Hyperlipidemia;Hypertension;improved;Individual;innovation;Knowledge;Life;Light;Literature;Longitudinal Studies;Measures;Mentors;Mentorship;Methods;moderate-to-vigorous physical activity;Morbidity - disease rate;mortality;Movement;multilevel analysis;novel;Older Population;Participant;Patient Self-Report;Patients;Pattern;Persons;Physical activity;Physiological;Population;prevent;Prevention;Prevention strategy;Recommendation;Reporting;Research;Rest;Risk;Risk Factors;risk perception;Scientist;screening;sedentary;sedentary lifestyle;Series;Sleep;sleep behavior;Sleep Deprivation;Sleep Disorders;sleep quantity;smart watch;Sports;Statistical Data Interpretation;Statistical Methods;Stress;Stroke;synergism;Target Populations;Technology Assessment;theories;Time;Time Study;Training;United States National Institutes of Health;Variant;Wrist;young adult

PROJECT_TITLE: Within-person compositional analysis of 24-Hour Activity Cycle behaviors and circadian metrics related to cardiovascular disease.


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Orthopoxviruses;Rare Diseases

ORG_CITY: SAN ANTONIO

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: Project Narrative Elucidating the antiviral mechanisms of intracellular host restriction factors is essential for understanding viral replication and designing strategies against emerging pathogens. SAMD9 is a critical host restriction factor that poxviruses, including mpox, must overcome for productive replication. SAMD9 may also impact other viruses of the oral cavity including HPV and HSV-1. Understanding how SAMD9 regulates mpox infection will help develop effective antiviral strategies against future mpox outbreaks and will open new areas of investigation between SAMD9 and other viruses of the oral cavity. The ligand that induces SAMD9 activation and the domain involved in sensing infection will be studied.

PI_NAMEs: MORALES, MARISOL  (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: Address;Affinity;Amino Acids;anticodon nuclease;Area;Binding;Biochemical;Biological Assay;C-terminal;cell type;Cells;Complex;Cytoplasm;Cytoplasmic Tail;cytosolic receptor;Data;design;Disease Outbreaks;ds-DNA;emerging pathogen;Exanthema;experimental study;Flow Cytometry;Fluorescence Resonance Energy Transfer;Future;Generations;Herpesvirus 1;Homeostasis;Human Papillomavirus;Immune response;Immunity;In Vitro;in vitro Assay;Incubated;Individual;Infection;inhibitor;innovation;Investigation;Knowledge;Length;Leptin;Ligands;Location;Measures;Modeling;Molecular;Monkeypox;Monkeypox virus;Mutagenesis;mutant;Mutation;Nucleic Acid Binding;nucleic acid binding protein;Nucleic Acids;Oral;Oral cavity;Oral mucous membrane structure;Oral Pathology;Oropharyngeal;pathogen;pathogenic virus;Phase;Phenylalanine;Physiological;Poxviridae;Poxviridae Infections;Productivity;Protein Biosynthesis;Protein Synthesis Inhibition;Proteins;receptor;Recombinants;Research Personnel;Route;SAM Domain;sensor;Sequence Homology;Signal Transduction;Structure;Technical Expertise;Testing;Tonsillitis;Transfer RNA;transmission process;Vaccinia virus;Viral;Viral Genome;Viral Physiology;Viral Proteins;viral transmission;Virus;Virus Diseases;virus host interaction;Virus Replication;Work

PROJECT_TITLE: Characterization of a sensor domain for cytoplasmic nucleic acid in the antiviral factor, SAMD9

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07C-Y (20)]


FUNDING_MECHANISM: RESEARCH CENTERS

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Immunotherapy;Patient Safety;Precision Medicine;Prevention;Women's Health Research

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: PROJECT NARRATIVE – OVERALL The Stanford Cancer Institute (SCI) brings together researchers from across Stanford University with the goals of improving cancer prevention, detection, diagnosis, treatment, and outcomes for individuals and for populations, both within our region and in the world at large. The SCI has a compelling history of cancer discovery that has accelerated with the development of innovative new technologies, a strong focus on understanding the etiologies of cancers in individuals and in populations, a proven track record in implementing high impact clinical trials and a mission to translate findings to improve the care of cancer patients. With the support of the Cancer Center Support Grant, the SCI makes major contributions across the spectrum of research from basic discovery through clinical application to the population sciences that will enhance our understanding of disease processes, bring new diagnostic and therapeutic modalities to patients, facilitate risk assessment and prevention, and improve the overall outlook for individuals afflicted with or at risk for cancer.

PI_NAMEs: ARTANDI, STEVEN E (contact)

PROGRAM_OFFICER_NAME: BELIN, PRECILLA L

PROJECT_TERMS: Acceleration;Address;Adjuvant;Adjuvant Chemotherapy;Adjuvant Therapy;Animals;anti-cancer research;Antineoplastic Agents;Area;arm;base;Basic Science;Biological Assay;Biological Sciences;biomedical informatics;Biometry;breast cancer genomics;Breast Cancer Patient;Cancer Biology;cancer care;Cancer Center Support Grant;Cancer Detection;Cancer Etiology;Cancer health equity;cancer imaging;cancer immunotherapy;Cancer Patient;cancer prevention;cancer risk;cancer stem cell;CAR T cell therapy;Catchment Area;cell free DNA;Cells;chemotherapy;Clinical;clinical application;Clinical Data;Clinical Oncology;clinical practice;Clinical Protocols;Clinical Trials;Colon Carcinoma;community engagement;Community Outreach;Comprehensive Cancer Center;Data;data management;Detection;detection limit;detection method;Detection of Minimal Residual Disease;Development;Diagnosis;Disease;DNA;DNA Sequence Alteration;Doctor of Philosophy;drug discovery;Early Diagnosis;Early treatment;Engineering;Epidemiology;ERBB2 gene;Faculty;Flow Cytometry;follow-up;Funding;Genetic;Genomics;Goals;Guidelines;Hand;health equity;Hematologic Neoplasms;Human;Humanities;Image;imaging detection;Immunologic Monitoring;Immunology;improved;Individual;innovation;Investments;Leadership;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;Mammary Neoplasms;Measurable;Medicine;member;Methods;Mission;Modality;Modeling;Monitor;multidisciplinary;National Clinical Trials Network;new technology;novel diagnostics;novel therapeutics;Operative Surgical Procedures;Outcome;Patients;Peer Review;Phase;Phase II Clinical Trials;Physicians;Population;population based;population health;Population Heterogeneity;Population Sciences;Postoperative Period;predictive modeling;Prevention;Process;programs;Proteomics;Protocols documentation;Radiobiology;randomized trial;Recommendation;Recording of previous events;recruit;Recurrence;Relapse;Reporting;Research Personnel;Resected;Residual Neoplasm;Resource Sharing;Risk;Risk Assessment;Sampling;Schools;Science;Scientist;screening;side effect;Single Nucleotide Polymorphism;stem;Survival Rate;Systemic Therapy;Talents;technology development;Testing;Therapeutic;Time;Tissue Procurements;Training and Education;Translating;Translations;triple-negative invasive breast carcinoma;tumor;tumor DNA;Tumor-Derived;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: Stanford Cancer Institute

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Cancer Centers Study Section (A)[NCI-A]


ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

PHR: Project Narrative The proposed research employs a straightforward and highly reproducible Drosophila tumor model to investigate the involvement of polyploidy and sex dimorphism in tumor growth and progression. Successful execution of this study will enhance our understanding of intratumor ploidy heterogeneity and provide better strategies for cancer prevention and treatment that consider sex differences.

PI_NAMEs: DENG, WU-MIN  (contact)

PROGRAM_OFFICER_NAME: FINGERMAN, IAN M

PROJECT_TERMS: Aneuploidy;Apoptosis;cancer cell;cancer prevention;cancer stem cell;cancer therapy;Cell Cycle;Cell Death;Cell division;Cells;Chromosomal Instability;Chromosome abnormality;Chromosomes;comparative;Copy Number Polymorphism;Development;dimorphism;DNA Damage;Drosophila genus;Drug resistance;Early Diagnosis;Early treatment;Environmental Risk Factor;Epigenetic Process;Epithelium;Evolution;Female;Genes;Genetic;Genetic Epistasis;Genetic Variation;genome-wide analysis;Genomic Instability;Growth;Heterogeneity;Human;improved;in vivo;Link;Maintenance;male;Malignant Neoplasms;Mitosis;Modeling;Molecular Abnormality;neoplastic cell;notch protein;novel;Pattern;Play;Ploidies;Polyploid Cells;Polyploidy;Prognosis;programs;repaired;Reproducibility;Research;response;Role;sex;Sex Differences;sexual dimorphism;Specimen;Testing;tool;transcriptome sequencing;tumor;tumor growth;tumor heterogeneity;tumor progression;tumorigenesis;Variant;whole genome

PROJECT_TITLE: Polyploidy and Sex Dimorphism in a Drosophila Tumor Model

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]