NIH_SPENDING_CATS: Chronic Pain;Digestive Diseases;Interstitial Cystitis;Neurosciences;Pain Research;Urologic Diseases

ORG_CITY: NEW YORK

ORG_DEPT: DERMATOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition with a cardinal symptom of bladder related pain and it is common that bladder and colon pathological conditions co-occur with considerable overlap in symptom profiles across patient cohorts. While well-known clinically, there are no universally effective treatments available for bladder pain and bladder-colon cross sensitization due to a lack of understanding of the basic mechanisms. The current proposal aims to identify the cells and molecules involved in the pathogenesis of bladder pain and bladder-colon cross sensitization in the hopes of finding novel drug targets for treating both conditions.

PI_NAMEs: HU, HONGZHEN ;KIM, BRIAN  (contact)

PROGRAM_OFFICER_NAME: MULLINS, CHRISTOPHER V

PROJECT_TERMS: Abdominal Pain;Ablation;Afferent Neurons;Affinity;Applications Grants;Bladder;bladder pain;cathelicidin antimicrobial peptide;Cells;Chemicals;Chronic Disease;Clinical;cohort;Colon;Colonic Diseases;comorbidity;conditional knockout;Connective Tissue;Cyclophosphamide;designer receptors exclusively activated by designer drugs;Development;Diagnostic;Disease;effective therapy;Etiology;Frequencies;G-Protein-Coupled Receptors;Generations;Genetic;Habits;Human;humanized mouse;Hypersensitivity;IgE Receptors;Impairment;in vivo;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Interstitial Cystitis;Intestines;Intravesical Instillation;Irritable Bowel Syndrome;Irritants;Knockout Mice;Lead;Leukotriene C4;Ligands;Lower urinary tract;mast cell;Mechanical Stimulation;Mediating;Medical;Microglia;Modeling;Molecular;mouse model;Mucous Membrane;Mus;Neurogenic Bladder;Neurons;new therapeutic target;Nociceptors;novel therapeutic intervention;Organ;Overactive Bladder;Pain;Pathogenesis;Pathologic;Pathology;Patients;Pelvic Pain;Peptides;Peripheral;Peripheral Nervous System;Piezo 2 ion channel;Pilot Projects;psychiatric comorbidity;Quality of life;Recurrence;Role;selective expression;Spinal;Substance P;Symptoms;Syndrome;Testing;Therapeutic;Time;TRPV1 gene;Urination;Viral;Visceral;Visceral pain

PROJECT_TITLE: Molecular and cellular mechanisms of visceral pain and cross-organ sensitization

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: MEMPHIS

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: Project Narrative Mutation of genes involved in chromatin regulation frequently underlie cancer. We have identified a gene whose deletion causes cell death specifically in childhood cancers that are mutant for the SWI/SNF chromatin remodeler, in which the antagonistic Polycomb complex gains control. The proposed studies are designed to determine the normal function of this gene and how its deletion kills these childhood cancers, with the goal of improving our mechanistic understanding of the interplay between SWI/SNF and Polycomb complexes in cancer control.

PI_NAMEs: COCKFIELD, JORDAN A. (contact)

PROGRAM_OFFICER_NAME: ELJANNE, MARIAM

PROJECT_TERMS: academic program;Address;Adult;Affect;Award;base;beta catenin;Biology;Boston;Cancer cell line;Cancer Control;cancer genome;cancer predisposition;career;Cell Death;Cell Fate Control;cell growth;Cell Nucleus;Cell Survival;Childhood;Chromatin;Chromatin Remodeling Factor;Complement;Complex;CRISPR screen;CRISPR/Cas technology;Cytoplasm;Data;Dependence;design;Development;Diploidy;Equilibrium;expectation;experimental study;EZH2 gene;Frequencies;Gene Expression;gene function;Gene Mutation;gene repression;Genes;Genetic Predisposition to Disease;Genetic Transcription;Genome;genome sequencing;genome wide screen;genome-wide;Genomics;Goals;Hereditary Malignant Neoplasm;histone modification;Immunoprecipitation;improved;induced pluripotent stem cell;inhibitor;insight;knock-down;Laboratory Finding;Leadership;Link;Literature;Malignant - descriptor;Malignant Childhood Neoplasm;Malignant Neoplasms;Mammalian Cell;Mediating;member;Mentors;Modeling;Molecular;mutant;Mutate;Mutation;Nature;neoplastic cell;Normal Cell;notch protein;novel;novel therapeutics;Nuclear;Pathway interactions;Pediatric Neoplasm;pharmacologic;Polycomb;Positioning Attribute;post-doctoral training;Postdoctoral Fellow;PRC1 Protein;protein function;Proteins;Recurrence;Regulation;Repression;Repressor Proteins;Research;Residual state;Resources;Rhabdoid Cell;Rhabdoid Tumor;Ring Finger Domain;Role;Running;Saint Jude Children's Research Hospital;Signal Pathway;Signal Transduction;Signal Transduction Pathway;SMARCB1 gene;SWI/SNF Family Complex;Syndrome;Techniques;Testing;tool;Training;Transcriptional Activation;Transcriptional Regulation;Translating;Tumor Cell Line;ubiquitin-protein ligase;WNT Signaling Pathway;Writing

PROJECT_TITLE: What is the mechanism by which a gene essential for Rhabdoid tumor viability regulates Chromatin function?

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09A-R (20)]


ADMINISTERING_IC: HD

ED_INST_TYPE: GRADUATE SCHOOLS

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

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Caregiving Research;Clinical Research;Neurosciences;Pediatric

ORG_DEPT: PSYCHOLOGY

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

ORG_STATE: NY

PHR: PROJECT NARRATIVE Memories from early childhood do not persist into adulthood – a phenomenon that remains a neurobiological puzzle. This proposal aims to examine item-context memory and arousal in toddlers, and how it is modulated by caregivers, in order to advance understanding of the functions and plasticity of developing learning and memory systems in toddlers. In the long-term, this work has implications for why infant/toddler memories are so fragile and fleeting, yet at the same time, early caregiving experiences have enduring effects on cognition and socioemotional outcomes.

PI_NAMEs: YATES, TRISTAN SKYE (contact)

PROGRAM_OFFICER_NAME: MILLER, BRETT

PROJECT_TITLE: Caregiver influences on item-context memory and arousal in toddlers

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01B-M (20)]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Neurosciences

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE By retrieving past experiences from memory, humans and other animals can infer the value of choice options, including ones they have never encountered before. In this proposal, we aim to advance our understanding of how memory contributes to value-based choice by highlighting its role in shaping how and whether value is generalized across exemplars of a similar kind. Specifically, we suggest that the precision with which the past is remembered modulates our tendency to generalize, and propose to highlight the behavioral, neural, and computational signatures of this process by focusing on aging, which is known to affect memory precision.

PI_NAMEs: VAN GEEN, CAMILLA  (contact)

PROGRAM_OFFICER_NAME: SUTTERER, MATTHEW

PROJECT_TERMS: abstracting;Address;Affect;Age;age effect;age group;age related;age related changes;Aging;Animals;Apple;Back;base;Behavioral;Brain;Brain region;Categories;Chocolate;Cities;Data;Decision Making;Event;experience;Feedback;forgetting;Fruit;Functional Magnetic Resonance Imaging;functional MRI scan;healthy aging;Hippocampus;Human;indexing;Individual;Individual Differences;Learning;Link;Logic;Measures;Medial;member;Memory;Modeling;Neighborhoods;neural;Noise;novel;older adult;Oranges;Participant;Pattern;Performance;Persons;Predictive Value;Prefrontal Cortex;Process;Psychological reinforcement;Restaurants;Role;Semantics;Services;Shapes;Stimulus;targeted treatment;Testing;Therapeutic Intervention;Thinness;Time;Update;Variant;Visit;young adult

PROJECT_TITLE: Decision-making consequences of decreased memory precision with age


ADMINISTERING_IC: HL

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Brain Disorders;Cardiovascular;Cerebrovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Heart Disease;Prevention;Social Determinants of Health;Stroke

ORG_CITY: WASHINGTON

ORG_NAME: NATIONAL FORUM FOR HEART DISEASE AND STROKE PREVENTION, INC

ORG_STATE: DC

PHR: PROJECT NARRATIVE The National Forum for Heart Disease & Stroke Prevention (National Forum) 2024 Annual Meeting has the theme of “Advancing Health Equity Throughout America: Novel Data-Driven Approaches”. The meeting will raise awareness and fluency in the newly developed Vital Conditions for Health and Wellbeing framework among the anticipated 300 attendees including diverse medical and public health practitioners and researchers. It will also ensure that discussions on health equity and its implications for cardiovascular disease are framed within the Vital Conditions principles and present the importance of using data-driven approaches to achieve improvements in health policy and healthcare systems.

PI_NAMEs: CLYMER, JOHN M (contact)

PROGRAM_OFFICER_NAME: SHIROMA, ERIC JITSUO

PROJECT_TERMS: Accreditation;Address;Awareness;Back;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular health;Communities;community engagement;Consensus;Data;digital;Ensure;environmental change;Evaluation;follow-up;Funding;Future;Goals;Health;health care settings;health equity;Health Policy;Health Professional;Healthcare;Healthcare Systems;heart disease prevention;improved;Individual;Inequity;insight;Internet;Knowledge;Learning;Link;Maps;Medical;meetings;Modeling;National Heart, Lung, and Blood Institute;novel;Outcome;Participant;Perception;Performance;Personal Satisfaction;Persons;Policies;Policy Making;programs;Public Health;Recommendation;Research Personnel;resilience;social health determinants;Stroke prevention;Structure;symposium;Translating;Underrepresented Minority;Woman

PROJECT_TITLE: National Forum for Heart Disease & Stroke Prevention Annual Meeting 2024 - Advancing Health Equity Throughout America: Novel Data-Driven Approaches

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-O (M4)]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative Cell migration is ubiquitously important for development, homeostasis, and is altered in many diseases. Directed cell migration requires maintained polarization of key signaling pathways and cytoskeletal organization, however, the mechanisms by which cells maintain the flexibility to change direction is still not well understood. Completion of this proposal will determine how key signaling pathways and membrane-proximal F-actin regulation control cell speed and turning, while determining how signaling from these and other pathways are integrated to control faithful cell migration.

PI_NAMEs: PFANNENSTEIN, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: 3-Dimensional;Actins;Address;Animals;Area;Binding;Binding Proteins;Biological Process;Biosensor;Cell division;Cell membrane;Cell model;cell motility;Cells;Chemotaxis;Cues;Cytoskeletal Modeling;design;design and construction;Development;Disease;Dissection;Event;experimental study;F-Actin;Feedback;flexibility;Fluorescence;Generations;Goals;Growth;Homeostasis;Image;Immunologic Surveillance;Laboratories;Lateral;live cell imaging;Location;Mechanics;Membrane;migration;Migration Assay;Modeling;Morphogenesis;Motility;Organism;Pathway interactions;Pattern;PIK3CG gene;Play;polarized cell;prevent;Process;Protein Fragment;protein phosphatase inhibitor-2;Proteins;Psychological reinforcement;Quantitative Microscopy;recruit;Regulation;response;Role;Signal Pathway;Signal Transduction;Speed;Stimulus;System;Testing;Tissues;tool;trafficking;wound healing

PROJECT_TITLE: Investigating the role of signaling feedback in directed cell migration

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


ADMINISTERING_IC: OD

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: PROJECT NARRATIVE The Hydra, a small freshwater creature, has been pivotal in scientific discoveries, notably as the first animal in which regeneration was observed in 1744. While Hydra vulgaris is now a standard model in molecular research, the underutilized Hydra oligactis offers unique features for comparative studies. This proposal aims to bridge the gap by building resources and tools for H. oligactis, making it a comparable model to H. vulgaris, and therefore enabling new opportunities for research advancement in many scientific fields, including regeneration, aging, and neuroscience.

PI_NAMEs: JULIANO, CELINA  (contact)

PROGRAM_OFFICER_NAME: CONTRERAS, MIGUEL A

PROJECT_TERMS: adult stem cell;Aging;Animal Model;Animals;asexual;Atlases;Biophysics;Cell Lineage;Cells;Cessation of life;Chromosomes;Clustered Regularly Interspaced Short Palindromic Repeats;Cnidaria;Collaborations;Communities;comparative;Comparative Study;CRISPR/Cas technology;Data;Development;Developmental Biology;egg;Electroporation;Exhibits;foot;Fresh Water;Future;gene editing technology;gene function;Gene Transfer Techniques;Genes;Genome;genome sequencing;genome-wide;Genomics;Germ Cells;Goals;Hi-C;improved;knock-down;Knock-in;Laboratories;Mediating;Methodology;microbiome composition;microbiome research;Modeling;Modernization;Molecular;Natural regeneration;Nervous System;Neurosciences;Neurosciences Research;new technology;Nucleic Acid Regulatory Sequences;Play;Positioning Attribute;Production;Proteins;regenerative biology;repaired;Research;Resources;response;Role;Seminal;senescence;single-cell RNA sequencing;Small Interfering RNA;Standard Model;System;Temperature;Testing;tool;transcriptome sequencing;transcriptomics;Transgenic Organisms;United States National Institutes of Health;Variant

PROJECT_TITLE: Genetically enabling Hydra oligactis for comparative studies in development, regeneration and aging.

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Diabetes;Genetics;Human Genome

ORG_CITY: ANN ARBOR

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Understanding how insulin-producing pancreatic β cells fail is essential for generating better, more effective treatment options for patients suffering with diabetes. This application explores the contribution of mitochondrial (rather than nuclear) DNA deletions to diabetes by evaluating the consequences of mitochondrial DNA deletions on the β cell. Ultimately, data produced from this application will contribute to our understanding of the importance of mitochondrial health in maintaining β-cell function and blood glucose levels.

PI_NAMEs: DAVIDSON, REBECCA K (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Adult;Advisory Committees;Age;aging related disease;Animals;Applications Grants;Attenuated;Beta Cell;Bioenergetics;Bioinformatics;Blood Glucose;blood glucose regulation;career;Cell Physiology;Cell Survival;Cells;Clonal Expansion;Data;Development;Diabetes Mellitus;diabetic;Diabetic mouse;diabetogenic;Disease;DNA;DNA copy number;DNA Damage;Dominant-Negative Mutation;effective therapy;endocrine pancreas development;Epidemic;Etiology;exposed human population;Failure;Free Radicals;Functional disorder;functional loss;Generations;Genes;Genome;genome integrity;Genome Stability;Genomic Instability;Glucose;Glucose Intolerance;Goals;Health;helicase;Heritability;heteroplasmy;High-Throughput Nucleotide Sequencing;Human;Immunofluorescence Immunologic;Impairment;improved;in vivo;Inflammatory;insight;Insulin;Insulin Resistance;insulin secretion;Internal Medicine;islet;Islet Cell;Lead;Link;Maintenance;Mentors;Mentorship;Metabolic;Metabolic Diseases;Metabolic dysfunction;Michigan;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;mitochondrial DNA mutation;mitochondrial dysfunction;mitochondrial genome;Mitochondrial RNA;Molecular;mouse model;multidisciplinary;Mus;mutant;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;novel;Nuclear;Oxidation-Reduction;Oxidative Phosphorylation;Patients;Peripheral;Physiological;Positioning Attribute;Postdoctoral Fellow;postnatal;Predisposition;Prevalence;Productivity;programs;Proteins;Research;Respiration Disorders;response;Ribosomal RNA;Role;selective expression;Spirometry;Stains;stressor;Structure;Structure of beta Cell of islet;Technology;Testing;Training;Training Programs;Transfer RNA;Translations;Transmission Electron Microscopy;Transplantation;Universities;Writing;Xenograft Model

PROJECT_TITLE: The contribution of mitochondrial DNA damage to diabetes-related beta-cell failure

STUDY_SECTION: DDK

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


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Nutrition

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Heart failure, a common and debilitating disease, exhibits a metabolic signature of decreased succinyl CoA. The research in this proposal aims to understand the metabolic origins and physiological consequences of decreased succinyl CoA, as it is positioned at the intersection of three conditionally essential metabolic fates in the heart: forward tricarboxylic acid cycle flux, heme synthesis, and ketone oxidation. These studies will ultimately contribute to advancing efforts to expand therapeutic options for heart failure patients by examining fundamental heme biology and how the failing heart metabolically adapts during disease progression.

PI_NAMEs: POSS, ANNELISE  (contact)

PROGRAM_OFFICER_NAME: WANG, WAYNE C

PROJECT_TERMS: Ablation;Aerobic;Aminolevulinate;Aminolevulinic Acid;Basic Science;beta-Hydroxybutyrate;Biogenesis;Biology;Carbon;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;Cardiovascular Physiology;Cell Respiration;Cells;Chronic;Citric Acid Cycle;Coenzyme A-Transferases;cofactor;Computational Science;Core Facility;Data;Deterioration;Disease;Disease Progression;Down-Regulation;Electron Transport;Elements;Energy Metabolism;Energy-Generating Resources;Environment;Enzymes;Etiology;Exhibits;Failure;Fasting;flexibility;Functional disorder;Generations;Glucose;Goals;Heart;Heart failure;heart function;Heart Hypertrophy;heart metabolism;Heme;heme biosynthesis;Hepatic;Hepatocyte;Hour;Human;Hypertrophy;Keto Acids;Ketones;Knock-out;Knockout Mice;Knowledge;Label;Ligation;Lipids;Literature;loss of function;Maps;Metabolic;Metabolism;Mitochondria;Modeling;Molecular Profiling;mouse model;Mus;Muscle Cells;Muscle Fibers;Myocardial Degeneration;Myocardium;Myoglobin;novel;novel therapeutic intervention;Nutrient;Nutritional status;operation;oxidation;Oxidoreductase;Oxygen;Pathogenesis;Patients;Perfusion;Phase;Physiological;Porphyrins;Positioning Attribute;prevent;Process;Production;Proteins;Proteomics;Pump;Pyruvate;Regulation;Research;Research Personnel;response;skeletal;Skeletal Muscle;skills;Source;stable isotope;succinyl-coenzyme A;Supplementation;System;Technical Expertise;Testing;Therapeutic;tool;Tracer;Training;Work

PROJECT_TITLE: Mitochondrial succinyl CoA management at the intersection of heme and ketone metabolism

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F04A-V (20)]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Colorectal Cancer;Digestive Diseases;Precision Medicine

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative The optimization of medical imaging agents in cancer is a critical component for early diagnostics, complete surgical resection with minimal impact on surrounding tissues, and precision therapy. Optimizing design of imaging agents, including probes, requires understanding the physicochemical behavior of existing probes across the range of conserved spatial chemistries that are associated with cancerous tumor tissue. Here, I propose to combine my experience in computational data workflows and non-invasive label-free Fourier transform infrared (FT-IR) spectromicroscopy with new training in spatial omic technologies like CODEX to develop an integrative workflow for characterizing and identifying cancer-associated spatial chemistries to guide future cancer imaging probe development.

PI_NAMEs: HOLMAN, ELIZABETH A (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Address;Antibodies;Architecture;Behavior;Behavior assessment;Biopsy;Biopsy Specimen;Cancer Etiology;cancer imaging;Cancerous;Cells;Cessation of life;Chemicals;Chemistry;Clinical;Colon;colon cancer patients;Colonic Neoplasms;Colonoscopy;Colorectal Cancer;Computer software;computerized data processing;Curative Surgery;Data;Data Analyses;Data Set;design;Detection;Development;Diagnostic;diagnostic accuracy;Disease;Environment;Excision;experience;Fourier Analysis;Fourier Transform;Future;high dimensionality;Human;Image;imaging agent;imaging probe;Imaging Techniques;Immunofluorescence Immunologic;Immunohistochemistry;improved;in vivo imaging;indexing;innovation;inter-individual variation;interest;Intestinal Neoplasms;Knowledge;Label;Lead;Libraries;Literature;Malignant Neoplasms;Maps;Medical Imaging;Neighborhoods;Normal tissue morphology;Operative Surgical Procedures;Optics;Outcome;Pathologist;patient population;Patients;Performance;Plug-in;Positioning Attribute;Precision therapeutics;Preparation;Procedures;programs;Property;Protocols documentation;Publishing;Research;Resolution;Sampling;screening;Signal Transduction;single-cell RNA sequencing;software development;Source;structural biology;Structure;success;Synchrotrons;Technology;Testing;Therapeutic;Time;Tissue Sample;Tissue Therapy;Tissues;Tonsil;Training;treatment response;tumor;Tumor Tissue;United States;Validation;Variant

PROJECT_TITLE: Integrating highly multiplexed immunofluorescence with label-free 2D hyperspectral chemical imaging to interrogate the colorectal cancer tumor-invasive front

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10C-B (20)]


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

ORG_CITY: HOUSTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: PROJECT NARRATIVE Epigenetic dysregulation is a known driver of high-grade glioma (HGG) but pinpointing the precise epigenetic disturbances that accelerate tumor growth is still a challenge. We have found that Hp1bp3 is involved in chromatin remodeling, and patient sequencing data suggests that decreased expression is associated with enhanced susceptibility to glioma. Here I aim to evaluate the function of Hp1bp3 in HGG disease progression and its role in epigenetic dysregulation.

PI_NAMEs: LOZZI, BRITTNEY  (contact)

PROJECT_TERMS: Acceleration;Acetylation;Adult;ATAC-seq;Automobile Driving;Binding;Binding Proteins;Biological Assay;Carbon;cell growth;Cell Line;Cell Physiology;Characteristics;ChIP-seq;Chromatin;chromatin modification;chromatin remodeling;comparison control;Coupled;CRISPR/Cas technology;Data;Data Set;Diagnosis;Disease;Disease Progression;DNA Binding;DNA Binding Domain;Drug Targeting;Electroporation;Enhancers;enzyme pathway;Epigenetic Process;epigenetic regulation;epigenome;epigenomics;Event;Family;Folic Acid;gain of function;Gene Expression;gene network;Genetic;genome sequencing;genome-wide;genomic locus;Glioma;Goals;Growth;Heterochromatin;heterochromatin-specific nonhistone chromosomal protein HP-1;Histone Deacetylase;Histone Deacetylase Inhibitor;Histones;Human;human tissue;Immunohistochemistry;in utero;Investigation;Lead;loss of function;loss of function mutation;Malignant neoplasm of brain;Mass Spectrum Analysis;Metabolic;Metabolism;metabolomics;Methionine;Modeling;Molecular;mouse model;Mus;mutant;novel therapeutics;Oncogenic;Outcome;overexpression;Pathogenesis;patient derived xenograft model;Patients;Pattern;Predisposition;programs;Proliferating;Protein Dynamics;protein protein interaction;Proteins;Publishing;Regimen;Research;Role;self-renewal;standard of care;stem cells;System;Therapeutic;therapeutic development;Tissue Microarray;transcription factor;transcriptome sequencing;Transposase;tumor;tumor growth;tumor progression;Tumor Suppressor Proteins;tumorigenesis;Western Blotting;whole genome;Work

PROJECT_TITLE: Hp1bp3 oversees chromatin remodeling to slow tumor growth in high grade glioma

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


NIH_SPENDING_CATS: Genetics

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: Project Narrative Accurate chromosome segregation is essential to an organism’s growth and development. In eukaryotic cells, chromosome segregation is facilitated by the kinetochore, a conserved multiprotein complex that mediates the attachment of microtubules to chromosomes. This proposal seeks to identify and define the mechanisms of ubiquitin-mediated regulation of the kinetochore; these findings will illuminate principles governing a central biological process with implications for diseases marked by chromosome segregation errors.

PI_NAMEs: FRANK, ANDERSON ROSS (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TERMS: Address;Affinity Chromatography;Aneuploidy;Binding;Biochemistry;Biological Assay;Biological Models;Biological Process;Biology;cancer cell;Cell Cycle;Cell Physiology;Cells;Characteristics;chromosome number abnormality;chromosome replication;Chromosome Segregation;Chromosomes;Complex;Cullin Proteins;daughter cell;Disabling;Disease;Eukaryotic Cell;Event;Exhibits;experience;Family;Fellowship;Generations;Genetic;Genome;genome sequencing;Glycine;Goals;Growth;Growth and Development function;Human;Impairment;In Vitro;in vivo;insight;Kinetochores;Knowledge;Laboratory Finding;Life;Ligase;Malignant Neoplasms;Maps;Mass Spectrum Analysis;mechanical force;Mediating;member;method development;Microtubules;Mitotic spindle;Multiprotein Complexes;mutant;Mutation;Nature;novel;Organism;particle;Pathologic;Positioning Attribute;Post-Translational Protein Processing;Process;programs;protein complex;Proteins;Proteomics;Quality Control;Regulation;Reproduction;Research;Research Personnel;response;Role;Saccharomyces cerevisiae;Saccharomycetales;scaffold;segregation;Series;Sister Chromatid;Site;skills;synthetic lethal interaction;System;temperature sensitive mutant;Training;transcription factor;Ubiquitin;Ubiquitin family;ubiquitin ligase;Ubiquitin Like Proteins;ubiquitin-protein ligase;whole genome;Work;yeast genetics;Yeasts

PROJECT_TITLE: Ubiquitin-mediated regulation of kinetochore assembly and function

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-D (21)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Neurosciences;Pediatric

ORG_DEPT: BIOLOGY

PHR: Project Narrative Understanding the mechanisms linking caregiver odors with prosocial behavior is critical, as altricial animals rely on parental care to survive and children with developmental disorders such as fragile X syndrome and autism have altered olfactory perception. Our limited knowledge in this realm is mostly due to methodological hurdles in measuring neuronal activity in mammalian neonates, and a lack of relevant behaviors in neonate animal models, such as Xenopus tadpoles. This proposal seeks to fill the gap in our knowledge of neural mechanisms of social recognition in neonatal vertebrate brains by combining advanced neurophysiological techniques and a nontraditional model organism, poison frog tadpoles, which have in vivo imaging possibility and robust behavioral readouts.

PI_NAMEs: AKBARI, NAJVA  (contact)

PROJECT_TERMS: Address;Affect;affiliative behavior;Animal Model;Animals;autism spectrum disorder;Award;Behavior;Behavioral;Brain;brain circuitry;Brain imaging;Brain region;brain volume;Calcium;career;Caregivers;Caring;cell type;Child;Child Development;Communication;Complex;Computational Technique;conditioning;Cues;Data;Development;developmental disease;Disease;Dissection;dopaminergic neuron;Environment;Evaluation;experience;Exposure to;Female;Fostering;Foundations;Fragile X Syndrome;Gene Expression Profile;Genetic;Goals;Human;Immunohistochemistry;in vivo;in vivo imaging;in vivo two-photon imaging;Individual;Infant;Infant Behavior;Investments;Knowledge;Learning;Life;Life Experience;Link;locus ceruleus structure;Maps;Measures;Mentorship;Methodology;Midbrain structure;model organism;Modeling;Molecular;Mothers;multiphoton microscopy;Neonatal;neonatal brain;neonate;neural;neural circuit;neuromechanism;Neurons;neurophysiology;Neurosciences;Newborn Animals;Odors;olfactory bulb;Olfactory Pathways;Optics;Output;Personal Satisfaction;pharmacologic;Poison;Population;programs;Rana;Research;Resources;Role;Scientist;Sensory;single nucleus RNA-sequencing;skills;Smell Perception;social;social attachment;Social Behavior;Social Environment;Social Identification;Social Interaction;Tadpoles;Technical Expertise;Techniques;Testing;Time;tool;Training;two photon microscopy;Universities;Vertebrates;Visit;Work;Xenopus

PROJECT_TITLE: Tuning of infant olfactory circuits by early life interactions with caregivers

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02B-Y (20)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: OMAHA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: PROJECT NARRATIVE Staphylococcus aureus is the leading cause of bacteremia, infective endocarditis, and skin and soft tissue infections worldwide. Understanding the pathometabolism of S. aureus niche-specific infection is critical to develop new therapeutic strategies. This application proposes to assess the importance and effect of nitrogen metabolism during the establishment of S. aureus infection.

PI_NAMEs: BURKE, TAYLOR LAUREN (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Acids;Address;Aerobic;Affect;Amino Acids;Ammonium;Anabolism;Animals;Arginine;arginylglutamate;Bacillus subtilis;Bacteremia;Bacteria;bacterial genetics;bacterial metabolism;Biology;Blood;Carbon;career;Catabolism;Chemicals;Collaborations;Communicable Diseases;Complex;Data;Defect;Dependence;Disease;DNA Binding;Electrophoretic Mobility Shift Assay;Endocarditis;Ensure;Environment;Enzymes;experimental study;Faculty;Feedback;Fostering;Genes;Genetic;Genetic Transcription;Genus staphylococcus;Glucose;Glutamate-Ammonia Ligase;Glutamates;Glutamine;Gram-Positive Bacteria;Growth;Histidine;Human;Individual;Infection;Infectious Skin Diseases;Infective endocarditis;Ions;Knowledge;Label;Laboratories;Medical center;Medical Genetics;meetings;member;Mentors;Mentorship;Metabolic;Metabolism;metabolomics;meter;microbiome;mouse model;Mus;mutant;Nature;Nebraska;Nitrate Reductases;Nitrates;Nitrites;Nitrogen;Nitrogen Fixation;Nitrogen Fixation Genes;nitrogen metabolism;novel therapeutic intervention;Nucleotide Biosynthesis;Nutrient;Oligopeptides;pathogen;Pathogenesis;Pathway interactions;Peptide Transport;permease;Phenotype;Physicians;Physiological;Population;Process;Proline;promoter;Quantitative Reverse Transcriptase PCR;Reaction;Regulation;Reporting;Research;response;Role;Route;Scientist;Senior Scientist;Serine;Skin;Skin Tissue;soft tissue;Soft Tissue Infections;Source;Staphylococcus aureus;Staphylococcus aureus infection;Systems Biology;Tissue Model;Training;transcriptome sequencing;Universities;Urea;Virulence;vitamin biosynthesis

PROJECT_TITLE: Nitrogen Metabolism of Staphylococcus aureus

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07A-B (20)]


NIH_SPENDING_CATS: Bioengineering;Hematology;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: DALLAS

ORG_DEPT: PEDIATRICS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE Mechanical loading promotes the growth of bone forming cells that can regulate hematopoiesis. However, the mechanism through which this occurs is poorly understood. Here we investigate an ion channel that is sensitive to mechanical loading and could potentially mediate the way bone forming cells respond to mechanical cues to promote the formation of healthy bone and immune cells.

PI_NAMEs: SHIRAZI, JASMINE  (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Affect;bone;Bone Growth;bone imaging;Bone Marrow;Cations;Cells;Code;comparison control;Confocal Microscopy;cortical bone;Endothelial Cells;Exercise;Exhibits;Exons;Frequencies;Germ Lines;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Hindlimb Suspension;Immune;immune function;immune system function;improved;interstitial;Ion Channel;Knockout Mice;Laboratories;leptin receptor;Life;Location;Longevity;Lymphoid;Maintenance;mechanical force;mechanical load;mechanical signal;Mechanical Stimulation;Mechanics;Mediating;Mus;Osteogenesis;osteogenic;Outcome;Phenotype;Physiological;Piezo 1 ion channel;Population;Potassium Channel;premature;pressure;progenitor;Proliferating;Protein Truncation;reconstitution;Regulation;Reporter;response;shear stress;Signal Transduction;Signaling Protein;stem cells;Stretching;Stromal Cells;substantia spongiosa;Terminator Codon;Testing;Weight-Bearing state

PROJECT_TITLE: Mechanical regulation of hematopoiesis


PHR: Project Narrative Poor suppression of hepatic glucose production by insulin postprandially is a well-established feature of insulin resistance, which can lead to type 2 diabetes mellitus (T2DM). Unfortunately, development of therapeutics to control hepatic glucose production has been hampered by poor understanding of the direct mechanisms by which insulin controls liver glucose metabolism. This proposal aims to define the metabolic pathways and key regulatory steps involved in insulin’s acute control of liver glucose flux, and their dysregulation in insulin resistance, using stable isotope tracing, hyperinsulinemic clamps, and mouse genetics.

PI_NAMEs: STEFKOVICH, MEGAN LYNN (contact)

PROJECT_TERMS: 6-Phosphofructo-2-kinase;Acute;adenovirus mediated delivery;AKT inhibition;blood glucose regulation;Bolus Infusion;Canis familiaris;Cells;Closure by clamp;comparison control;constitutive expression;Data;Dependovirus;Dietary Intervention;Dimethyl Sulfoxide;Distal;Dominant-Negative Mutation;enzyme activity;Equilibrium;euglycemia;experimental study;Failure;Fasting;feeding;Fructose;Fructose-1,6-Bisphosphatase;Gene Expression;Generations;Genes;Genetic Transcription;Gluconeogenesis;Glucose;glucose metabolism;glucose output;glucose production;glucose uptake;Glutamine;Glycerol;Glycogen;glycogen metabolism;Glycogen Phosphorylase;glycogenolysis;Glycolysis;Goals;Hepatic;Hepatocyte;High Fat Diet;Hyperglycemia;Hyperinsulinism;Impairment;in vivo;inhibitor;Insulin;Insulin Resistance;insulin sensitivity;insulin signaling;Isoenzymes;Knock-out;Label;Lipids;Liver;Measures;Mediating;Mediator;Messenger RNA;Metabolic Diseases;Metabolic Pathway;Methods;mouse genetics;Mus;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;Obese Mice;obesogenic;overexpression;Pathway interactions;pharmacologic;Phosphorylation;Phosphotransferases;prevent;Process;protein expression;Protein-Serine-Threonine Kinases;Proto-Oncogene Proteins c-akt;Regulation;Role;Serine;Signal Transduction;Site;stable isotope;Testing;therapeutic development;Time;Transcriptional Regulation;uptake

PROJECT_TITLE: Insulin's acute regulation of hepatic glucose utilization


NIH_SPENDING_CATS: Cardiovascular;Diabetes;Genetics;Heart Disease;Human Genome;Nutrition;Obesity;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: PROJECT NARRATIVE Novel gut hormone-based agonists demonstrate great potential for improving metabolic health and reducing cardiovascular events in diabetes and obesity, but the mechanisms are not fully elucidated. Research aimed at understanding the impact of these novel drugs on the cardiovascular system may lead to the development of more targeted cardiovascular therapeutics.

PI_NAMEs: JUGUILON, CODY  (contact)

PROGRAM_OFFICER_NAME: LIDMAN, KARIN FREDRIKSSON

PROJECT_TERMS: Adult;Agonist;Aorta;Area;Arr2;ATAC-seq;Body mass index;Body Weight;Body Weight decreased;Calcium;Calcium Signaling;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;cardiovascular health;cardiovascular risk factor;Cardiovascular system;career development;Cause of Death;Cell Line;Cell Nucleus;cell type;Cells;Central Nervous System;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Communication;Computing Methodologies;Coronary;CRISPR/Cas technology;Cyclic AMP;Development;Diabetes Mellitus;Diastolic blood pressure;diet-induced obesity;Echocardiography;Education;Endothelial Cells;Environment;Epidermal Growth Factor Receptor;epigenomics;Event;Fellowship;Future;Gastric Emptying;gastric inhibitory polypeptide receptor;Gene Expression;Genetic;GLP-I receptor;Glucagon Receptor;glucagon-like peptide 1;Glucose;Glycosylated hemoglobin A;Health;Heart;heart function;hormonal signals;Hormones;human induced pluripotent stem cells;improved;In Vitro;in vivo;in vivo Model;Individual;induced pluripotent stem cell;induced pluripotent stem cell technology;innovation;insight;insulin secretion;Knowledge;Left;loss of function;Maps;Metabolic;Metabolic stress;Metabolism;Migration Assay;modifiable risk;Molecular;multi-electrode arrays;multiple omics;Mus;Myography;Nitric Oxide;notch protein;novel;novel therapeutics;Nuclear RNA;Obese Mice;Obesity;Pancreas;Patients;Pharmaceutical Preparations;Phenotype;Prevalence;Production;receptor;Research;Research Personnel;response;Risk Factors;Satiation;Scientist;Signal Pathway;Signal Transduction;single nucleus RNA-sequencing;Small Nuclear RNA;Technical Expertise;Therapeutic;Tissues;Training;trait;Transcript;transcriptome sequencing;transcriptomic profiling;transcriptomics;Transforming Growth Factor beta;Translational Research;Tube;Universities;Variant;Vascular Cell Adhesion Molecule-1;Vascular Endothelial Growth Factors;Vasodilation;whole genome;XCL1 gene

PROJECT_TITLE: Causal Mechanisms of Novel Gut-Hormone Agonists on Cardiovascular Health


NIH_SPENDING_CATS: Genetics;Immunotherapy

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

PHR: Project Narrative The cGAS/STING pathway and regulatory T cells (Tregs) share essential but opposing roles in many inflammatory immune responses – which often coincide with elevated temperatures (e.g. fever-range temperature, FRT) – yet the mechanisms intertwining FRT and STING activation in Tregs remain unknown. This proposal aims to establish the individual and combined effects of FRT and STING activation on Treg function and metabolism. We hypothesize that cGAS/STING pathway activation glycolytically reprograms Tregs into inflammatory T cells and that this is potentiated at FRT during inflammatory immune responses.

PI_NAMEs: SMITH, RACHAEL CORYNNE (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: 5'-AMP-activated protein kinase;Affect;Agonist;Anti-Inflammatory Agents;anti-tumor immune response;Autoimmune;Automobile Driving;CD4 Positive T Lymphocytes;Cell Death;Cell Nucleus;Cell Physiology;Cell Respiration;Cells;Cellular Metabolic Process;Cellular Stress;CTLA4 gene;Cyclic GMP;cytokine;Data;DNA;ds-DNA;effector T cell;Ensure;Environment;Epigenetic Process;Exhibits;experimental study;Exposure to;extracellular;Extravasation;Fever;FOXP3 gene;FRAP1 gene;Gene Activation;Gene Expression;Gene Expression Profile;gene interaction;Glycolysis;Goals;Hyperthermia;IL2RA gene;Immune;Immune response;Immunotherapy;improved;In Vitro;in vivo;Individual;Infection;Inflammation;Inflammation Mediators;Inflammatory;inhibitor;Interferon alpha;Interferon Type I;Interferons;Investigation;Mediating;Mediator;Mentors;Metabolic;Metabolic stress;Metabolism;Methods;Mitochondria;multidisciplinary;Natural Immunity;neoplastic cell;novel;novel strategies;Nucleic Acids;Oxidative Phosphorylation;Pathway interactions;Patients;Phenotype;Physiological;prevent;Production;programs;Regulatory T-Lymphocyte;Reporting;Research;response;RNA;Role;Scientist;sensor;Solid Neoplasm;Stimulator of Interferon Genes;success;synergism;T cell differentiation;T cell response;T-Cell Activation;T-Lymphocyte;T-Lymphocyte Subsets;Temperature;Testing;Tissues;Training;transcription factor;tumor;Tumor Immunity;Tumor Tissue;vaccine response;Vaccines;Viral

PROJECT_TITLE: The Impact of STING Activation and Fever on Regulatory T cell Function and Stability

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07B-G (20)]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Orphan Drug;Pancreatic Cancer;Prevention;Rare Diseases

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Pancreatic cancer is one of the deadliest human cancers, in part because diagnosis most frequently occurs at advanced stages when therapies are largely ineffective. Early stages of pancreatic cancer progression are not well understood, and better understanding of pancreatic cancer initiation and development could lead to earlier detection, new therapies, and better patient outcomes. The work proposed here will utilize acinar explants and novel mouse models to define the role of the ATF4 transcription factor in early stages of pancreatic cancer, including in acinar-ductal metaplasia and in the formation of PanIN lesions.

PI_NAMEs: ZIOLKOWSKI, LEAH MARIE (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Acceleration;Acinar Cell;Address;Affect;American;Binding;Biological Assay;biomarker identification;Bromodeoxyuridine;Cancer Biology;Cancer Etiology;cancer initiation;CDKN1A gene;Cell Aging;Cells;Cellular Stress;Cessation of life;chemotherapy;chromatin immunoprecipitation;cytokine;Data;Death Rate;derepression;Development;Diagnosis;Disease;DNA Sequence Alteration;Down-Regulation;Duct (organ) structure;early detection biomarkers;Early Diagnosis;Early treatment;Electron Microscopy;Exocrine pancreas;Failure;Genes;Genetic Transcription;Goals;Human;human disease;Immunofluorescence Immunologic;Immunoprecipitation;improved;in vivo;Inflammatory;Inhibition of Matrix Metalloproteinases Pathway;KPC model;KRAS oncogenesis;KRASG12D;Lesion;Ligation;Link;Lipids;Malignant neoplasm of pancreas;Malignant Neoplasms;Matrilysin;Measures;Mediating;Metaplasia;Mitochondria;mitochondrial dysfunction;mouse model;Mus;Mutation;Natural regeneration;new therapeutic target;novel;novel therapeutics;Oxidative Stress;Pancreas;pancreas development;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;Pancreatic enzyme;Pancreatic Intraepithelial Neoplasia;pancreatic neoplasm;pancreatic tumorigenesis;Pancreatitis;Pathology;Pathway interactions;Patient-Focused Outcomes;Patients;Play;premalignant;prevent;Process;promoter;protein expression;Regenerative response;Regulation;Repression;Research;Resectable;response;RNA;Role;Sampling;senescence;Stains;Stress;Survival Rate;Symptoms;Testing;Therapeutic;Time;Tissues;TP53 gene;transcription factor;Transcription Factor AP-1;transcriptome sequencing;tumor;tumor progression;tumorigenesis;tumorigenic;Unresectable;Up-Regulation;Work

PROJECT_TITLE: Defining novel functions of ATF4 in early stages of pancreatic cancer tumorigenesis


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative Portions of human cerebral cortex are greatly expanded relative to non-human primates and while this expansion likely underpins the unique capabilities that humans possess, it may also enable neuropsychiatric diseases, such as Alzheimer's dementia and schizophrenia, that have only limited analogs in non-human species. We propose to accurately map evolutionary expansion with state-of-the-art interspecies registration and identify the gene expression and cell types that drive these patterns. This research will improve the translatability of studies using non-human primate models, enrich our understanding of how the complex behaviors that make us human arose, and provide insight into predominately human mental and neurological disorders.

PI_NAMEs: ROSEN, BURKE QUARTMAN (contact)

PROGRAM_OFFICER_NAME: VAN'T VEER, ASHLEE VICTORIA

PROJECT_TERMS: Acceleration;Address;Algorithms;Alzheimer's Disease;analog;Anatomy;Area;Atlases;Attention;Behavior;Brain;brain based;Brain Diseases;BRAIN initiative;Brain Mapping;cell type;Cells;Cerebral cortex;Cognitive;cognitive capacity;Collaborations;Complex;computational neuroscience;Data;Data Set;density;empowerment;Evolution;Functional Magnetic Resonance Imaging;Future;Gene Expression;Gene Expression Profile;Genes;Genetic;Genetic Transcription;Hominidae;Human;improved;insight;Investigation;Language;Macaca;Maps;Measures;Mental disorders;Methodology;Modeling;multidisciplinary;multimodal neuroimaging;multimodality;Myelin;Nervous System Disorder;Neuroanatomy;neuroimaging;neuropsychiatric disorder;neuropsychiatry;nonhuman primate;Pan Genus;Pathology;Pattern;Play;Positioning Attribute;Primates;Proliferating;Reporting;Research;Research Personnel;Resolution;Rest;Role;Schizophrenia;social;Surface;Taxonomy;Technology;Testing;Training;transcriptomics;translational potential

PROJECT_TITLE: Evolutionary expansion of human cerebral cortex: spatial patterns and transcriptional correlates


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Neurosciences;Pediatric;Prevention;Substance Misuse;Underage Drinking

ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

PHR: PROJECT NARRATIVE Impulsivity is a strong risk factor for early initiation of alcohol use, however the ways in which different facets of impulsivity interact with other individual and environmental factors to increase risk for alcohol use is not well understood. The Acquired Preparedness Model (APM) provides a framework for understanding how reward- related impulsivity influences the relationship between alcohol-related learning experiences and expectancies about the effects of alcohol prior to the initiation of alcohol use. The proposed project aims to test this proposed developmental pathway in a sample of over 11,000 9–10-year-olds from the Adolescent Brain Cognitive Development (ABCD) study using questionnaire, behavioral, and neural measures of reward-related impulsivity.

PI_NAMEs: PORTER, ANNA  (contact)

PROGRAM_OFFICER_NAME: ZHA, WENXING

PROJECT_TERMS: 10 year old;Acute;addiction;Address;Adolescence;Adolescent;Age;Alcohol abuse;Alcohol consumption;alcohol effect;alcohol expectancy;alcohol exposure;alcohol risk;alcohol use disorder;alcohol use initiation;Alcohols;behavior measurement;Behavioral;biopsychosocial;Brain;career;cognitive control;cognitive development;Corpus striatum structure;critical developmental period;Data;Data Analyses;Data Set;Development;Developmental Process;disorder risk;early adolescence;early alcohol use;Educational workshop;Environment;Environmental Risk Factor;Equation;Expectancy;experience;Factor Analysis;financial incentive;Funding;Goals;Grant;Heterogeneity;Impulsivity;Individual;Intervention;Investigation;Learning;Measures;meetings;Mentors;Methods;Missouri;Modeling;National Institute on Alcohol Abuse and Alcoholism;neural;Neurobiology;neuroimaging;Neurosciences;novel;Participant;Pathway interactions;Patient Self-Report;Pattern;person centered;population based;Prefrontal Cortex;Prevention;Prevention strategy;Process;psychologic;Psychopathology;Questionnaires;Readiness;Reporting;Research;Rewards;Risk;Risk Factors;Role;Running;Sample Size;Sampling;Science;Scientist;Series;Site;Statistical Methods;statistics;Structure;Subgroup;substance use;symposium;System;Testing;Theoretical model;Training;Training Programs;trait;underage drinking;Universities;Work;Writing;Youth

PROJECT_TITLE: A Multi-Method Investigation of the Role of Reward-Related Impulsivity in the Development of Alcohol Expectancies in Early Adolescence

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Cancer Genomics;Clinical Research;Genetics;Health Services;Human Genome;Lung;Lung Cancer;Machine Learning and Artificial Intelligence;Prevention;Tobacco;Tobacco Smoke and Health

ORG_CITY: Chicago

ORG_NAME: NORTHWESTERN UNIVERSITY

PHR: No existing technique allows accurate and cost-effective screening for early stages of lung cancer. This project will finalize the development of a new lung cancer screening test based on the optical analysis of the chromatin structure of cells brushed from the cheek mucosa that would enable highly accurate identification of patients with lung cancer, including stage I, among the general population, and can be performed at home, or in convenient care or primary care settings.

PI_NAMEs: BACKMAN, VADIM  (contact);BHARAT, ANKIT ;SUBRAMANIAN, HARIHARAN

PROGRAM_OFFICER_NAME: DIVI, RAO L

PROJECT_TERMS: Adenocarcinoma;Age;Air Pollution;Algorithms;Architecture;Artificial Intelligence enhanced;Biological Markers;Body mass index;Brush Cell;Cancer Detection;Cancerous;candidate marker;carcinogenesis;Caring;Cells;Cessation of life;Cheek structure;chemoradiation;Chromatin;Chromatin Structure;Clinical;clinical practice;Clinical Research;clinical translation;Clinical Trials;cohort;conformational alteration;cost;cost effective;Data;Data Set;deep learning;Demographic Factors;demographics;Detection;Development;Diagnosis;Diagnostic;diagnostic technologies;Disease;Distant;DNA;Drops;Early Diagnosis;early screening;Electron Microscopy;electron tomography;Electrons;Eligibility Determination;Ensure;Epigenetic Process;Etiology;Euchromatin;Evaluation;Exposure to;Female;follow-up;Fostering;Funding;Future;Gases;Gender;General Population;Genetic Transcription;Genome Mappings;Genomics;Goals;Heterochromatin;Histologic;Histology;Histones;Home;Image;Immunotherapy;industry partner;interest;Label;Length;Lesion;Link;liquid biopsy;Lung;lung cancer screening;lung carcinogenesis;male;Malignant neoplasm of lung;Malignant Neoplasms;Measurable;Measurement;Measures;Methods;Microscopy;minimally invasive;Molecular;Molecular Conformation;mortality;Mucous Membrane;nanocytology;nanoimaging;nanoscale;Nanoscopy;nanosensors;neoplastic;non-compliance;non-smoker;non-smoking;novel strategies;Operative Surgical Procedures;Optics;Oral mucous membrane structure;Patients;Pattern;Performance;Phenotype;Play;Population;Predictive Value;premalignant;Premalignant Cell;preservation;primary care setting;prospective;Race;Radon;Recommendation;Regulation;Risk;Risk Factors;Robotics;Role;Scanning;screening;screening guidelines;Self Administration;sensor technology;Series;simulation;single molecule;Smoker;Smoking History;Source;Specificity;spectroscopic imaging;Stage at Diagnosis;Swab;Techniques;Technology;technology development;Testing;theories;Three-dimensional analysis;Time;Tobacco;Trachea;transcriptomics;Translating;transmission process;tumor;uptake;Validation;X-Ray Computed Tomography

PROJECT_TITLE: Translating buccal nanocytology for lung cancer screening into clinical practice

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CTH-E (57)]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Diabetes;Infectious Diseases;Maternal Health;Microbiome;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Urologic Diseases;Women's Health Research

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: PROJECT NARRATIVE Type 2 diabetes is one of the most common diseases in the world, and type 2 diabetics face double the risk of microbial infections, along with increased complications and death due to infections. The vaginal microbiome is a known factor in susceptibility to genital and urinary tract infection and a source of pathogen translocation to vulnerable body sites, but it has never been studied in the context of type 2 diabetes. This project will investigate the type 2 diabetic vaginal microenvironment, including the microbiome, and determine the impact on infection by a pathogen that disproportionately infects diabetics, with the goal of identifying components of the diabetic vaginal environment that confer protection or susceptibility to infection to develop prophylactic and therapeutic treatments.

PI_NAMEs: ROBERTSON, CLARE MARIE (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: 16S ribosomal RNA sequencing;Aerobic;Aerococcus;Animal Model;Antibiotics;Antimicrobial Resistance;Bacteria;Bacterial Adhesion;Bacterial Infections;Biological Models;Bioreactors;Cessation of life;Characteristics;Chronic;Clinical;clinically relevant;cohort;college;Colony-forming units;Communities;cytokine;Diabetes Mellitus;diabetic;Disease;Dissociation;Distant;dysbiosis;Electrical Resistance;Enrollment;Environment;Enzyme-Linked Immunosorbent Assay;Epithelium;experience;Face;fitness;General Population;Genetic;Genetic Transcription;Genitourinary system;Genitourinary System Infection;genome sequencing;Gestational Diabetes;Goals;Group B Streptococcus colonization;Growth;gut bacteria;gut microbiome;Homeostasis;Hospitalization;Hospitals;host-microbe interactions;Human;Human Microbiome;Immune;Immune response;Immunity;Infection;infection burden;infection risk;Inflammation;Inflammatory;innovation;Lactobacillus;Length;Mediating;Mediation;Medicine;Membrane;Mentorship;Metabolic;Metabolic Diseases;Metabolism;metabolome;metabolomics;Microbe;microbial;microbial community;microbiome;microbiome alteration;microbiota;Modeling;Morbidity - disease rate;mortality;mosaic;Mucous Membrane;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;Nutrient;opportunistic pathogen;Organoids;pathogen;Pathogenesis;Patients;Persons;Phenotype;Population;Predisposition;Pregnancy;Pregnant Women;prevent;Prevotella;prophylactic;Proteins;recruit;reproductive tract;Research;response;Risk;Role;Sampling;Severities;Site;Skin;Source;stem cell organoids;Streptococcal Infections;Streptococcus Group B;Swab;Symptoms;systemic inflammatory response;targeted treatment;Testing;Therapeutic;Tight Junctions;tool;Training;transcriptomics;Type 2 diabetic;Urinary tract;Urinary tract infection;urogenital tract;Vagina;vaginal microbiome;vaginal microbiota;vaginal mucosa;Vaginitis;Visit;whole genome;Woman;Work

PROJECT_TITLE: Investigating Type 2 Diabetic Vaginal Microbiota and Susceptibility to a Urogenital Pathogen

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


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Lung;Orphan Drug;Rare Diseases

ORG_CITY: MISSOULA

ORG_NAME: UNIVERSITY OF MONTANA

ORG_STATE: MT

PHR: Project Narrative Exposure to crystalline silica particles results in chronic inflammation in a variety of tissues and disease models. Lysosome membrane permeabilization is a common event in multiple models of particle-induced inflammation including crystalline silica yet the mechanisms driving these diseases remain undefined. The proposed research will address this gap in knowledge by describing the mechanisms of crystalline silica-induced lysosome membrane permeabilization and downstream inflammation in isolated macrophage lysosomes.

PI_NAMEs: ALBRIGHT, JACOB  (contact)

PROJECT_TERMS: Accounting;acid sphingomyelinase;Acute;Alveolar Macrophages;amphiphilicity;Apoptotic;Asbestos;Automobile Driving;bafilomycin A1;Biological;Biophysics;Cathepsins B;Cell Death;Cell Membrane Permeability;Cell Physiology;Cell Proliferation;Ceramides;Cessation of life;Cholesterol;Chronic;Chronic Disease;chronic inflammatory disease;combat;Confocal Microscopy;cytokine;Cytosol;design;Disease;disease model;Economic Burden;Environment;Enzymes;Event;Exposure to;Failure;Fiber;Fluorescence Anisotropy;galactosylgalactosylglucosylceramidase;Galectin 3;Goals;Health Care Costs;Imipramine;Inflammasome;Inflammation;Inflammatory;inflammatory lung disease;inhibitor;Interleukin-1 beta;Knowledge;lipid metabolism;lipidomics;Lipids;Lung Diseases;lysosome membrane;Lysosomes;Macrophage;Macrophage Activation;Mass Spectrum Analysis;Measurement;Measures;Mediating;Mediator;Medical;Membrane;membrane model;Metabolism;metal oxide;Methods;Modeling;Molecular;mortality;Multiprotein Complexes;Mus;nanoparticle;new therapeutic target;novel;novel therapeutic intervention;Occupational;Outcome;particle;Pathologic;Pathologic Processes;Pathway interactions;Permeability;Pharmaceutical Preparations;Play;prevent;Protocols documentation;Pulmonary Fibrosis;Reporting;Research;Resistance;Role;Senile Plaques;Series;Silicon Dioxide;Silicosis;small molecule inhibitor;Sphingolipids;Sphingomyelins;Sphingosine;sphingosine 1-phosphate;sphingosine kinase;Techniques;Testing;therapeutically effective;time use;tissue injury;Tissue Model;Toxic effect;Urate;vacuolar H+-ATPase;Work

PROJECT_TITLE: Sphingomyelin Metabolism Impacts on Crystalline Silica-Induced Outcomes


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: Project Narrative: The cause of memory loss in Alzheimer’s disease remains largely unknown. It is essential to understand the molecular mechanisms underlying hippocampus-dependent learning and memory, the earliest and most affected by the disease. This project will determine the role of the Late onset Alzheimer’s disease – linked PICALM in adult hippocampal neurogenesis and establish PICALM as a novel contributor to hippocampus-dependent memory impairments in Alzheimer’s disease.

PI_NAMEs: APONTE-COFRESI, LUIS ALBERTO (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: abeta accumulation;Adaptor Signaling Protein;Address;Adult;Affect;Age;Aging;Alzheimer's Disease;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Amyloidosis;Binding;Brain;brain parenchyma;Case Study;Cells;Cerebrovascular system;Clathrin;Clathrin Adaptors;Clinical;Cognitive;Cognitive deficits;conditional knockout;Cytoplasmic Granules;Dementia;dentate gyrus;Development;Discrimination;Disease;Disease Progression;embryonic stem cell;Endocytosis;Episodic memory;experimental study;Genes;Genetic;Genetic Polymorphism;genetic risk factor;genome wide association study;Hippocampus;Human;hyperphosphorylated tau;Impairment;induced pluripotent stem cell;Induced pluripotent stem cell derived human neuron;insight;knock-down;Knock-out;Late Onset Alzheimer Disease;Learning;Length;Link;Mediating;Memory;Memory impairment;Memory Loss;Metabolism;mild cognitive impairment;Molecular;Morphology;mouse model;Mus;nerve stem cell;neural;Neurofibrillary Tangles;neurofilament;neurogenesis;Neuronal Differentiation;Neurons;novel;novel therapeutics;Pathologic;Pathology;patient derived induced pluripotent stem cells;Patients;Pattern;Phosphatidylinositols;Play;Process;Proliferating;Prosencephalon;protein B;protein metabolism;recruit;Reporting;Risk Factors;Role;self-renewal;stem;stem cells;Tubulin

PROJECT_TITLE: The Role of PICALM in Regulating Neurogenesis in Alzheimer's Disease


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Mental Health;Mental Illness;Prevention;Serious Mental Illness;Sleep Research;Suicide;Suicide Prevention;Women's Health Research

ORG_DEPT: PSYCHIATRY

PHR: PROJECT NARRATIVE Suicide is a leading cause of death among reproductive-aged females, yet we lack an understanding of the day- to-day factors underlying acute changes in depression and suicidality. The primary mentor’s RCTs (perimenstrual E2+P4 vs. PBO) highlight that cyclical steroid withdrawal around menses triggers worsened suicidality and depression that is reversible with short-term hormone supplementation. Recognizing the infeasibility of long-term hormone supplementation and identifying sleep as a potential physiological mediator and treatment target, the proposed study, involving 150 AFAB transdiagnostic patients, aims to explore the role of sleep in perimenstrual exacerbation of suicidality/depression, employing high temporal resolution sleep data from wearables and experimental ovarian hormone manipulation to establish causality.

PI_NAMEs: NAGPAL, ANISHA  (contact)

PROGRAM_OFFICER_NAME: AVENILLA, FRANK R

PROJECT_TERMS: Acute;aged;analytical method;archived data;Area;Biological;cancer risk;career;Cause of Death;Clinical;Clinical Trials;Coagulation Process;Cognition;Data;Depressed mood;Diagnostic;digital health;Estradiol;Etiology;Event;experience;experimental study;Feeling suicidal;Female;Funding;Goals;high risk;Hormonal;hormone sensitivity;Hormones;Hospitalization;Individual Differences;insight;Intervention;Laboratories;life span;Link;Longitudinal Studies;Mediating;Mediation;Mediator;Medicine;Menstrual cycle;Menstruation;Mental Depression;Mental disorders;Mentors;Mentorship;Methods;Modeling;multilevel analysis;National Institute of Mental Health;novel;Outcome;Ovarian;Ovarian hormone;Pathway interactions;Patient Recruitments;Patient Self-Report;patient subsets;Patients;perimenstrual;personalized medicine;Persons;Phase;Physiological;Placebos;Prevention;Process;Progesterone;Psychiatry;Randomized, Controlled Trials;Recurrence;reducing suicide;reproductive;Research;Research Priority;Resolution;Risk;Role;Sampling;Sleep;Sleep disturbances;sleep health;sleep pattern;Statistical Models;Steroids;Strategic Planning;suicidal;suicidal behavior;suicidal risk;Suicide;Suicide attempt;Suicide prevention;Supplementation;Surveys;temporal measurement;Testing;Time;Training;United States;United States National Institutes of Health;wearable data;wearable device;Withdrawal;Work

PROJECT_TITLE: Sleep as a Mechanism of Premenstrual Exacerbation of Depression and Suicidality

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F16-T (21)]


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

PHR: PROJECT NARRATIVE The cornerstone of medical therapy in HF is guideline-directed medical therapy (GDMT), including beta- blockers and renin-angiotensin-aldosterone antagonists, which address HF by decreasing energy demand, but do not address energy supply, creating a need for novel therapeutics for HF. Cardiac tissue in patients with HF exhibit mitochondrial structural and bioenergetic abnormalities, and mitochondria-rich extracellular vesicles (M- EVs) from induced pluripotent stem cells (iPSCs) have emerged as a promising method to restore myocardial bioenergetics and function. As there is potential synergistic valve in combined therapy, I propose a study evaluating M-EV therapy in addition to select GDMT in HF.

PI_NAMEs: LI, JIWEN  (contact)

PROJECT_TERMS: Address;Adrenergic beta-Antagonists;Aldosterone;Aldosterone Antagonists;Angiotensin Receptor;Angiotensins;antagonist;Anterior;Apoptosis;Arteries;Attenuated;Bioenergetics;Biogenesis;Biological;Biological Assay;Candidate Disease Gene;Cardiac;cardiac magnetic resonance imaging;Cardiac Myocytes;Cardiomyopathies;carvedilol;Cicatrix;Cluster Analysis;Combined Modality Therapy;Congestive Heart Failure;Control Groups;Data;Databases;Development;Diagnosis;differential expression;Dilated Cardiomyopathy;Energy consumption;Energy Supply;Energy-Generating Resources;Exhibits;Experimental Designs;extracellular vesicles;Female;functional restoration;Future;Genes;Guidelines;Health;Heart;Heart failure;high throughput analysis;Hospitalization;Hypertrophic Cardiomyopathy;Hypoxia;Impairment;improved;In Vitro;in vivo;induced pluripotent stem cell;induced pluripotent stem cell derived cardiomyocytes;Infarction;Injections;injured;Injury;innovation;insight;ischemic cardiomyopathy;Left;Ligation;Losartan;male;Medical;Metabolic;metabolomics;Methods;Mitochondria;Mitochondrial DNA;Modeling;Morbidity - disease rate;mortality;mouse model;multiple omics;Mus;Myocardial;myocardial injury;Myocardium;novel;novel strategies;novel therapeutics;Ontology;Outcome;Pathology;Pathway Analysis;Pathway interactions;Patients;pharmacologic;Ploidies;Production;protective effect;protein protein interaction;Proteome;Proteomics;Regimen;Renin;repaired;Respiratory physiology;restoration;stem cells;Structural defect;Supplementation;Technology;Testing;Therapeutic;Tissues;transcriptome sequencing;transcriptomics;Translations;Treatment Failure;Visualization;Work;Workload

PROJECT_TITLE: Mitochondrial therapy in conjunction with guideline directed medical therapy in cardiomyopathy

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


PHR: PROJECT NARRATIVE The objectives of this project are to characterize how the antitoxin DarG1 from the DarTG1 toxin- antitoxin (TA) system both: (1) senses lytic bacteriophage (phage) DNA metabolism in infected E. coli and (2) senses altered DNA metabolism in uninfected E. coli. Specifically, I will identify the viral DNA replication processes necessary for DarG1 to sense infection and the DNA metabolism perturbations—changes to DNA replication or repair—sufficient for DarG1 to free DarT1 (i.e., to “sense” a non-existent infection) in uninfected E. coli. Determining how DarG1 monitors ssDNA- related processes to catch phage-induced alterations could be a model of anti-viral immune sensing, as DarG1-like NADAR proteins are found across prokaryotes & eukaryotes, so any identified DarG1 surveillance mechanism could be echoed in other anti-viral systems.

PI_NAMEs: GIBBS, KYLE DANE (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Adjuvant;ADP ribosylation;anti-toxin;antiviral immunity;Bacteria;Bacteriophage T4;Bacteriophages;Capsid;Cells;ChIP-seq;Data;DNA;DNA biosynthesis;DNA Damage;DNA lesion;DNA metabolism;DNA Repair;DNA replication fork;DNA Replication Inhibition;DNA Sequence Alteration;DNA-Binding Proteins;ds-DNA;Escherichia coli;Eukaryota;Fluorescence Microscopy;Genetic;Genetic Recombination;Genetic Transcription;Genome;Glycoside Hydrolases;Goals;Growth;Immune;Immune system;In Vitro;in vivo;Infection;lethal factor;Lytic;lytic replication;Metagenomics;Modeling;Monitor;overexpression;pathogenic bacteria;Population;Process;Prokaryotic Cells;protein metabolism;Protein Overexpression;Proteins;Reaction;repaired;Replication-Associated Process;Research;response;Single-Stranded DNA;small molecule;SS DNA BP;Surveys;System;tool;Toxin;Viral;viral DNA;Virus Diseases

PROJECT_TITLE: Activation of the anti-phage defense DarTG by infected E. coli


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Maternal Health;Maternal Morbidity and Mortality;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: BERKELEY

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROJECT NARRATIVE This study will be the first to examine risk of future diabetes after elevated glycemia levels during pregnancy by racial/ethnic groups and disaggregated subgroups, as well as the modification of this risk by neighborhood level deprivation. It will also expand our understanding of how the community midwifery model of care can support women with elevated glycemia levels during the critical perinatal period to lower their future diabetes risk. This research will promote health equity by generating novel evidence to explain increased diabetes risk among vulnerable populations of birthing people and inform culturally tailored, targeted, neighborhood and clinical interventions to reduce this risk, both fundamental steps toward reducing diabetes related excess mortality and morbidity among individuals of color.

PI_NAMEs: PARIMI, MOUNIKA  (contact)

PROJECT_TERMS: Address;Affect;Age;Asian;Asian Americans;Birth;Blood Pressure;Caring;Clinical;clinical practice;cohort;Color;Communities;Continuity of Patient Care;Data;deprivation;Development;Diabetes Mellitus;diabetes risk;Diagnosis;Diagnostic;Diagnostic tests;Dimensions;Disparity;Disproportionately impacts women;economic disparity;Environment;ethnic disparity;ethnic minority;ethnic minority population;Ethnic Origin;Ethnic Population;Excess Mortality;Future;Gestational Diabetes;Glucose Intolerance;Goals;Health;health equity promotion;high risk;Hispanic;holistic approach;improved;indexing;Individual;Inequity;Integrated Health Care Systems;Intervention;Interview;Knowledge;Learning;Life Style;Measures;Methods;Midwife;Midwifery;Modeling;Modification;Morbidity - disease rate;mortality;National Institute of Diabetes and Digestive and Kidney Diseases;neighborhood disadvantage;Neighborhoods;Non-Insulin-Dependent Diabetes Mellitus;novel;Nutritional;Obesity;Outcome Study;Pathway interactions;people of color;Perinatal Care;perinatal intervention;perinatal outcomes;perinatal period;Persons;Pharmacologic Substance;Play;poor health outcome;population based;postpartum care;Postpartum Period;Pregnancy;pregnant;prevent;Prevention;Process;programs;Race;racial disparity;racial minority;racial minority population;racial population;Reduce health disparities;Research;Resources;Risk;Risk Factors;screening;social determinants;social health determinants;Social support;sociodemographics;Strategic Planning;Subgroup;Test Result;Testing;Translating;United States;Visit;Vulnerable Populations;Woman;women of color;Work

PROJECT_TITLE: Addressing racial and ethnic disparities in diabetes risk after varying glycemia levels during pregnancy


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Aging;Arthritis;Nutrition;Obesity;Osteoarthritis;Physical Injury - Accidents and Adverse Effects

ORG_CITY: PHILADELPHIA

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE  Meniscus tears are among the most common knee injuries and lead to osteoarthritis, especially in patients with metabolic risk factors like obesity. The goal of this project is to elucidate how signals from adipose tissue influence meniscus cell response to homeostatic and injury-associated mechanical cues. Our results will establish the basis for mechanical-metabolic interactions in meniscus health and degeneration, providing insight towards novel meniscus repair strategies in high-risk patients.

PI_NAMEs: KUPRATIS, MEGHAN ELIZABETH (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Actins;Acute;Address;adipokines;Adipose tissue;Adult;Aging;articular cartilage;Attenuated;attenuation;Behavior;Biomechanics;Calcium;cartilage degradation;Catabolism;Cell Physiology;cell type;Cells;Connective Tissue;Cues;Cytoskeleton;Degenerative polyarthritis;Development;Disease;Dyslipidemias;early onset;Excision;Extracellular Matrix;Foundations;Functional disorder;Gene Expression;Generations;Goals;healing;Health;Heterogeneity;high risk;Homeostasis;Hyperglycemia;Hypertension;Impairment;Inflammation;Inflammatory;Injury;insight;Joints;Knee;Knee Injuries;Knee joint;Knee Osteoarthritis;Knowledge;Link;mechanical properties;mechanical signal;Mechanics;Mediating;Mediator;Memory;meniscal tear;meniscus injury;Meniscus structure of joint;Mesenchymal;Metabolic;Metabolic syndrome;Modeling;Morphology;Multiscale Mechanics;Musculoskeletal;nanoscale;new therapeutic target;novel;Nuclear;Nuclear Translocation;Obesity;Operative Surgical Procedures;Pathogenesis;Pathologic;Patients;Pattern;Phenotype;Physiological;Population;preclinical study;Production;programs;Proteoglycan;regenerative approach;Regulation;repair strategy;repaired;Research;response;response to injury;Risk;Risk Factors;Role;scaffold;Secondary to;Signal Transduction;soft tissue;Stress Fibers;Structure;Synovitis;System;Techniques;Tendon structure;Testing;Tissue Engineering;Tissues;Traction Force Microscopy;Training;transmission process;Weight-Bearing state;Work

PROJECT_TITLE: Multiscale mechano-metabolic regulation of fibrous tissue homeostasis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10B-Q (20)]


ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Immunecheckpoint inhibitors are the most common type of immunotherapy used for treatment of a large variety of cancers and can lead to long-term remissions in responder patients by boosting their anti-tumor T cell immune response, but it is becoming clear that they can also cause long-term adverse effects in a relative high frequency due to an unleashed systemic immune response. There is a major need to identify who is at a higher risk to develop these immune related adverse events (irAE) and how to manage these effects as part of personalized medicine. We propose to examine genetic polymorphisms in the IL-6 and IL-6R genes that can make CD4 T cells from cancer patients to produce higher levels of this cytokine and to cause damage of different tissues through their response to IL-6.

PI_NAMEs: RINCON, MERCEDES  (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Achievement;Address;Adverse effects;Adverse event;Affect;Aftercare;Attention;Binding;Blocking Antibodies;Cancer Etiology;cancer immunotherapy;Cancer Patient;cancer therapy;cancer type;Cardiac Myocytes;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell surface;Cells;Code;CTLA4 gene;cytokine;Data;Dendritic Cells;Dermatologic;Development;Disease;Disease remission;Endocrine;Endothelial Cells;Exploratory/Developmental Grant;FDA approved;Fibroblasts;Frequencies;gastrointestinal;Genes;Genetic;Genetic Polymorphism;Genetic Predisposition to Disease;Haplotypes;healthy volunteer;Hepatocyte;high risk;Human;IL6 gene;IL6 Signaling Pathway;IL6ST gene;immune checkpoint;Immune checkpoint inhibitor;Immune response;immune-related adverse events;Immunotherapeutic agent;Immunotherapy;Incidence;Inflammatory;inhibitor;inhibitor therapy;Innate Immune System;interest;Interleukin-6;Leukocytes;Life;Lung;Macrophage;Malignant Neoplasms;Mediating;Mediator;Metalloproteases;Mus;Neurons;novel;novel strategies;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;personalized medicine;Production;programmed cell death protein 1;promoter;Quality of life;response;Risk;Role;Serum;Signal Transduction;T-Lymphocyte;Terminally Ill;Tissues;tocilizumab;Toxic effect;tumor

PROJECT_TITLE: IL-6 and IL-6R genetic polymorphisms in immune-related adverse events caused by cancer immunotherapy

STUDY_SECTION: TIR

STUDY_SECTION_NAME: Therapeutic Immune Regulation Study Section[TIR]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alcoholism, Alcohol Use and Health;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;Cerebrovascular;Dementia;Lymphatic Research;Machine Learning and Artificial Intelligence;Neurodegenerative;Neurosciences;Prevention;Substance Misuse

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: Heavy alcohol use can lead to cognitive, emotional, and physical impairments, and eventually culminate in neurodegeneration. Considering that alcohol consumption, especially heavy consumption during middle age, is the strongest modifiable risk factor for Alzheimer’s Disease and related dementias; it is imperative to understand how alcohol use affects health outcomes. This proposal will extensively characterize the behavioral and biological changes that occur with chronic alcohol use across the lifespan in a transgenic mouse model of neurodegeneration.

PI_NAMEs: PATARINO, MAKENZIE  (contact)

PROGRAM_OFFICER_NAME: AKBAR, MOHAMMED

PROJECT_TERMS: abeta deposition;Acceleration;Acute;Adult;adverse outcome;Affect;Aging;aging population;aging process;aging related;Alcohol consumption;alcohol effect;Alcohols;Algorithms;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease risk;Behavior;behavior prediction;behavior test;Behavioral;behavioral impairment;behavioral outcome;Biological;Biological Markers;blast trauma;Brain;Cell Death;Chronic;chronic alcohol ingestion;Clinical;Clinical assessments;Clinical Research;clinically relevant;Cognitive;Cognitive deficits;combat;Consumption;cytokine;Data;Data Set;Dementia;Development;Diagnosis;Disease;Dose;Emotional;Environment;Ethanol;Female;fluorodeoxyglucose positron emission tomography;glucose metabolism;glymphatic clearance;glymphatic function;Goals;habituation;hallmarks of aging;Health;Heavy Drinking;Image;Immunohistochemistry;Impaired cognition;Impairment;improved;Individual Differences;Inflammation;Injections;insight;Knowledge;life span;Light;Link;Literature;Locomotion;Long-Term Effects;Machine Learning;machine learning algorithm;male;Measures;Metabolism;Methods;microbiome;middle age;Modeling;modifiable risk;Molecular;mouse model;Mus;Nerve Degeneration;Nervous System Trauma;Neurodegenerative Disorders;Neurologic;Neurological outcome;older adult;Outcome;Pathologic;pathological aging;Pathology;Pattern;Peripheral;physical impairment;Population;Positron-Emission Tomography;potential biomarker;Pre-Clinical Model;preclinical study;Prevalence;Reflex action;Research;Research Design;Risk Factors;Sampling;Sedation procedure;Sex Differences;Societies;Survivors;System;tau aggregation;tau expression;tau interaction;tau Proteins;Tauopathies;Techniques;Time;Transgenic Mice;Travel;Water;Wild Type Mouse

PROJECT_TITLE: Uncovering the Synergistic Effects of Chronic Alcohol Use and Pathological Tau Expression


NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Caregiving Research;Clinical Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Prevention

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE The proposed F31 project will investigate how the understanding that words can be referential emerges in early childhood and whether this understanding acts as a mechanism through which infants’ temporally coordinated interactions with caregivers support language development. It will use a sample of infants at elevated likelihood for autism and ADHD, who commonly experience language delays. Findings may inform efforts to detect language difficulties and intervene in a timely, targeted manner.

PI_NAMEs: PIERGIES, ANTONIA  (contact)

PROGRAM_OFFICER_NAME: KAU, ALICE S

PROJECT_TERMS: Affect;Age Months;Attention;Attention deficit hyperactivity disorder;autism spectrum disorder;Behavioral;Caregiver support;Caregivers;Characteristics;Child;Clinical;Clinical Sciences;Code;cognitive development;comparison group;Data;design;Development;Developmental Course;Diagnosis;Diagnostic;dyadic interaction;early childhood;Early Diagnosis;Etiology;experience;Exposure to;Faculty;Family;Family member;gaze;Goals;Growth;Infant;Intervention;Knowledge;Language;Language Delays;Language Development;language outcome;Life;Longitudinal Studies;Measures;Mediating;Mediation;Mediator;mental representation;Mentors;Mentorship;Modeling;Monitor;National Institute of Child Health and Human Development;Nature;Neurocognitive;novel;Outcome;Pathway interactions;Phenotype;Population;Positioning Attribute;Prevention strategy;Procedures;Process;protective factors;Psychopathology;Research;Risk;Role;Sampling;Secure;skills;social;standardize measure;tenure track;Testing;Time;Toddler;Training;treatment strategy;visual tracking;Vocabulary;vocalization

PROJECT_TITLE: Examining transdiagnostic mechanisms of language development in infants at elevated likelihood for autism and ADHD

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01B-M (20)]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Gene Therapy;Genetics;Immunotherapy;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PHR: PROJECT NARRATIVE  Adoptive transfer of tumor-targeting T cells has produced remarkable clinical responses against hematologic malignancies, but efficacy in more common solid tumors has been limited in part by rapid dysfunction and poor persistence of infused T cells. Tcf1+ stem-like T cells in tumor-draining lymph nodes maintain persistent and functional T cell responses and are critical for anti-tumor control and response to immunotherapy, but it is not clear whether engineered TCR-T cells are able to form stem-like reservoirs in tumor-draining lymph-nodes and how this impacts their long-term persistence, function, and response to immunotherapy. In this proposal, I will use a clinically relevant model of human lung cancer to define the mechanisms influencing the ability of TCR-T cells to form Tcf1+ stem-like reservoirs in lymph nodes and determine whether vaccination can be used to activate these reservoirs to improve tumor control.

PI_NAMEs: NUTT, WILLIAM SAMUEL (contact)

PROJECT_TERMS: Activities of Daily Living;Address;Adoptive Cell Transfers;Adoptive Transfer;Affect;Antigen Presentation;Antigen Targeting;Antigens;Antitumor Response;ATAC-seq;Basic Science;Biological Assay;Biological Models;Cell Count;Cell Therapy;Cells;cellular engineering;Characteristics;Chronic;Clinic;Clinical;clinically relevant;Data;Defect;Dendritic cell activation;Dendritic Cells;Development;Dose;draining lymph node;engineered T cells;Engineering;epigenetic regulation;exhaust;exhaustion;experimental study;Flow Cytometry;Fluorescence Microscopy;Frequencies;Functional disorder;Gene Expression Regulation;Hematologic Neoplasms;Homing;human disease;human model;Immunofluorescence Microscopy;Immunotherapy;Impairment;improved;In Vitro;in vivo;Infusion procedures;insight;Knowledge;KRASG12D;Label;Lung Adenocarcinoma;lymph nodes;Maintenance;Malignant neoplasm of lung;Mediating;Memory;mesothelin;Modeling;mouse model;Mus;neoantigens;neoplastic cell;novel;novel vaccines;Ovalbumin;overexpression;Ovum;patient response;Patient-Focused Outcomes;PD-1/PD-L1;PD-L1 blockade;Phenotype;Population;pre-clinical research;preservation;Productivity;progenitor;programmed cell death protein 1;response;self-renewal;skills;Solid Neoplasm;Sorting;stem;stemness;success;T cell differentiation;T cell response;T cell therapy;T-Cell Activation;T-Cell Receptor Therapy;T-Lymphocyte;TCR Activation;Testing;Therapeutic;TP53 gene;transcriptome sequencing;Translating;translational scientist;tumor;Tumor Antigens;tumor immunology;tumor microenvironment;Tumor Promotion;Vaccination;vaccine platform;Visualization;Work

PROJECT_TITLE: Improving engineered TCR-T cell therapy for solid tumors by targeting Tcf1+ stem-like reservoirs in tumor-draining lymph nodes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09C-Z (20)]


NIH_SPENDING_CATS: Biotechnology;Congenital Structural Anomalies;Genetics;Pediatric;Prevention;Stem Cell Research;Stem Cell Research - Embryonic - Human

PHR: PROJECT NARRATIVE In the United States, congenital malformations and deformations are the leading cause of death in infants. The proposed research aims to uncover novel gene regulatory interactions that specify cell identities during normal development. The objective of this study is to use human pluripotent stem cells to how cell identities are specified, with the ultimate goal to inform new strategies for the treatment and prevention of congenital disorders.

PI_NAMEs: PARK, EMILY J (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Address;Affect;Area;Automobile Driving;Binding;Binding Proteins;career;career networking;Cause of Death;Cell Differentiation process;Cell Fate Control;cell fate specification;Cell Nucleus;cell transformation;Cells;Child Development;Chromatin;chromatin protein;Cleavage Under Targets and Release Using Nuclease;Clinical;clinical training;college;Communication;Complex;Congenital Abnormality;Congenital Disorders;CRISPR interference;Data;design;Development;developmental disease;Developmental Gene;directed differentiation;Disease;DNA;DNA Binding;Doctor of Medicine;Doctor of Philosophy;Ectoderm;Embryo;embryo cell;Embryoid bodies;Endoderm;Environment;epigenetic silencing;experience;EZH2 gene;Feedback;Fellowship;Fetal Development;Fostering;gastrointestinal;gastrulation;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Germ Layers;Goals;Growth;Human;Human Development;human induced pluripotent stem cells;human pluripotent stem cell;human stem cells;Impairment;improved;in silico;in vitro Model;Infant Mortality;insight;Knowledge;Lead;Learning;Maintenance;Mediating;Medical center;Medical Research;Medicine;Mesoderm;Messenger RNA;Molecular;Mutate;novel;novel strategies;novel therapeutic intervention;pediatrician scientist;Pediatrics;Physicians;Physiological;Play;pluripotent stem cell differentiation;Post-Transcriptional Regulation;posttranscriptional;prevent;Prevention;programs;protein expression;Protein Isoforms;Regulation;Regulator Genes;Research;RNA;RNA Binding;RNA Processing;RNA Splicing;RNA-Binding Proteins;Role;Scientist;skills;Specific qualifier value;stem cell fate specification;stem cells;System;Testing;Texas;Therapeutic;three dimensional structure;Time;tool;Training;Transcript;Transcription Process;Transcriptional Regulation;transcriptome;transcriptomics;United States

PROJECT_TITLE: Defining the role of ILF2-ILF3 in human cell fate

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


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Conditions Affecting the Embryonic and Fetal Periods;Fetal Alcohol Spectrum Disorders (FASD);Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Substance Misuse

ORG_CITY: LOS ANGELES

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE While fetal ethanol exposure causes a well-described complex of conditions, there is also mounting evidence and concerns that some outcomes, including neurobehavioral changes, are also detectable in the third generation following initial exposure. However, how a memory of ethanol exposure persists across generations is currently not well understood. My work will identify the epigenetic underpinnings of ethanol’s transgenerational neurobehavioral effects, which will lay out a strong foundation for the implication of these pathways in a human context.

PI_NAMEs: FILIPOWICZ, ADAM RICHARD (contact)

PROGRAM_OFFICER_NAME: LORANG-LEINS, DOMINIQUE

PROJECT_TERMS: Acetylation;Address;Adult;Affect;alcohol behavior;Alcohol consumption;alcohol effect;alcohol exposure;alcohol memory;alcohol research;alcohol response;alcohol seeking behavior;Alcohol withdrawal syndrome;Alcohol-Related Neurodevelopmental Disorder;Alcohols;Animal Model;Animals;Applied Genetics;Automobile Driving;Behavior;Behavioral;Behavioral Assay;Behavioral Genetics;Biological Assay;Biological Models;Brain;Caenorhabditis elegans;career;Cell Nucleus;Chemical Exposure;cholinergic;Cleavage Under Targets and Release Using Nuclease;Cognitive;Collection;Complex;Congenital Abnormality;Data;Dose;Environment;Environmental Exposure;epidemiological model;epigenetic memory;Epigenetic Process;epigenome;epigenomics;Ethanol;Ethanol Metabolism;fetal;Fetal alcohol effects;Fetal Alcohol Exposure;Fetal Alcohol Spectrum Disorder;Fetal Alcohol Syndrome;Foundations;Future;Generations;Genes;Genetic;genetic manipulation;Genome;Genomics;Glutamates;Goals;Histone Acetylation;histone acetyltransferase;histone demethylase;Histones;Hour;Human;Immunofluorescence Immunologic;Knowledge;Larva;Mammals;Mediating;Memory;Mentors;Metabolic Pathway;Methods;model organism;Modeling;Modification;mouse model;multiplex assay;Nematoda;Nervous System;neurobehavioral;neurobehavioral disorder;Neurobiology;Neurologic;Neurologic Effect;neuronal circuitry;Neurons;Organism;Outcome;Pathway interactions;pharmacologic;prenatal exposure;programs;Provider;Quantitative Reverse Transcriptase PCR;Research;RNA Interference;Rodent;Rodent Model;Role;Running;Sorting;Study models;Testing;Training;transmission process;Validation;Work

PROJECT_TITLE: Neuroepigenetic mechanisms of alcohol response


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Brain Disorders;Drug Abuse (NIDA only);Neurosciences;Substance Misuse

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Narrative  This research application is focused on the structure and function of GABAA receptors, which are neurotransmitter receptors critical for regulating central nervous system function. They are major drug targets for treating anxiety, insomnia and convulsive disorders, and for induction and maintenance of anesthesia. The proposed studies will elucidate how therapeutics and drugs of abuse interact with this important class of cell surface receptors, how the receptors signal, and how they are assembled, providing essential information for improved therapeutics targeting these receptors.

PI_NAMEs: HIBBS, RYAN E (contact);NAUEN, DAVID W

PROGRAM_OFFICER_NAME: ANANTHAN, SUBRAMANIAM

PROJECT_TERMS: abuse liability;access restrictions;Address;Adopted;Agonist;Anesthesia procedures;Anesthetics;Anti-Anxiety Agents;anti-depressive agents;Anxiety;Anxiety Disorders;Area;Barbiturates;Benzodiazepines;Binding;Binding Sites;Biological Assay;Brain;Brain Diseases;Brain region;brain tissue;Categories;Cell Surface Receptors;Central Nervous System;Chemosensitization;Clinic;Clinical;Complex;Computer Analysis;Coupled;Cryoelectron Microscopy;Data;desensitization;design;Diazepam;Disease;Dormutil;Drug abuse;Drug Binding Site;drug development;drug of abuse;Drug Targeting;Electrophysiology (science);Environment;Epilepsy;Equilibrium;Ethanol;excitotoxicity;Family;Freezing;Functional disorder;GABA-A Receptor;gamma-Aminobutyric Acid;General anesthetic drugs;Grant;Human;hypnotic;improved;Individual;insight;interdisciplinary approach;Investigation;Ion Channel Gating;Knowledge;Maintenance;Maps;Medical;Methaqualone;Modeling;Molecular Conformation;molecular dynamics;Nervous System Physiology;neurosteroids;Neurotransmitter Receptor;Neurotransmitters;Nicotinic Receptors;Pattern;Personal Satisfaction;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phenobarbital;photolysis;Population;Predisposition;Propofol;Publishing;receptor;Receptor Signaling;Recombinants;Research;Rest;Schedule;sedative;Seizures;sevoflurane;Signal Transduction;Sleeplessness;structural biology;Structure;success;Synapses;System;targeted treatment;Techniques;technology development;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;three dimensional structure;Time;Tissues;Visualization;Volatilization;Work;zolpidem

PROJECT_TITLE: Structure and Function of GABA-A receptors

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MBBC-K (02)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: PROJECT NARRATIVE Degeneration of neuronal axons occurs after acute nerve injury and in several neuropathological conditions, including chronic neuropathies. Several proteins that control axon degeneration are modified with a lipid called palmitate, a process called palmitoylation. The proposed research will define the importance of palmitoylation for axon degeneration and could reveal new therapeutic strategies to prevent axon degeneration in a wide range of neuropathologies and thereby benefit human health.

PI_NAMEs: HESKETH, NATASHA LOUISE (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Acute;Address;Affect;Alanine;Axon;axon injury;axonal degeneration;Axonal Transport;Bioinformatics;Biological;Biological Assay;Biotin;Cell Separation;cell type;Cells;Cellular biology;Chronic;Cultured Cells;Data;Data Set;Development;Distal;Ensure;Enzymes;Event;experimental study;Family;fast axonal transport;follow-up;Genetic;Glutamate-ammonia-ligase adenylyltransferase;Health;Human;Hydrolase;improved;in vivo;inhibitor;Injury;insight;knock-down;Knock-in;Knock-in Mouse;Lightning;Lipids;MAPK8 gene;Maps;Mediating;Modification;Mus;mutant;Mutate;N-terminal;Nerve Degeneration;nerve injury;Neurodegenerative Disorders;Neuroglia;neuronal cell body;Neurons;neuropathology;Neuropathy;new therapeutic target;Nicotinamide Mononucleotide;novel;novel therapeutic intervention;novel therapeutics;Palmitates;palmitoylation;Pathologic;Peripheral Nervous System Diseases;pharmacologic;Phenocopy;Phosphorylation;Phosphorylation Site;Phosphotransferases;Physiological;Pilot Projects;Play;prevent;Process;Protein Inhibition;Proteins;Proteomics;Regulation;Research;Resistance;Role;Site;slow potential;small hairpin RNA;Spinal Ganglia;Spottings;Transfection;Vesicle;Viral;Wallerian Degeneration;Wild Type Mouse;Work

PROJECT_TITLE: Control of Axon Degeneration by Palmitoylation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03A-E (20)]


NIH_SPENDING_CATS: Cancer;Genetics;Lung;Lung Cancer

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Some cancer therapies can kill cancer cells via ferroptosis, an oxidative form of cell death. The stress- responsive transcription factor nuclear factor erythroid 2 like 1 (NFE2L1, or NRF1) protects cancer cells from ferroptosis. The proposed aims seek to elucidate the mechanism by which NFE2L1 confers ferroptosis resistance to better understand and target cancer therapy resistance.

PI_NAMEs: MURRAY, MAGDALENA  (contact)

PROJECT_TERMS: Academia;Adenocarcinoma Cell;Amino Acid Sequence;Antioxidants;Asparagine;Aspartate;Aspartic Endopeptidases;Automobile Driving;Biochemical;biological adaptation to stress;cancer cell;Cancer cell line;Cancer Patient;cancer therapy;career;Cell Death;Cell Line;Cell Therapy;Cells;Cessation of life;ChIP-seq;Cleavage Under Targets and Release Using Nuclease;Cytosol;Data;design;DNA Damage;Endoplasmic Reticulum;Enzymes;Event;experimental study;Genes;Genetic;Glycobiology;glycosylation;Goals;Homeostasis;Homologous Gene;Immunotherapy;improved;insight;Ionizing radiation;Kinetics;Knock-out;Learning;Lipid Peroxidation;Lung Adenocarcinoma;lung cancer cell;Mass Spectrum Analysis;Measures;Mediating;Mentors;Metabolism;metabolomics;Molecular;mortality;mutant;Nicotinamide adenine dinucleotide;Nicotinamide N-Methyltransferase;novel;nuclear factor-erythroid 2;Nuclear Translocation;overexpression;Oxidation-Reduction;Pathway interactions;Peptide N-Glycosidase;pharmacologic;Play;Post-Translational Protein Processing;professor;Regulation;Research;Resistance;resistance mechanism;Role;Stress;targeted cancer therapy;Technical Expertise;Techniques;Testing;therapeutically effective;therapy resistant;tool;Training;transcription factor;transcriptome sequencing;Universities;Up-Regulation;Variant;Western Blotting

PROJECT_TITLE: Investigating the regulation of cancer cell death by NFE2L1

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09A-R (20)]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Estrogen;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences;Rare Diseases;Women's Health Research

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE This proposal investigates the molecular and transcriptional basis for how systemic circulating sex hormones are responsible for increased photoreceptor cell degeneration in a preclinical mouse model of Retinitis Pigmentosa, a group of devastating visual disorders leading to blindness. Specifically, I aim to determine how estrogen and progesterone signal through receptors in the retina to increase the photoreceptor stress responses and programmed cell death pathways. The results from this work will provide critical insight into treatment and monitoring strategies for male and female patients with these diseases, as well as potential approaches for future therapeutics targeting the sex hormone pathways in the retina during retinal degenerative disease.

PI_NAMEs: ROWE, ASHLEY  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Acceleration;Address;Affect;Agonist;antagonist;Apoptosis;Apoptotic;Area;autosome;biological adaptation to stress;Biological Models;biological sex;Blindness;career;Caspase;Cause of Death;Cell Death;Cell Physiology;Cellular Stress;Cessation of life;Clinical;Disease;Disease Progression;endoplasmic reticulum stress;Estrogens;experimental study;Female;Future;Gene Expression;Genetic;Genetic Transcription;Goals;Gonadal Steroid Hormones;Health;Hormonal;hormonal signals;Hormone Receptor;hormone therapy;Hormones;in vivo;insight;Investigation;male;Measures;Mediating;Molecular;Molecular Biology Techniques;Molecular Target;Monitor;mouse model;Mus;Neurodegenerative Disorders;neurodegenerative phenotype;Neurons;novel;Nuclear Receptors;Operative Surgical Procedures;Outcome;Ovariectomy;Pathway interactions;Patients;Pharmaceutical Preparations;photoreceptor degeneration;Photoreceptors;pre-clinical;Progesterone;Proteins;receptor;Research;Research Personnel;response;Retina;Retinal Degeneration;Retinal Diseases;Retinitis Pigmentosa;Rhodopsin;Role;Safety;Sex Differences;sexual dimorphism;Signal Transduction;Signs and Symptoms;skills;Testing;therapeutic target;transcriptome sequencing;Vision Disorders;Visual;women patients;women versus men;Work

PROJECT_TITLE: Investigating the Role of Systemic Sex Hormones on Photoreceptor Degeneration